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  • 1.
    Alping, P.
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; Karolinska Institutet, Clinical Epidemiology Division, Department of Medicine Solna, Stockholm, Sweden.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Fink, K.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; Stockholm Health Services, Academic Specialist Centre, Stockholm, Sweden.
    Fogdell-Hahn, A.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Hillert, J.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; Karolinska University Hospital, Department of Neurology, Stockholm, Sweden.
    Langer-Gould, A.
    Kaiser Permanente, Clinical and Translational Neuroscience, Southern California Permanente Medical Group, Pasadena, United States.
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden.
    Nilsson, P.
    Lund University, Department of Clinical Sciences/Neurology, Lund, Sweden.
    Olsson, T.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; Stockholm Health Services, Academic Specialist Centre, Stockholm, Sweden.
    Salzer, J.
    Department of Clinical ScienUmeå University, Department of Pharmacology and Clinical Neuroscience, Umeå, Sweden.
    Svenningsson, A.
    Karolinska Institutet, Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Vrethem, M.
    Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Frisell, T.
    Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Piehl, F.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Effectiveness of initial MS treatments in the COMBAT-MS trial: injectables, dimethyl fumarate, natalizumab and rituximab2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr Suppl. 2, s. 21-22Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Direct comparisons across multiple disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) are valuable in clinical decision making. COMBAT-MS (NCT03193866) is an observational drug trial capturing data on clinical relapses, lesions on magnetic resonance imaging (MRI), Expanded Disability Status Scale (EDSS), and drug survival, at all Swedish university clinics.

    Objective: Compare the effectiveness of the most common initial MS therapies in Sweden.

    Methods: All first-ever MS treatments with injectables (INJ, interferon-β/glatiramer acetate), dimethyl fumarate (DMF), natalizumab (NTZ), and rituximab (RTX), started 2011-01-01 to 2020-12-14, were identified with prospectively recorded outcome data in the Swedish MS Register. Follow-up continued even if the therapy ended. Missing data were imputed using multiple imputation and potential confounding was adjusted for using stabilized inverse probability of treatment weighting with baseline variables: age, sex, MS duration, geographical region, EDSS, and relapses. All comparisons are made against RTX.

    Results: We included 1936 first-ever therapy episodes: 856 INJ, 341 DMF, 270 NTZ, and 469 RTX. Baseline characteristics differed by DMT, with natalizumab having the youngest patients, shortest MS duration, and the most previous relapses.After adjustment, the hazard ratio (HR) for first relapse vs RTX was for INJ 5.9 (95% confidence interval 3.7; 9.5), DMF 2.8 (1.7; 4.8), and NTZ 1.8 (1.0; 3.3). Similarly, the relative three-year lesion rate was for INJ 6.06 (3.75; 9.80), DMF 3.52 (2.01; 6.17), and NTZ 2.03 (1.14; 3.64). EDSS differences at three years were only marginally different: INJ 0.25 (0.06; 0.44), DMF 0.05 (-0.16; 0.26), and NTZ 0.00 (-0.23; 0.24). In contrast, HR for treatment discontinuation was marked: INJ 32.5 (19.0; 55.7), DMF 20.2 (11.5; 35.4), and NTZ 16.2 (8.9; 29.5).

    Conclusions: In treatment-naïve patients, RTX was associated with the lowest risk of relapses and MRI lesions, and by far the lowest probability of switching to a second therapy. In contrast, EDSS at 3 years was similar for RTX, DMF, and NTZ, and only slightly higher for INJ. The apparent difference in effectiveness between NTZ and RTX could possibly be explained by the vulnerable period after switching from NTZ, mainly due to JC virus positivity. These findings underscore the importance of tracking long-term outcomes from first DMT start, while considering subsequent therapy switches.

  • 2.
    Anna Karin, Hedström
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Stenberg, Erik
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of surgery.
    Tim, Spelman
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lars, Forsberg
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Erik, Näslund
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Jan, Hillert
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    The impact of bariatric surgery on disease activity and progression of multiple sclerosis: A nationwide matched cohort study2022Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, nr 13, s. 2099-2105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Surgical outcomes in patients with multiple sclerosis (MS) following metabolic surgery appear to be similar compared to those of the general bariatric population.

    OBJECTIVE: To study the impact of metabolic surgery on the clinical course of MS.

    METHODS: Using data from the Scandinavian Obesity Surgery Registry and the Swedish Multiple Sclerosis register, we compared disease outcomes in 122 cases of MS who had undergone metabolic surgery with those of 122 cases of MS without surgery, matched by a two-staged Propensity score match, including age at disease onset, sex, MS phenotype, body mass index, and preoperative severity of MS as measured by the Expanded Disability Status Scale.

    RESULTS: The time to 6-month confirmed disability progression during the first five years postbaseline was shorter among the surgical patients (hazard ratio (HR) = 2.31, 95% confidence interval (CI) = 1.09-4.90; p = 0.03). No differences were observed regarding postoperative annual relapse rate (p = 0.24) or time to first postoperative relapse (p = 0.52).

    CONCLUSION: Although metabolic surgery appears to be a safe and efficient treatment of obesity in patients with MS, the clinical course of the disease might be negatively affected. Long-term nutritional follow-up after surgery and supplementation maintenance are crucial, particularly among those with preoperative deficits.

  • 3.
    Axelsson, Markus
    et al.
    University of Gothenburg, Gothenburg, Sweden .
    Malmeström, Clas
    University of Gothenburg, Gothenburg, Sweden .
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län.
    Zetterberg, Henrik
    University of Gothenburg, Mölndal, Sweden; Institute of Neurology, The University College London (UCL), London, UK.
    Sundstrom, Peter
    Umeå University, Umeå, Sweden .
    Lycke, Jan
    University of Gothenburg, Gothenburg, Sweden .
    Svenningsson, Anders
    Umeå University, Umeå, Sweden .
    Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis2014Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 1, s. 43-50Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression.

    Objective: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13).

    Methods: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays.

    Results: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline.

    Conclusions: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.

  • 4.
    Biström, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Andersen, O.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Alonso-Magdalena, L.
    Department of Neurology, Skåne University Hospital, Malmö, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Hultdin, J.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    High serum concentrations of vitamin D may protect against multiple sclerosis2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 1001-1002Artikel i tidskrift (Övrigt vetenskapligt)
  • 5.
    Biström, M.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Hultdin, J.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Andersen, O.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Alonso-Magdalena, L.
    Department of Neurology, Skåne University Hospital, Malmö, sweden.
    Jons, D.
    Department of Clinical Neuroscience, Institution of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Vrethem, M.
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Sundström, P.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Leptin levels are associated with multiple sclerosis risk2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 904-904Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: One environmental factor that in the last decade repeatedly has been linked to increased risk of developing multiple sclerosis (MS) is overweight, including obesity, early in life. The incidence of both MS and overweight are increasing, making elucidation of this connection important. The adipokine leptin is strongly correlated to both body mass index and total fat mass and the peptide hormone insulin is associated with obesity and type 2 diabetes, making leptin and insulin suitable biomarkers to investigate the connection between overweight and MS.

    Objectives: To determine if leptin or insulin are risk factors for developing relapsing MS.

    Aims: To further the understanding of how overweight influence MS risk.

    Methods: In this case-control study, we compared concentrations of leptin and insulin in 649 individuals that later developed relapsing-remitting MS with 649 matched controls. Cases were matched for biobank, sex, date of sampling and age with decreasing priority. Only prospectively collected samples from individuals below the age of 40 were included in the study. Conditional logistic regression was performed on log10 transformed and z-scored values for the entire group, separately for men and women and divided into age groups.

    Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals below 20 years of age (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.9) and for all men (OR 1.4, 95% CI 1.0–2.0). In contrast, for women aged 30-39 years there was a lower risk of MS with increased leptin levels (OR 0.74, 95% CI 0.54–1.0) when adjusting for insulin levels. No statistically significant association was found between insulin levels and MS risk.

    Conclusions: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals. The age dependent relationship between leptin and MS risk in women - for whom leptin levels are several-fold higher than in men - suggests a possible role for leptin as being the link between MS risk and being overweight early in life.

  • 6.
    Biström, Martin
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Hultdin, Johan
    Clinical Chemistry, Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Alonso-Magdalena, Lucia
    Department of Neurology, Skåne University Hospital, Malmö, Sweden/Lund and Institution of Clinical Sciences, Neurology, Lund University, Malmö, Sweden.
    Jons, Daniel
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Vrethem, Magnus
    Division of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Sundström, Peter
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Leptin levels are associated with multiple sclerosis risk2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr 1, s. 19-27Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Obesity early in life has been linked to increased risk of developing multiple sclerosis (MS). Leptin and insulin are both associated with obesity, making them suitable candidates for investigating this connection.

    OBJECTIVE: To determine if leptin and insulin are risk factors for relapsing-remitting multiple sclerosis (RRMS).

    METHODS: -scored values to calculate odds ratios (ORs) with 95% confidence intervals (CIs).

    RESULTS: -score increase was associated with increased risk of MS in individuals younger than 20 years (OR = 1.4, 95% CI = 1.1-1.9) and in all men (OR = 1.4, 95% CI = 1.0-2.0). In contrast, for women aged 30-39 years, there was a lower risk of MS with increased leptin levels (OR = 0.74, 95% CI = 0.54-1.0) when adjusting for insulin levels.

    CONCLUSION: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals.

  • 7.
    Brenner, P.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Burkill, S.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Jokinen, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Umeå University, Umeå, Sweden.
    Moore, A.
    Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland.
    Geissbuehler, Y.
    Quantitative Safety & Epidemiology, Novartis Pharma AG, Basel, Switzerland.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, S.
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro universitet, Institutionen för läkarutbildning. DepDepartment of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Multiple sclerosis and risk of completed and attempted suicide - a national cohort study2015Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr Suppl. 11, s. 23-24Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated.

    Objectives: To estimate attempted suicide and completed suicide risks among MS patients using national registers and to assess if the inverse association of higher-level education with completed suicide is affected by MS.

    Methods: A total of 29,617 Swedish MS patients were identified through the Swedish Patient Register and matched (by birth year, sex, vital status at diagnosis and region) with 296,164 people without MS from the general population. Cox regression estimated hazard ratios (HR) (with 95% confidence intervals) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education level, decade of study entry, and previous suicide attempts.

    Results: The adjusted HR for attempted suicide among MS patients is 2.18 (1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (1.53-2.30). Overall, men were at higher risk of completing suicide, while women were at higher risk of attempting suicide. Higher education is inversely associated with completed suicide among the non-MS cohort with an HR of 0.68, (0.51-0.91), but not among MS patients, where the HR is 1.10, (0.60-2.04). MS patients were less likely to use a violent method than the non-MS cohort.

    Conclusion: MS patients are at higher risk of both attempted and completed suicide, and the risk increase is present in both men and women. Possibly the stress and perceived prognosis associated with an MS diagnosis increases the risk of suicide. MS appears to eliminate the protective association of higher education with completed suicide.

  • 8.
    Burkill, S.
    et al.
    Centre for Pharmacoepidemiology, Karolinska Institute, Stockholm, Sweden.
    Smith, K. A.
    Clinical Epidemiology Division, Karolinska Institute, Stockholm, Sweden.
    Stridh, P.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Kockum, I.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Alfredsson, L.
    Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology and Biostatistics.
    Bahmanyar, S.
    Centre for Pharmacoepidemiology, Karolinska Institute, Stockholm, Sweden.
    MS and the association of the DQB1*0302 allele with pain2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 437-438Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: There is an established association between multiple sclerosis (MS) and pain treatment, in particular neuropathic pain. Murine models have confirmed an association between carriage of the DQB1*0302 allele and development of neuropathic pain-like behavior after peripheral nerve injury. Observational studies in patients with spinal disc herniation identified an association between the DQB1*0302 allele and pain, indicating a possible link in humans. This HLA allele has not been previously investigated for its influence on susceptibility to pain in MS patients.

    Aim: To determine whether the DQB1*0302 genotype is associated with pain in MS patients or member of the general population without MS.

    Methods: Three Swedish studies (EIMS, GEMS and IMSE) were combined in which enrolled MS patients were matched with 1-2 randomly selected individuals without MS by sex, age and region of residence. Register data was obtained and prescriptions for pain and neuropathic pain were identified as proxy measures for pain. Blood samples were collected and genotyped. Individuals were included if genotype data were available (MS=3877, non-MS=4548). Logistic regression had pain medication use as the outcome, to examine associations with genotype, stratified by MS status.

    Results: Homo- or heterozygous MS patients with the DQB1*0302 allele had no significantly increased risk of pain (adjusted OR 1.02, 95% CI 0.85-1.23) or neuropathic pain (OR 1.14, 0.97-1.34) compared with MS patients without the allele. Non-MS comparators carrying at least one allele had an increased risk of pain (OR 1.18, 1.03-1.35). Additionally, a zygosity effect appeared present particularly for women in the non-MS cohort, as homozygous individuals had a higher risk of pain compared with heterozygotes. No association was observed for MS patients.

    Conclusions: The DQB1*0302 allele was associated with increased risk of pain among the non-MS cohort. Zygocity also impacted on pain risk in this cohort, particularly for women. The same was not observed in MS patients, for which no increased risk was detected. In view of previous data, immune functions seem to be involved in the development of pain and the observed associa-tion is likely due to peripheral nerve injuries or peripheral neu-ropathies. The allele was not associated with pain in the MS population, which often stems from CNS lesions.

  • 9.
    Carling, Anna
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. University Healthcare Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Physiotherapy, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Forsberg, Anette
    Örebro universitet, Institutionen för hälsovetenskaper. University Healthcare Research Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskaper. Region Örebro län. University Healthcare Research Centre.
    CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study2017Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 10, s. 1394-1404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Imbalance leading to falls is common in people with multiple sclerosis (PwMS).

    Objective: To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5).

    Methods: A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up.

    Results: Post-intervention, the exercise group showed statistically significant improvement (p = 0.015) in BBS and borderline significant improvement in MS Walking Scale (p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before (p < 0.001; p < 0.004).

    Conclusion: This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.

  • 10.
    Carling, Anna
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Center for Healthcare Science, Örebro County Council, Örebro, Sweden.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    The validity of the 5 and 10 sit-to-stand test2015Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 4, s. 532-532Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: To rise from a sitting to a standing position and to sit down again are categorized as basic transitional movements, and are performed approximately 50 times a day. The sit-to-stand test (STS test) evaluates strength in lower extremities, neuromuscular functions, balance and vestibular function. There are several versions of the test; two examples of these are the 5STS and 10STS tests. For people with multiple sclerosis (MS), only the 5STS test has been validated. A potential difference between the 5STS and 10STS test can be that more repetitions require more muscular endurance and, thus, the 10STS test will reveal impaired muscular endurance more than the 5STS test.

    Aim: The aim was to evaluate the validity for the 5STS and 10STS tests for people with moderate MS.

    Methods: Forty-seven people with MS with a limited (<200 m) but remaining (>20 m) walking ability were included (32 women; 30 secondary and 12 primary progressive MS). The STS tests were slightly modified for safety reasons; instead of crossing arms over the chest, hand support was allowed. Time was taken from the starting position sitting using the command ‘Go’ and stopped when the participant sat down again after completing the 10th standing position. An intermediate time was taken when sitting down after the fifth standing position (5STS test). Validity was evaluated using the timed up and go test (TUG), 10 minute walk test (10MWT), 2 minute walk test (2MWT) and the Berg balance scale (BBS); calculated using Spearman’s rank correlation. Correlations exceeding 0.60 were considered strong.

    Results: Strong correlations (r=0.60–0.70) were found between the 5STS and 10STS test and the TUG, the 10 MWT, the 2MWT and the BBS. The correlation between the 5STS and 10STS test (r=0.86) indicates that the tests measure slightly different abilities. A slightly stronger correlation was found between the 5STS and BBS (r=−0.68) compared to the 10STS and BBS (r=−0.61). The correlations were stronger between the 10STS and the walk tests compared to the 5STS and walk tests. The high correlation between the 10STS and the 2MWT (r=0.70) can possibly be explained by a muscular endurance component.

    Conclusion: Both the 5STS and 10STS test are valid for people with moderate MS but they do not measure the exact same ability

  • 11.
    Castelo-Branco, A.
    et al.
    Real-World Solutions, IQVIA, Solna, Sweden.
    Bengtsson, C.
    Real-World Solutions, IQVIA, Solna, Sweden.
    Piehl, F.
    Karolinska University Hospital, Neurology, Solna, Sweden.
    Minton, N.
    Bristol Myers Squibb, Princeton, United States.
    Afsari, S.
    Bristol Myers Squibb, Princeton, United States.
    Dietz, D.
    Bristol Myers Squibb, Princeton, United States.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Karolinska Institutet, Clinical Epidemiology Division, Stockholm, Sweden; University College London, Department of Epidemiology and Public Health, London, United Kingdom.
    Treatment patterns in patients with multiple sclerosis: a single hospital cohort study in Sweden2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr Suppl. 2, s. 732-732Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: An increasing number of disease-modifying therapies (DMT) for multiple sclerosis (MS) has led to switching between treatments.

    Objectives: In a Swedish MS cohort study, we analysed switching treatment patterns, including prescribed symptomatic medications, before and after an MS diagnosis.

    Methods: A national incident MS cohort diagnosed in 2008–2016 in the Swedish National Patient Register was linked to the national Prescribed Drug Register. A subcohort in the electronic medical records (EMR) of the Karolinska University Hospital was analysed for medication usage.

    Results: Patients with an MS diagnosis in the EMR cohort (n=1289) were identified (female, 68.2%; mean age (standard deviation), 38.8 (12.2) years). Prescribed symptomatic medications in the year before cohort entry included analgesics (23.2%), antidepressants (13.9%), opioids (13.4%), systemic corticosteroids (11.2%), and anxiolytics (10.0%). In the 4 years after cohort entry, medications included analgesics (65.2%), systemic antibacterials (55.9%), anti-inflammatory and antirheumatics (50.1%), antidepressants (34.8%), anxiolytics (21.1%), antiepileptics (19.1%) and ophthalmic drugs (16.6%). Of 1289 patients, 1040 were prescribed a DMT (80.7%). Median time (months, interquartile range) to first usage of new DMTs by age group was 1.71, 0.82–4.30 (<40 years); 1.87, 0.95–7.00 (40–59 years); and 3.96, 1.15–12.16 (⩾60 years). The most common DMTs (n=patients) were first-line (n=1054): interferons (55.9%), rituximab (15.7%), dimethyl fumarate (9.1%), natalizumab (7.4%), glatiramer acetate (7.1%), fingolimod (3.5%); second-line (n=551): rituximab (29.4%), natalizumab (19.4%), dimethyl fumarate (17.6%), fingolimod (16.3%), glatiramer acetate (7.8%), interferons (3.1%), teriflunomide (2.2%); third-line (n=184): rituximab (51.1%), natalizumab (13.0%), interferons (9.8%), fingolimod (9.8%), dimethyl fumarate (6.0%).

    Conclusions: These data indicate high usage of prescribed symp-tomatic medications before and after the MS diagnosis, which may indicate the consequences of prodromal and early sympto-matic MS. Most patients were treated with a DMT within months of diagnosis, with predominant initial use of interferons, and switching to more potent agents in later lines of therapy. Prescribing patterns are changing and expected to evolve further with earlier use of powerful agents.

  • 12.
    de Flon, P.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Söderström, L.
    Unit of Research, Education and Development, Region Jämtland Härjedalen, Östersund, Sweden.
    Laurell, K.
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology and Neurophysiology, Örebro University Hospital, Örebro, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden.
    Changes of cerebrospinal fluid cytokine profile as a result of switching from first line MS-therapies to rituximab2016Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 22, nr Suppl. 3, s. 622-622Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: New treatment strategies in multiple sclerosis provide insights not only in the clinical effects but also, by their differences in mechanisms of action, in the immunopathological mechanisms behind disease activity.

    Objective: This study describes the change in cyto- and chemokine profile over a two-year period in a cohort of patients with clinically stable RRMS after treatment shift from ongoing first-line injectable disease modifying therapy (iDMT), e.g. interferon beta or glatirameracetat, to the anti-CD20 depleting agent rituximab and the differences compared with a cohort of healthy controls.

    Method: CSF from 73 patients with clinically stable RRMS was analysed by an elektrochemiluminiscens-based ELISA for a panel of 22 cytokines before and one and two year after treatment shift to rituximab and compared with 55 healthy controls.

    Results: During the first year of treatment it was a significant reduction (p< 0.005) in levels of IL-6, IL-8, IL-10, IL-12, IL-15, IP-10, MCP-1, MDC, TARC, sICAM, sVCAM and a significant elevation (p< 0,005) in levels of IL-7 and MIP-1b.

    Compared to healthy controls it was a significantly higher (p< 0,005) level of IFN-gamma, IL-6, IL-8, IL-10, IL-12, IL-15, TNF, IP-10, MDC, MIP-1a, MIP-1b, TARC, SAA, sICAM and sVCAM in patients with RRMS before treatment shift. Levels of IL-5 and IL-7 were significantly lower. One year after treatment shift the levels of IFN-gamma, IL-6, IL-7, IL-15, MIP-1a and SAA did not differ significantly between patients with RRMS and healthy controls.

    Conclusion: This study demonstrates significant changes in cyto- and chemokine profile in patients with RRMS after treatment shift from iDMT to rituximab and compared with healthy controls.

  • 13.
    de Flon, Pierre
    et al.
    Department of Neurology, Östersund Hospital, Östersund, Sweden; Neurology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Östersund, Sweden.
    Laurell, Katarina
    Neurology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Östersund, Sweden.
    Söderström, Lars
    Unit of Research, Education and Development, Östersund Hospital, Region Jämtland Härjedalen, Östersund, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden; Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Improved treatment satisfaction after switching therapy to rituximab in relapsing-remitting MS2017Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 23, nr 9, s. 1249-1257Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: New disease-modifying treatment strategies in multiple sclerosis offer possibilities for individualised treatment. In this study, we evaluated patient-reported outcome measures before and after a switch in therapy from first-line injectable treatments to rituximab.

    Method: A total of 75 patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) receiving ongoing first-line injectable treatment at three Swedish centres had their treatment switched to rituximab in this open-label phase II multicentre study. Assessment of treatment satisfaction, patient-perceived impact of the disease on daily life, fatigue, cognitive symptoms and disease progression was performed 3 months before and at the time of the treatment shift and then for a subsequent 2-year period.

    Results: The overall treatment satisfaction rating improved significantly from a mean of 4.8 (scale range: 1-7), while on injectable therapies, to a mean of 6.3 after 1 year of rituximab treatment (p < 0.001). This improvement was sustained after 2 years. There was no significant change in scores for patient-perceived impact of disease, fatigue or disease progression.

    Conclusion: A shift in therapy from first-line injectables to rituximab in a cohort of clinically stable RRMS patients was followed by improved treatment satisfaction. This is clinically relevant as it may influence long-term adherence to immunomodulating therapy.

  • 14.
    Demirbüker, S. Safer
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 701-702Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 5” (IMSE 5) in order to monitor and determine the long-term safety and effectiveness in a real-world setting.

    Objectives: To follow-up the long-term safety and effectiveness of DMF in a real-world setting.

    Methods: MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg) in Sweden. The IMSE 5 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve and effectiveness measures were assessed using the Wilcoxon Signed Rank Test.

    Results: 2010 DMF-treated patients have been included in the IMSE 5 study between March 2014 and April 2018. 73 % were female and the mean age at treatment start was 40.6 years. The mean treatment duration was 22.3 months. 92 % of the patients had RRMS with 2 % missing data on MS phenotype. Most patients switched from interferon and glaimer acetat (41 %) and 24 % of the patients were treatment naïve (13 % were missing data on prior treatment). The overall one year drug survival was 74 % and 889 patients terminated their treatment at some point. Most patients (39 %) switched to rituximab (15 % have no new treatment registered). The most common reason for discontinuation was AEs (53 %) and lack of effect (29 %). 227 (11 %) patients have continued treatment for ≥36 months. In patients treated with DMF continuously for ≥24 months (n=918), significant improvements in mean values at 24 months of treatment compared to mean baseline values have been noted for EDSS (1.9 ± 1.6 to 1.6 ± 1.6, n=196); MSSS (2.5 ± 2.4 to 2.0 ± 2.0, n=145); SDMT (52.6 ± 11.0 to 53.8 ± 11.7, n=315); MSIS-29 Psychological Subscale (26.3 ± 22.8 to 21.8 ± 20.6, n=337); and EQ-5D (0.76 ± 0.23 to 0.81 ± 0.20, n=284).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. A longer follow-up period is needed to assess the real-world effectiveness and safety of DMF.

  • 15.
    Demirbüker, S. Safer
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of teriflunomid (IMSE 4)2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 922-923Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Teriflunomid (TFM) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology 4” (IMSE 4) in order to surveille and determine the long-term safety and effectiveness in a real-world setting.

    Objectives: To follow-up the long-term safety and effectiveness of TFM in a real-world setting.

    Methods: MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg) in Sweden. The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve.

    Results: 481 TFM-treated patients have been included in the IMSE 4 study between March 2014 and April 2018. 70 % were female and the mean age at treatment start was 45.8 years. The mean treatment duration was 20.5 months. 89 % of the patients had RRMS with 3 % missing data on MS phenotype. Most patients switched from interferon and glatimer acetat (37 %) and 14 % of the patients were treatment naïve before starting TFM. The overall one year drug survival rate was 81 % and the overall two year drug survival rate was 41 %. 168 (35 %) patients terminated their treatment at some point, of which 33 % started rituximab treatment and 22 % have no new treatment registered. The most common reasons for discontinuation were AEs (49 %) and lack of effect (40 %). 318 patients have been continuously treated with TFM for ≥12 months and mean baseline values compared to val-ues at 12 months have been noted for EDSS (2.0 ± 1.5 to 2.2 ± 1.5, n=141); MSSS (2.6 ± 2.2 to 2.9 ± 2.3, n=126); SDMT (50.8 ± 10.5 to 50.8 ± 10.7, n=165); MSIS-29 Physiological subscale (20.2 ± 19.3 to 19.7 ± 20.0, n=181); MSIS-29 Psychological subscale (28.1 ± 22.2 to 23.7 ± 21.7, n=181); EQ-5D (0.74 ± 0.24 to 0.73 ± 0.26, n=154); and VAS (70.0 ± 20.8 to 70.8 ± 19.6, n=150).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. However, a longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.

  • 16.
    Edström, Måns
    et al.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Sweden.
    Mellergård, J.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Neurology, Linköping University, Sweden.
    Mjösberg, J.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Sweden.
    Jenmalm, M. C.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Sweden; Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Paediatrics, Unit of Autoimmunity and Immune Regulation Linköping University, Sweden.
    Vrethem, M.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Neurology, Linköping University, Sweden.
    Press, R.
    Department of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden.
    Dahle, C.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Neurology, Linköping University, Sweden.
    Ernerudh, J.
    Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Sweden.
    Transcriptional characteristics of CD4+ T cells in multiple sclerosis: Relative lack of suppressive populations in blood2011Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, nr 1, s. 57-66Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors.

    Objective: The aim of this study was to assess the balance of CD4(+)T cell populations in relapsing-remitting MS.

    Methods: Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers.

    Results: In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4(+)CD25(hi)Treg. Immunoregulatory EBI3 and Th2-associated GATA3 ([a-z]+) was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005).

    Conclusion: Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4(+)phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.

  • 17.
    Ekström, E.
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Rosengren, V.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Kågström, S.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Forsberg, L.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Berglund, A.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Hillert, J.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, P.
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, C.
    Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Landtblom, A. -M
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Sundström, P.
    Umeå University, Clinical Science, Neurosciences, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, F.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, T.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Real-world longitudinal data of peginterferon beta-1a from the Swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr Suppl. 2, s. 626-627Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. Phase II and III studies have shown that PegIFN reduces relapse rate and disability progression. PegIFN were included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 6) due to the importance of studying the long-term safety and effectiveness.

    Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting.

    Methods: Data was obtained from the Swedish Neuro Registry (NeuroReg). All clinical measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: 393 patients (78% female; 86% RRMS) were included in IMSE 6 between June 2015 and April 2021. Mean age at treatment start was 42 years, mean treatment duration was 23 months. 25% were treatment naïve and 47% switched from other injectables prior PegIFN. The one- and two-year drug survival rate was 58% and 41% respectively, and 31% overall. In total, 271 patients discontinued their PegIFN treatment at some time point, mainly due to adverse events (51%) and lack of effect (26%). Most patients switched to rituximab (37%). During the entire treatment period 54% were relapse-free and 8% had only one relapse (36% missing data). In patients treated at least 24 months tendencies of improve-ments were seen for SDMT and EQ-5D. MSIS-PSYCH showed significantly worsened results (21.2 ± 18.6 to 24.3 ± 19.3, n=46). EDSS, MSSS, MSIS-PHYS and VAS scores remained stable. 25 adverse events (AEs) have been reported to Swedish Medical Product Agency (MPA). 6 of these were classified as serious where general disorders and administration site, and skin (33% respectively) were the most common categories. General disorders and administration site were also the most common for non-serious AEs (68%).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform. All clinical effectiveness measures, except MSIS-PHYS, remained stable in patients treated for at least 24 months in this nationwide population-based real-world study. Longer follow up is needed to address the long-term effectiveness.

  • 18.
    Ekström, E.
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Rosengren, V.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Kågström, S.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Forsberg, L.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Berglund, A.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Hillert, J.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, P.
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, C.
    Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Landtblom, A. -M
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Sundström, P.
    Umeå University, Clinical Science, Neurosciences, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, F.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, T.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    The long-term safety and effectiveness of natalizumab (IMSE 1) - Real-world data from a Swedish nationwide pharmaco-epidemiological study2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr Suppl. 2, s. 618-619Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. The “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (August 2006).

    Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.

    Methods: IMSE 1 includes patients starting NTZ treatment. Data is collected from the nationwide Swedish Neuroregistry. Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT) are registered prospectively.

    Results: 3476 patients (75% female; 81% RRMS) were included from August 2006 until April 2021. Mean age at treatment start was 36 years and mean treatment duration was 51.3 months. 1190 patients were currently treated with NTZ at cut-off and 13% of these were JCV positive (JCV+) with a mean JCV index at 1.07 ± 0.97. 2470 patients (71%) discontinued their NTZ treatment at some time point where the main reason was JCV+ (40%). Most of these patients switched to rituximab (39%). The number of relapses per 1,000 patient years were reduced from 380 before treatment start to 73 during treatment (25% missing data). 61% were relapse-free and 12% had only one relapse during the entire treatment period. All clinical measures showed improvement in mean between baseline and 132 months. Improvements on MSSS, MSIS-29 and SDMT were statistically significant. 117 Serious AEs had been reported to the Swedish Medical Product Agency and included nine cases (2 fatal) of progressive multifocal leukoencephalopathy (PML). Eight of these nine cases had been reported between year 2008 and 2012, and one in 2018. 17 patients died within 6 months of last NTZ infusion. The most common category for non-serious AEs was infections and infestations (21%). For serious AEs neoplasms benign, malignant and unspecified were the most common (16%).

    Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding clinical cognitive, physical and psychological measures.

  • 19.
    Ekström, E.
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Rosengren, V.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Kågström, S.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Forsberg, L.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Hillert, J.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, P.
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, C.
    Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden..
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Landtblom, A. -M
    Uppsala University, Department of Neuroscience, Uppsala, Sweden,.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden,.
    Martin, C.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden..
    Sundström, P.
    Umeå University, Clinical Science, Neurosciences, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, F.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, T.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)2021Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 27, nr Suppl. 2, s. 616-617Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Alemtuzumab (ALZ) is a modulatory drug for patients with relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long-term safety and effectiveness in a real-world setting where ALZ was included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study 3” (IMSE 3) upon launch in Sweden (March 2014).

    Objective: To follow up the effectiveness and long-term safety of ALZ in a real-world setting.

    Methods: Swedish MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg).

    IMSE 3 includes patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS). The Wilcoxon signed-rank test was used to assess changes in effectiveness.

    Results: 118 patients (59% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2021. Mean age at treatment start was 34 years. At cut-off date 85 patients had been treated with ALZ with at least 48 months of follow-up. Mean values at baseline compared to 48 months showed significant improvements for MSSS and SDMT while EQ-5D, EDSS, MSIS-29 and VAS scores showed tendencies of improvement.

    The largest proportion of the entire cohort switched from natalizumab (39%) or were treatment naïve (14%) prior ALZ. The number of relapses per 1,000 patient years decreased from 441 before ALZ initiation to 84 during ALZ treatment (16% missing data). 36 adverse events (AEs) were reported to the Swedish Medical Products Agency. 23 were classified as serious and the most common AEs categories were infections and infestations and blood and lymphatic system disorders (23% respectively). For non-serious events endocrine disorders (43%) was the most common category. Two patients died during ALZ treatment, one of which was associated to ALZ treatment, and died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.

    Conclusions: Patients treated with ALZ for at least 48 months improved or remained stable across all effectiveness measures. Continued follow-up is needed to evaluate the real-world effectiveness and safety of ALZ.

  • 20.
    Fink, K.
    et al.
    Academic Specialist Center, Centrum for Neurology, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, P.
    Lund University, Department of Neurology, Lund, Sweden.
    Alonso, L.
    Lund University, Department of Neurology, Lund, Sweden.
    Sveningsson, A.
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Lange, Niclas
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Ayad, A.
    Capio S:t Göran Hospital, Neurologiska kliniken, Stockholm, Sweden.
    Vrethem, M.
    Linköping University, Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden.
    Piehl, F.
    Academic Specialist Center, Centrum for Neurology, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    CLADCOMS - CLADribine tablets long-term Control Of MS - a post-marketing investigator driven study2022Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, nr Suppl. 3, s. 847-848, artikel-id EP1060Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Cladribine  is  a  deoxyadenosine  analogue  prodrug  that selectively  induces  immune  reconstitution  by  targeting  B-  and  T-lymphocytes. Cladribine  tablets  (CladT)  are  administered  in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation  of  long-term  safety  and  effectiveness  in  a  real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report one year follow-up data on the first 100 patients included in the study in April 2021.

    Objective: 1) To  investigate for how long a full dose treatment with Cladribine 10 mg tablets (3.5 mg/kg over two years) offers freedom of disease activity in relapsing MS patients.2) To collect complete data on safety and effectiveness with the help of the Swedish Neuroregistry to enable future assessment on effectiveness and safety in comparison with other in Sweden commonly used disease modifying treatments.

    Methods: CLADCOMS  includes  patients  with  relapsing  MS  from  the  eight academic  clinics  starting  Cladribine  treatment  after  23rd  of  March  2018. Data  is  collected  in  the  Swedish  Neuroregistry  using  highly  structured  yearly follow-up  routines.   Descriptive   data   on   relapses,   MRI   activity,   Patient   Reported   Outcome   Measures   and   Serious   Adverse   events   (SAEs)  from the  first  100  patient  included  in  the  study  are  obtained from the registry.

    Results: Up  to  April  2022  1XX  patients  were  included  in  the  study. In April 2021 the first 100 patient entered the study. 40% of patients included were treatment naïve, 29% switched from natalizumab and 13% from rituximab. By April 2022, 5 patients experienced a relapse during the treatment initiation and showed MRT activity with contrast enhancing (CEL)lesions more than six months after initiation of treatment, of which 2 patients showed CEL more than six months after the second treatment course year two. 20% of the patients showed new lesions on the first MRI performed up to 18 months after treatment initiation. Two patients reported SEAs. Analysis of CD19   and   CD27-   B-cells   counts   over   time   will   be   performed.

    Conclusions: Cladribine treatment demonstrates clinical stability in patients treated ⩾ 12 months. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine over a longer time to investigate time to disease reactivation after the second treatment course year two has been administered.

  • 21.
    Forsberg, Anette
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Familiy Medicine Research Centre, Region Örebro County, Örebro, Sweden.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Measuring postural sway in people with multiple sclerosis2015Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 4, s. 531-531Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Many people with multiple sclerosis (MS) have increased postural sway, which is associated with a higher risk of falls. Significantly increased sway has been found in people with slight or no balance impairment. Measuring postural sway is appropriate to perform in clinical settings; however, technical devices can be costly. The Swaymeter is a low-tech cheaper alter-native, considered reliable and valid in both younger and older populations (Sturnieks et al, 2011).

    Aims: To investigate the feasibility and validity of the Swaymeter in people with MS.

    Methods: Baseline values in a trial were used, with inclusion cri-teria unable to stand in tandem for 30 seconds; 87 persons with MS were tested in outpatient clinical settings, mean age 54 years (SD 11). Fifteen participants (17%) used an assistive walking device indoors and 52 (59%) outdoors. Assessments of sway were done in the bipedal stance for 30 seconds with no shoes, four con-ditions: floor eyes open (EO); floor eyes closed (EC); foam EO; and foam EC. The Swaymeter recorded displacements of the body in the horizontal plane at waist level. The displacement sway area was calculated in millimetres (anterioposterior × mediolateral). Construct validity was investigated through correlations with the Berg balance scale (BBS), the timed up and go (TUG) test, and the sit-to-stand test.

    Results: The postural sway displacements were large: floor EO (n=87) mean area 1393 mm (SD 1612); floor EC (n=82) mean area 3041 mm (SD 4447); foam EO (n=83) mean area 4007 mm (SD 3466); foam EC (n=62) mean area 9178 mm (SD 6514). For floor EO and foam EC, there was no significant correlation between the sway area and any of the balance tests. For floor with EC there was a low correlation (r=−0.266, P=0.016) between the sway area and the BBS, but not the other tests. For the condition foam with EO there were significant low–moderate correlation coefficients for the BBS (r=−0.45, P<0.001), the TUG test (r=0.26, P=0.016), and the sit-to-stand test (r=0.33, P=0.003).

    Conclusions: The Swaymeter was feasible in a clinical setting, but only 62 (71%) participants could stand on foam with EC for 30 seconds. Construct convergent validity with dynamic balance tests could not be established becausee most correlation coeffi-cients were low and non-significant. Further studies are needed to investigate the properties of the Swaymeter in MS.

  • 22.
    Forsberg, Anette
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Family Med Res Ctr, Örebro Cty Council, Örebro, Sweden.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Ctr Hlth Care Sci, Örebro Univ Hosp, Örebro, Sweden.
    Validity of a timed sit-to-stand test in people with multiple sclerosis2014Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 7, s. 992-993Artikel i tidskrift (Övrigt vetenskapligt)
  • 23.
    Forsberg, L.
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Ekström, E.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Hillert, J.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, P.
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, C.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Landtblom, A. -M
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Sundström, P.
    Umeå University, Department of Clinical Neuroscience, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, F.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, T.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Improved clinical outcomes in patients treated with natalizumab for at least 11 years - real-world data from a swedish national post-marketing surveillance study (IMSE 1)2022Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, nr Suppl. 3, s. 352-353, artikel-id P324Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).

    Objectives/Aims: To follow-up  the  long-term  effectiveness  and  safety of NTZ in a real-world setting.

    Methods: Adverse  events  (AEs),  Serious  AEs  (SAEs),  John  Cunningham  virus status  (JCV)  and  clinical  effectiveness  measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity  Scale  (MSSS),  Symbol  Digit  Modalities Test  (SDMT)  and Multiple Sclerosis Impact Scale (MSIS-29) data is collected from  the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test.

    Results: A total of 3622 NTZ patients were included in the IMSE 1 study from August 2006 until March 2022 (72% female; mean age  36  years;  80%  RRMS; mean  treatment  duration  49  months)  and  186  had  been  treated  for  at  east  132  months.  Of  the  132-month cohort, 73% were female, the mean age was 36 years, 88% had  RRMS,  and  the  mean  treatment  duration  was  155 months.  The majority were treated with interferons and glatiramer acetate prior NTZ  (64%).  25%  (47/186)  discontinued  NTZ  treatment  of  which 47% (n=22) discontinued due to JCV positive (JCV+). In total,  30%  (55/186)  of  these patients  were  JCV+  with  a  mean  JCV index of 1.2±1.0 (2% missing data). Relapses before treatment were reduced from 380/1000 patient years to 43/1000 during treatment,  71%  were  relapse-free  and  18%  had  1  relapse  during  the entire  treatment  period  (15%  missing  data).  Most  clinical  effectiveness measures, MSSS, MSIS-29 and SDMT showed statistically  significant  improvement between  baseline  and  132  months (p<0.05). Over the entire observation time, 125 SAEs had been reported to the Swedish MPA including 9 cases (2 fatal) of progressive  multifocal  leukoencephalopathy  (PML)  of  which  8  occurred between 2008 and 2012, and one in 2018.

    Conclusions: NTZ  is  generally  well  tolerated  with  sustained  effectiveness regarding  cognitive,  physical  and  psychological  measures, as well as relapse-control. Introduction of JCV testing has  led  to  fewer  treated  JCV+  patients, which  likely  explains  a  drastic drop in number of reported cases of PML.

  • 24.
    Forsberg, L.
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Ekström, E.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Hillert, J.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, P.
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, C.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden.
    Lycke, J.
    University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Lantblom, A. -M
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Department of Clinical Sciences, Stockholm, Sweden,.
    Sundström, P.
    Umeå University, Department of Clinical Neuroscience, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, F.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, T.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Clinical effectiveness and safety of dimethyl fumarate for patients treated at least 6 years in the swedish post-market surveillance study "immunomodulation and multiple sclerosis epidemiology 5" (IMSE 5)2022Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, nr Suppl. 3, s. 858-859, artikel-id EP1078Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

    Objectives/Aims: To assess the effectiveness and safety of DMF with focus on patients treated at least 72 months.

    Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS), Adverse Events (AEs) and Serious AEs (SAEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: 2565 DMF-treated patients were included between March 2014 and March 2022 with an overall drug survival rate of 38.7% and a mean treatment duration of 37 months. The main reasons for discontinuation were AEs (47%) and lack of effect (30%). 199 AEs were reported of which 63 were serious. For both serious and non-serious AEs reported, gastrointestinal disorders were the most common (19% and 27%, respectively).509 patients had continuous treatment for at least 72 months. This cohort had a mean age of 42 years and a mean treatment duration of 84 months. The majority (51%) had switched from interferon or glatiramer acetate and 24% were treatment naïve.Significant improvements in mean values at 72 months of treatment compared to baseline were noted for MSSS, MSIS-29 Psychological, and EQ-5D (p<0.05). All other tests remained stable after 6 years of treatment. Number of relapses per 1000 patient years were improved from 199.6 before DMF treatment start to 23.0 during treatment with DMF.49 patients (10%) have discontinued DMF treatment in the 72 month cohort with a mean treatment duration of 84 months (range 70-97 months). The main reasons for discontinuation were other reasons (33%), lack of effect (29%), stable condition (14%), and AEs (12%).

    Conclusions: DMF demonstrates partly clinical improvements in patients treated 72 months. However; due to the high discontinuation rate there is an unavoidable selection bias. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.

  • 25.
    Forsberg, L.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Clinical effectiveness of dimethyl fumarate with focus on patients treated at least 36 months - a Swedish nationwide study of the long-term effectiveness and safety of dimethyl fumarate (IMSE5)2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 316-317Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

    Objective: To assess the effectiveness and safety of DMF with focus on patients treated at least 36 months in the IMSE study.

    Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: 2229 DMF-treated patients were included since March 2014 with a one- and two-year drug survival rate of 73% and 59%. The main reasons for discontinuation were AEs (51%) and lack of effect (29%). 77 AEs were reported to the Swedish Medical Products Agency of which 20 were serious. There were 6 fatal cases of which 4 were confirmed as unrelated to DMF and 2 were still under investigation.865 patients had continuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 44 months. The majority had switched from interferon and glatiramer acetate (IFN&GA) (50%) or were treatment naïve (TN) (22%). Significant improvements in mean values at 36 months of treatment compared to baseline were noted for EDSS, MSSS, SDMT, MSIS-29 Psychological and EQ-5D. When TN patients were solely assessed improvements were noted for EDSS, MSSS, SDMT, MSIS-29 Physical and Psychological and EQ-5D. Treatment experienced patients displayed significant improvements only for MSSS and EQ-5D. Patients previously treated with IFN&GA also improved only in MSSS and EQ-5D. TN patients had a mean duration from diagnosis to treatment start of 6 months compared to 83 months for IFN&GA patients and 105 months for the remaining cohort.

    Conclusions: DMF demonstrates clinical improvements in patients treated ⩾ 36 months, most pronounced in TN patients. However; the tolerability of DMF was reduced since 41% interrupted treatment during the first 24 months of therapy. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.

  • 26.
    Forsberg, L.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish Nationwide study of the long-term effectiveness and safety of teriflunomid based on data from the Swedish "Immunomodulation and Multiple Sclerosis Epidemiology" Study (IMSE 4)2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 316-316Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Teriflunomid (TFM) is a newly approved oral therapy for relapsing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE) in order to track the long-term safety and effectiveness in a real-world setting.

    Objectives: To track the long-term safety and effectiveness of TFM in a real-world setting.

    Methods: A large majority of MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Drug survival was measured using the Kaplan-Meier curve.

    Results: A total of 559 TFM-treated patients had been included in the IMSE 4 study from March 2014 to March 2019. 71 % were female and the mean age at treatment start was 46 years. The mean treatment duration was 23 months and 89 % of the patients had RRMS (9 % missing data on MS phenotype). Most patients switched from interferon/glatiramer acetate (36 %) and 16 % of the patients were treatment naïve before starting TFM. The overall one-year drug survival rate was 74 % and the overall two-year drug survival rate was 58 %. 232 (42 %) patients had terminated their treatment at some point, of which 46 % started rituximab treatment and 12 % had no new treatment registered. The most common reasons for discontinuation were AEs (41 %) and lack of effect (39 %). 229 patients had been continuously treated with TFM for ⩾24 months and significant changes in mean baseline values compared to values at 24 months were noted for EDSS (1.9 ± 1.5 to 2.1 ± 1.6, n=66) and SDMT (50.3 ± 10.5 to 52.3 ± 13.0, n=88). A total of 34 AEs were reported to the Swedish Medical Products Agency of which 9 events were classified as serious, none fatal.

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. Patients starting TMF are older at treat-ment start than most other DMTs, which may explain the lack of improvement in EDSS scores. Still, a relatively high proportion switched due to lack of effect. A longer follow-up period is needed to assess the real-world effectiveness and safety of TMF.

  • 27.
    Forsberg, L.
    et al.
    Karolinska Institutet, Solna, Sweden.
    Kågström, S.
    Karolinska Institutet, Solna, Sweden.
    Leandersson, Å.
    Karolinska Institutet, Solna, Sweden.
    Berglund, A.
    Karolinska Institutet, Solna, Sweden.
    Hillert, J.
    Karolinska Institutet, Solna, Sweden.
    Nilsson, P.
    Lund University, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Institute of Neuroscience and Physiology, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Sundström, P.
    Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Institutet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Stockholm, Sweden.
    A swedish post-market surveillance study: long-term effectiveness and safety of dimethyl fumarate (imse 5) for patients treated at least 36 months: on-demand eposters p0001-p02862020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 254-255Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Dimethyl fumarate (DMF) is an oral therapy for relapsing-remitting multiple sclerosis (RRMS). DMF is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

    Objectives: To assess the effectiveness and safety of DMF with focus on patients treated at least 36 months in the IMSE study.

    Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: 2349 DMF-treated patients were included between March 2014 and June 2020 with an overall drug survival rate of 45%. The main reasons for discontinuation were AEs (50%) and lack of effect (30%). 186 AEs were reported to the Swedish Medical Products Agency, of which 59 were serious. A total of 8 patients have died during DMF treatment or within 6 months of treatment discontinuation. 36 month cohort: 940 patients had con-tinuous treatment for at least 36 months. This cohort had a mean age of 42 years and a mean treatment duration of 56 months. The majority (50%) had switched from interferon or glatiramer ace-tate, and (24%) were treatment naïve (TN). Significant improve-ments in mean values at 36 months of treatment compared to baseline for the 36-month cohort were noted for MSSS, SDMT, MSIS-29 Psychological, EQ-5D and VAS. When TN patients were solely assessed (n=230) improvements were noted for all above mentioned measures as well as MSIS-29 Psychological. The remaining patients in the cohort; treatment experienced patients (n=710) displayed significant improvements only for MSSS, MSIS-29 Psychological and EQ-5D. TN patients had a mean duration from diagnosis to treatment start of 5 months com-pared to 91 months for the remaining cohort. TN were also younger than the remaining cohort (37 years vs 43 years).Conclusions: DMF demonstrates clinical improvements in patients treated 36 months, more pronounced in TN patients. However; due to the high discontinuation rate there is an unavoidable selection bias. Continued follow up is needed to assess the effectiveness and safety of DMF over longer time periods in a real world setting.

  • 28.
    Forsberg, L.
    et al.
    Karolinska Instituet, Solna, Sweden.
    Kågström, S.
    Karolinska Instituet, Solna, Sweden.
    Leandersson, Å.
    Karolinska Instituet, Solna, Sweden.
    Hillert, J.
    Karolinska Instituet, Solna, Sweden.
    Nilsson, P.
    Lund University, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Institute of Neuroscience and Physiology, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Instituet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Stockholm, Sweden.
    A swedish post-market surveillance study of the long-term effectiveness and safety of teriflunomid (IMSE 4) for patients treated at least 36 months2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 253-254Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Teriflunomid (TFM) is an oral therapy for relaps-ing-remitting multiple sclerosis (RRMS), which has been included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

    Objectives: To assess the long-term safety and effectiveness of TFM for patients treated in a real-world setting over time.

    Methods: A large majority of MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). The IMSE 4 study obtains descriptive data of adverse events (AEs), Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - Five Dimensions Test (EQ-5D) and Visual Analog Scale (VAS) from NeuroReg. Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: 609 TFM-treated patients had been included in the IMSE 4 study from March 2014 to June 2020, 70% were female and mean age at treatment start was 46 years. Mean treatment duration was 27 months and 89% of the patients had RRMS. The most common prior treatment was interferon beta or glatiramer acetate (39%) and 17% of the patients were treatment naïve. The overall one- two- and three- year drug survival rates were 73%, 59% and 48% respectively. 307 (50%) patients had discontinued treatment at some point, of which 34% started rituximab treatment (36% had no new treatment registered). The most common rea-sons for discontinuation were AEs (42%) and lack of effect (40%). 204 patients had been continuously treated with TFM for ⩾36 months and significant changes in mean baseline values compared to values at 36 months were noted only for EDSS (2.0 ± 1.6 to 2.3 ± 1.8, n=49). All other clinical measures were stable. A total of 68 AEs were reported of which 20 events were classified as serious (S). The most common AE category was skin and subcutaneous tissue disorders for both serious and non-serious (NS) AEs (S: 25%, NS: 21%).

    Conclusions: NeuroReg proves to function well as a post-market-ing drug surveillance platform, providing data regarding drug effectiveness and AEs. Patients starting TMF are older at treat-ment start than patients initiating most other DMTs, which may explain the lack of significant improvement in most clinical meas-ures and the negative outcome of the EDSS scores. A longer fol-low-up period is needed to assess the real-world effectiveness and safety of TMF.

  • 29.
    Forsberg, L.
    et al.
    Karolinska Institutet, Solna, Sweden.
    Kågström, S.
    Karolinska Institutet, Solna, Sweden.
    Leandersson, Å.
    Karolinska Institutet, Solna, Sweden.
    Hillert, J.
    Karolinska Institutet, Solna, Sweden.
    Nilsson, P.
    Lund Univiversity, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Danderyd, Sweden.
    Lycke, J.
    Institute of Neuroscience and Physiology, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Sundström, P.
    Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Institutet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Stockholm, Sweden.
    A swedish post-market surveillance study: long-term effectiveness and safety of cladribine tablets (IMSE 10) for patients treated at least 12 months2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 254-254Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Cladribine is a deoxyadenosine analogue prodrug. Cladribine tablets (CT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). CT are included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology” (IMSE).

    Objectives: To assess the safety and effectiveness of CT in a real-world setting with focus on patients treated at least 12 months.

    Methods: Descriptive data of Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS), relapses and Adverse Events (AEs) is obtained from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and relapse rates were tested using the paired samples T-test.

    Results: 85 patients were included in the IMSE 10 study since CT were introduced on the Swedish market in April 2018. 42 patients were treated for at least 12 months. Five AEs were reported since the study start, four were classified as infections and infestations. 25 % of the entire cohort was treated with CT as their first MS drug. 13 % were treated with natalizumab and 12 % with dimethyl fumarate prior to CT. Five AEs were reported since the study start, four were classified as infections and infestations. Relapse data was available for 27/42 patients in the 12-month cohort. The number of reported relapses decreased significantly from 208.6 per 1,000 patient years before treatment start to 83.6 during treatment. Only three patients in this cohort experienced a relapse during treatment of which two were during the first treatment year. Significant improvements in mean values at 12 months of treatment compared to baseline were noted for MSSS for the 12-month cohort (n=17). All other tests remained stable but significantly unchanged after one year of treat-ment. Lymphocyte levels decreased from a mean of 2.4 x 109/L at treatment start (n=8) to 1.2 x 109/L after 12 months of treatment (n=6) in the 12-month cohort. No patients were below the 0.8 x 109/L limit at 12 months.

    Conclusions: CT treatment demonstrates clinical stability in patients treated 12 months. However, continued follow-up is needed to assess the effectiveness and safety of CT over a longer time to assess if these results sustain after the final treatment course has been administered.

  • 30.
    Forsberg, Linda
    et al.
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Larsson, Veronica
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Hillert, Jan
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Nilsson, Petra
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Svenningsson, Anders
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Lycke, Jan
    University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    Burman, Joachim
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    Martin, Claes
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Sundström, Peter
    Umeå University, Department of Science, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, Fredrik
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Olsson, Tomas
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    A comparison of administration and discontinuation of Natalizuamb in Sweden over time for patients treated with either sucutaneous (SC) or intravenous (IV) administration methods since July 20212023Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 29, nr Suppl. 3, s. 617-617, artikel-id P716/2335Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing multiple sclerosis (RMS) originally launched as an intravenous (IV) therapy in Sweden in August 2006. A new subcutaneous (SC) administration method for NTZ was launched in April 2021.

    Objectives/Aims: To investigate how the administration of NTZ has evolved in Sweden since the introduction of SC NTZ in 2021, and to explore potential differences in treatment discontinuation patterns between the SC or IV administration modalities.

    Methods: Descriptive data will be presented from the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) study cohort. Data is collected from the nationwide Swedish Neuro Registry (NeuroReg). The drug survival is assessed using the Kaplan Meier one-year drug survival curve and Breslow Wilcoxon test of equality distribution.

    Results: A total of 4011 NTZ participants were included in the IMSE 1 study from August 2006 until March 2023 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 49 months), including 295 since July 2021, of which 264 had available data on method of administration. In this cohort, 109 (41%) initiated IV NTZ, of which 16 (15%) later switched to SC administration, and 155 (59%) initiated treatment with SC NTZ. The distribution between administration methods altered over time, where IV was more common in Q3 2021 (70%) and then successively dropped to 31% in Q1 2023.The mean age at treatment start was 36 years (35 for IV and 37 for SC) and 69% (70% IV, 68% SC) were female.Out of 264 participants, 73 (28%) later discontinued treatment. Discontinuation was numerically more common in the IV group compared with the SC group, but differences in the one-year drug survival rate did not reach statistical significance.The most common reason for discontinuation in the IV group was “other reason; unspecified” followed by positive JC-virus serology (JCV+). In the SC group JCV+ was the most common reason for discontinuation. Four patients discontinued due to neutralizing NTZ antibodies; 2 in each group.

    Conclusion: The SC administration has become the preferred administration method for NTZ since its launch in the spring of 2021, with 59% of NTZ treatment initiations being administered using SC method. We did not find significant differences in discontinuation rates between the two administration methods. Longer observation periods will be needed to assess possible differences in tolerability and treatment adherence between the two administration modalities.

  • 31.
    Forsberg, Linda
    et al.
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Larsson, Veronica
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Hillert, Jan
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Nilsson, Petra
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Svenningsson, Anders
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Lycke, Jan
    University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala University, Department of Neuroscience, Uppsala, Sweden.
    Burman, Joachim
    Uppsala University, Department of Medical Science, Uppsala, Sweden.
    Martin, Claes
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Sundström, Peter
    Umeå University, Department of Science, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, Fredrik
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Olsson, Tomas
    Karolinska Institutet, Department of Neuroscience, Solna, Sweden.
    Improved clinical outcomes in patients treated with Natalizumab for at least 11 years - Real-world data from a Swedish national post-marketing surveillance study (IMSE 1)2023Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 29, nr Suppl. 3, s. 965-966, artikel-id P1512/2294Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing multiple sclerosis (RMS). Post-marketing surveillance is important to evaluate the long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon launch of NTZ in Sweden (Aug 2006).

    Objectives/Aims: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.

    Methods: Adverse events (AEs), Serious AEs (SAEs), John Cunningham virus status (JCV) and clinical effectiveness measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Impact Scale (MSIS-29) data were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures were assessed using the Wilcoxon Signed Rank Test.

    Results: A total of 4011 NTZ patients were included in the IMSE 1 study from August 2006 until March 2023 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 52 months) and 249 had been treated for at least 132 months. Of the 132-month cohort, 75% were female, the mean age was 36 years, 88% had RRMS, and the mean treatment duration was 160 months. The majority were treated with interferons and glatiramer acetate prior to NTZ (68%), where 30% (74/249) discontinued NTZ treatment; 43% (32/74) due to being JCV positive (JCV+), with a mean JCV index of 1.1±0.9 (n=66). Annualized relapse rates dropped from 0.40 in the year before treatment start to 0.04 during treatment, where 68% were entirely free of relapses and 21% had only 1 relapse during the entire treatment period (17% missing data). All clinical effectiveness measures, except EDSS showed statistically significant improvement between baseline and 132 months (p<0.05).From the entire IMSE1 cohort (N=4011), 132 SAEs have been reported to the Swedish MPA, including 9 cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which 8 occurred between 2008 and 2012, and one in 2018.

    Conclusion: NTZ is generally well tolerated and displays sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control. Introduction of JCV testing has led to fewer treated JCV+ patients, likely explaining a drastically reduced incidence of PML.

  • 32.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbuker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3)2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 706-707Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Alemtuzumab (ALZ) is a modulatory drug for patients with relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study 3” (IMSE 3) upon launch in Sweden (March 2014).

    Objective: To follow up the effectiveness and long-term safety of ALZ in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes patients starting ALZ treatment. Adverse events (AEs) and clinical meas-ures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS) are obtained from NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness.

    Results: 110 patients (60% female; 95% RRMS) have been included in IMSE 3 between March 2014 and April 2018. Mean age at treatment start was 34 years and mean treatment duration was 28 months. Most patients (40%) switched from natalizumab and 14% were treatment naïve. 103 patients were currently treated with ALZ at cut-off date and 97 patients had been treated for at least 12 months. Seven patients had discontinued ALZ treatment, of which five patients switched to another disease modifying therapy, one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis and one patient had no treatment registered after ALZ discontinuation. In total, 20 AEs were reported to the Swedish Medical Products Agency; 13 events were classified as non-serious. In patients treated at least 12 months significant improvements were seen for EDSS (2.0±1.4 to 1.6±1.3, n=67), MSSS (3.4±2.6 to 2.6±2.3, n=58), MSIS-29 Physical (22.9±21.0 to 17.5±18.0, n=83), VAS (66.9±22.0 to 73.7±18.5, n=68) and EQ-5D (0.7±0.3 to 0.8±0.3, n=74). MSIS-29 Psychological and SDMT did not improve significantly.

    Conclusions: NeuroReg functions well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. A longer follow-up period is needed to evaluate the real-world effectiveness and safety of ALZ.

  • 33.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbüker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of fingolimod (IMSE 2)2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 696-697Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Fingolimod (FGL) is an oral therapy for patients with relapsing-remitting multiple sclerosis (RRMS) and the efficacy has been shown in phase II and III studies. However; long-term surveillance and safety is important, therefore FGL is included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study 2” (IMSE 2).

    Objective: To follow up the effectiveness and long-term safety of FGL in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes data of adverse events (AEs) and clinical measures; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS), obtained from NeuroReg.

    Results: From September 2011 until April 2018, 1617 patients (67% female; 91% RRMS) were included in IMSE 2. At treatment start 38 patients were ≤20 years (yr), 308 aged 21-30 yr and 1271 aged >30 yr. Mean treatment duration was 34 months. 852 patients were currently treated with FGL at cut-off date and 1230 patients had been treated for at least 12 months. In total, 39% switched treatment from interferons or glatiramer acetate, 26% from natalizumab and 5% from dimethyl fumarate or teriflunomide. 803 patients have discontinued FGL at some point, mainly due to lack of effect (43%) or AEs (34%), most patients switched to rituximab after FGL discontinuation. Relapses were reduced from 281 to 87/1000 patient years (PY) when comparing before and during FGL treatment. In patients aged ≤20 yr, 21-30 yr and >30 yr relapses were reduced from 694 to 144/1000 PY, 455 to 129/1000 PY and 258 to 77/1000 PY, respectively. After 12 months significant improvements were seen in EQ-5D (0.7 to 0.8, n=752), MSSS (3.1 to 2.9, n=410), MSIS-29 Physical (21.1 to 20.0 n=812), MSIS-29 Psychological (29.2 to 24.9, n=812), SDMT (54.3 to 57.0, n=751) and VAS (70.9 to 72.8, n=692). When analysing age groups separately significant improvements were seen in MSSS, SDMT, and MSIS-29 Psychological in patients aged 21-30 yr and >30 yr. EQ-5D, VAS and MSIS-29 Physical significantly improved in patients aged >30 yr.

    Conclusions: FGL is a generally well-tolerated drug that reduces the clinical activity in MS patients. NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and AEs.

  • 34.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Forsberg, L.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (IMSE 3) for patients treated at least 24 months2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 327-328Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Alemtuzumab (ALZ) is an approved disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) upon launch in Sweden (March 2014).

    Objective: To track effectiveness and long-term safety of ALZ in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 3 includes all patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS).

    Results: A total of 118 MS patients (59% female; 95% RRMS) were included in IMSE 3 between March 2014 and April 2019. 95 patients had started ALZ >24 months ago (63% female; 98% RRMS) at cut-off date (31st of Mars 2019), where only 3 patients had switched to another DMT. Mean age at treatment start for patients treated at least 24 months was 34 years and mean treatment duration was 42 months. Mean number of drugs prior ALZ initiation was 2.3. Most patients (41/95) switched to ALZ from natalizumab, while 14/95 patients were treatment naïve with ALZ. The number of relapses per 1,000 patient years decreased from 471 before ALZ initiation to 65 during ALZ treatment (n=83, missing data; n=12). In patients treated ⩾ 24 months significant improvements in mean were seen for EDSS (1.9 ± 1.4 to 1.6 ± 1.3, n=57), MSSS (3.3 ± 2.6 to 2.4 ± 2.1, n=48) and EQ-5D (0.7 ± 0.3 to 0.8 ± 0.3, n=53), while MSIS-29, SDMT and VAS scores remained stable. A total of 28 adverse events were reported to the Swedish Medical Products Agency, 12 events were classified as serious and 16 events as non-serious. Two patients died during ALZ treatment, of which one patient died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.

    Conclusions: Patients treated with ALZ for at least 24 months improved or remained stable across all effectiveness measures. Only a very small percentage of patients switched to other DMTs. Continued follow-up is needed to address long term effectiveness and safety of ALZ.

  • 35.
    Fält, A.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kågström, S.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Forsberg, L.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd, Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd, Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish real word study of the long-term effectiveness and safety of fingolimod (IMSE 2) with focus on patients treated at least 48 months2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 536-537Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis (RRMS) introduced in Sweden 2011. Already from launch FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort.

    Objective: To track the effectiveness and long-term safety of FGL in a real-world setting.

    Methods: Swedish MS patients are registered into the nationwide Swedish Neuro Registry (NeuroReg). IMSE 2 includes patients starting FGL treatment and clinical and demographic data are collected from the NeuroReg. The Wilcoxon signed-rank test was used to assess changes in effectiveness measures.

    Results: From September 2011 until April 2019, 1652 MS patients (67% female; 90% RRMS) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 39 months. 608 patients (64% female; 91% RRMS) had been treated with FGL for at least 48 months with a mean age at treatment start of 40 years and a mean treatment duration of 70 months. A majority (330/608) switched to FGL from interferons/glatiramer acetate, while 194/608 switched from natalizumab. 105/608 patients had discontinued FGL at some point, mainly due to lack of effect (31%) and adverse events (31%). Most patients (57/105) switched to rituximab after FGL discontinuation. The number of relapses per 1,000 patient years were reduced from 275 before FGL initiation to 40 during FGL treatment (27% missing data). In patients treated with FGL at least 48 months significant changes (mean) were seen in Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT) and Visual Analogue Scale (VAS). 80/184 patients had a 4-point or 10% increase in SDMT score between baseline and 48 months. In total 167 adverse events were reported to the Swedish Medical Products Agency of which 77 events were classified as serious.

    Conclusions: FGL displays a relatively high degree of drug persistence and clinical effectiveness is retained over time with significant improvements in MSSS, SDMT and VAS in patients treated at least 48 months. Furthermore, NeuroReg functions well as a drug surveillance platform, enabling monitoring of long-term effectiveness and safety.

  • 36.
    Granqvist, Mathias
    et al.
    Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
    Burman, Joachim
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lycke, Jan
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Nilsson, Petra
    Neurology Clinic, Skåne University Hospital, Lund, Sweden.
    Olsson, Tomas
    Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
    Sundström, Peter
    Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Svenningsson, Anders
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Vrethem, Magnus
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Frisell, Thomas
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Piehl, Fredrik
    Department of Clinical Neuroscience, Center for Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
    Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 12, s. 1532-1539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Population-based real-world evidence studies of the effectiveness and tolerability of dimethyl fumarate in relation to common treatment alternatives are still limited.

    OBJECTIVE: To evaluate the clinical effectiveness and tolerability of dimethyl fumarate (DMF) as the initial and secondary treatment for relapsing-remitting multiple sclerosis (RRMS) patients compared with common treatment alternatives in Sweden.

    METHODS:  We conducted a nationwide retrospective observational cohort study of all RRMS patients identified through the Swedish MS registry initiating DMF (n = 641) or interferons/glatiramer acetate (IFN/GA; n = 555) as the initial therapy, or DMF (n = 703) or fingolimod (FGL; n = 194) after switch from IFN/GA between 1 January 2014 and 31 December 2016.

    RESULTS: The discontinuation rate was lower with DMF as the initial treatment than IFN/GA (adjusted hazard rate (HR): 0.46, 95% confidence interval (CI): 0.37-0.58, p < 0.001), but higher than FGL as the secondary treatment (HR: 1.51, CI: 1.08-2.09, p < 0.05). Annualized relapse rate (ARR) was lower with DMF compared to IFN/GA (0.04, CI: 0.03-0.06 vs 0.10, CI: 0.07-0.13; p < 0.05), but not FGL (0.03, CI: 0.02-0.05 vs 0.02, CI: 0.01-0.04; p = 0.41). Finally, time to first relapse (TTFR) was longer with DMF as the initial, but not secondary, therapy (p < 0.05 and p = 0.20, respectively).

    CONCLUSION: Our findings indicate that DMF performs better than IFN/GA as the initial treatment for RRMS. Compared to FGL, DMF displayed a lower tolerability, but largely similar effectiveness outcomes.

  • 37.
    Gunn, H.
    et al.
    University of Plymouth, Plymouth, England.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Cameron, M.
    Oregon Health & Science University, Portland OR, USA.
    Hoang, P.
    Neuroscience Research Australia, Randwick NSW, Australia.
    Mazumder, R.
    Oregon Health & Science University, Portland OR, USA.
    Freeman, J.
    University of Plymouth, Plymouth, England.
    Lord, S.
    Neuroscience Research Australia, Randwick NSW, Australia.
    Falls in people with multiple sclerosis: an international perspective2013Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 11, s. 45-45Artikel i tidskrift (Övrigt vetenskapligt)
  • 38.
    Hillert, J.
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Bove, R.
    University of California, San Francisco, United States.
    Haddad, L. B.
    Population Council, Center for Biomedical Research, New York, United States.
    Hellwig, K.
    Katholisches Klinikum Bochum gGmbH, Nordrhein-Westfalen, Germany.
    Houtchens, M.
    Harvard Medical School and Brigham and Women’s Hospital, Boston, United States.
    Magyari, M.
    Danish Multiple Sclerosis Center, Copenhagen, Denmark.
    Merki-Feld, G. S.
    Clinic of Reproductive Endocrinology, University Hospital Zürich, Zürich, Switzerland.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Nappi, R. E.
    Research Center of Reproductive Medicine, IRCCS San Matteo Foundation, Pavia, Italy; University of Pavia, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Pavia, Italy.
    Stenager, E.
    University of Southern Denmark, Department of Regional Research, Odense, Denmark; MS-clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding), Jutland, Denmark.
    Thompson, H.
    Southern Health & Social Care Trust, Portadown, United Kingdom.
    Tulek, Z.
    Istanbul University-Cerrahpaşa, Florence Nightingale Faculty of Nursing, Istanbul, Turkey.
    Di Cantogno, E. Verdun
    EMD Serono Research & Development Institute (an affiliate of Merck KGaA), Billerica, United States.
    Simoni, M.
    University of Modena and Reggio Emilia, Unit of Endocrinology, Department of Medical Specialties, University Hospital and Department of Biomedical, Metabolic and Neural Sciences, Modena, Italy.
    Expert opinion on the use of contraception in people with multiple sclerosis2022Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, nr Suppl. 3, s. 187-188, artikel-id P080Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: The most appropriate use, type, and timing of contraception in people with multiple sclerosis (PwMS) is poorly understood, and specific guidance is absent.

    Aims  and  Objectives: To  provide  insight  into  potential  clinical  guidelines for the use of contraception by PwMS through development  of  recommendations  by a  consensus-based  program  led  by international clinical experts.

    Methods:  A  multidisciplinary  steering  committee  (SC)  of  13  international expert healthcare professionals (HCPs) identified 15 key clinical questions on the use of contraception in PwMS, which addressed issues relating to patient-centred care, selection of contraception for PwMS, and time needed to use contraception since the last dose of disease modifying therapies (DMTs). Twenty-five clinical recommendations  addressing  the  questions  were  drafted  using evidence obtained from a comprehensive systematic literature  review  combined  with expert  opinion  from  the  SC.  An  extended faculty of 32 HCPs from 18 countries including a patient association representative, and the SC members (n=12), voted on the   recommendations.   Consensus   on   recommendations   was   achieved when  ⩾75%  of  respondents  expressed  an  agreement  score of 7–9, on a 9-point scale.

    Results: Overall, consensus was achieved on 24 out of 25 clinical recommendations. In detail, consensus in the range of 90–100% was  achieved on 11  recommendations,  12  recommendations  achieved  80–89%  consensus,  and 1  recommendation  achieved  75–79%  consensus  (n=44).  The  strength  of recommendations  ranged from 7–9. The one statement failing to achieve consensus scored 74.1%. Clinical recommendations are provided on the process of prescribing contraception for PwMS, including the recommended types of HCPs involved and optimal topics to discuss; the range of contraceptive options and the key considerations involved in selecting an appropriate method of contraception; and the timing of starting and stopping contraception in relation to the use of DMTs.

    Conclusions: These  expert  recommendations  were  based  on  a  robust consensus approach, providing timely and practical guidance on the use of contraception for HCPs treating PwMS and will form the basis of further publications and clinical tools.

  • 39.
    Hillert, Jan
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Bove, Riley
    UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
    Haddad, Lisa B.
    Center for Biomedical Research, Population Council, New York, NY, USA.
    Hellwig, Kerstin
    Katholisches Klinikum Bochum GmbH, Nordrhein-Westfalen, Bochum, Germany.
    Houtchens, Maria
    Brigham and Women's Hospital, Boston, MA, USA/ Harvard Medical School, Boston, MA, USA.
    Magyari, Melinda
    Danish Multiple Sclerosis Center, University Hospital Boston, MA, USA/ Rigshospitalet, Copenhagen, Denmark.
    Merki-Feld, Gabriele S.
    Clinic of Reproductive Endocrinology, University Hospital Zürich, Zürich, Switzerland.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nappi, Rossella E.
    Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy; Research Center of Reproductive Medicine, IRCCS San Matteo Foundation, Pavia, Italy.
    Stenager, Egon
    Department of Regional Research, University of Southern Denmark, Odense, Denmark; MS-Clinic of Southern Jutland (Aabenraa, Esbjerg, Kolding), Sønderborg, Denmark.
    Thompson, Heidi
    Southern Health & Social Care Trust, Portadown, Northern Ireland.
    Tulek, Zeliha
    Istanbul University-Cerrahpasa, Florence Nightingale Faculty of Nursing, Istanbul University-Cerrahpasa, Istanbul, Turkey.
    Verdun Di Cantogno, Elisabetta
    EMD Serono Research & Development Institute, Inc., Billerica, MA, USA.
    Simoni, Manuela
    Unit of Endocrinology, Department of Medical Specialties, University Hospital and Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
    Expert opinion on the use of contraception in people with multiple sclerosis2024Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, artikel-id 13524585241228103Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    BACKGROUND: Current guidance on the selection of appropriate contraception for people with multiple sclerosis (PwMS) is lacking.

    OBJECTIVE: To address this gap, an expert-led consensus program developed recommendations to support clinicians in discussing family planning and contraception with women and men with multiple sclerosis (MS).

    METHODS: A multidisciplinary steering committee (SC) of 13 international clinical experts led the program, supported by an extended faculty of 32 experts representing 18 countries. A modified Delphi methodology was used for decision-making and consensus-building. The SC drafted 15 clinical questions focused on patient-centered care, selection of contraception, and timing of stopping/starting contraception and disease-modifying therapies (DMTs). Statements addressing each question were drafted based on evaluation of published evidence and the experts' clinical experience. Consensus was reached if ⩾75% of respondents agreed (scoring 7-9 on a 9-point scale) with each recommendation.

    RESULTS: Consensus was reached on 24 of 25 proposed recommendations, including how and when to discuss contraception, types and safety of contraceptives, and how to evaluate the most appropriate contraceptive options for specific patient groups, including those with significant disability or being treated with DMTs.

    CONCLUSION: These expert recommendations provide the first practical, relevant, and comprehensive guidance for clinicians on the selection of contraception in PwMS.

  • 40.
    Jons, D.
    et al.
    University of Gothenburg, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Göteborg, Sweden.
    Bergström, T.
    University of Gothenburg, Clinical Microbiology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Zetterberg, H.
    University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Dahlgren’s Academy, Göteborg, Sweden.
    Biström, M.
    Umeå University, Department of Clinical Science, Neurosciences, Umeå, Sweden.
    Alonso-Magdalena, L.
    Skåne University Hospital, Department of Neurology, Lund, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Vrethem, M.
    Linköping University, Department of Neurology and Department of Clinical and Experimental Medicine, Linköping, Sweden.
    Blennow, K.
    University of Gothenburg, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Dahlgren’s Academy, Göteborg, Sweden.
    Nilsson, S.
    University of Gothenburg, Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, Göteborg, Sweden.
    Huang, J.
    Karolinska Institute, Neuroimmunology Unit, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Stockholm, Sweden.
    Kockum, I.
    Karolinska Institute, Neuroimmunology Unit, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, T.
    Karolinska Institute, Neuroimmunology Unit, The Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Stockholm, Sweden.
    Waterboer, T.
    German Cancer Research Center (DKFZ), Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, Heidelberg, Germany.
    Sundström, P.
    Umeå University, Department of Clinical Science, Neurosciences, Umeå, Sweden.
    Andersen, O.
    University of Gothenburg, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Göteborg, Sweden.
    Increase in Epstein Barr virus serologies precedes neuroaxonal damage in pre-symptomatic multiple sclerosis2022Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 28, nr Suppl. 3, s. 86-87, artikel-id O111Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Epstein-Barr virus (EBV) infection may be a pre-condition  for  the development  of  multiple  sclerosis  (MS).  EBV  antibodies, predominantly anti-EBNA1, develop in the presymp-tomatic phase of virtually all MS patients. Using material from a serum repository, studies in advance of MS onset indicated that EBV  seropositivity  preceded  the  first  expression  of  incipient  axonal lesions, serum Neurofilament Light (sNFL) .

    Objectives: To  determine  the  onset  and  individual  order  of  appearance  of EBV  seroreactivity  and  the  serum  neuroaxonal  injury marker neurofilament light (sNfL) in a wide age spectrum of presymptomatic MS patients.

    Aims: To  characterize  the  presymptomatic  appearance  of  anti-bodies against an intranuclear (EBNA1) and a surface EBV anti-gen (gp350) and sNfL.Methods:  A nested  case-control  study  in  669  pre-symptomati-cally acquired blood samples from persons who later received an MS diagnosis, and from 1:1 matched control persons. Serum lev-els of EBNA1, VCA and gp350 IgG antibodies and sNFL (n=519) were   measured   in   individual   presymptomatic   samples   and   expressed  as delta  scores  with  matched  controls  in  relation  to  time until MS onset.

    Results: Serum levels expressed as delta scores for anti EBV and NfL IgG showed an incipient increase for anti EBNA1 and gp350 from  15-20  years  before  MS debut.  Significant  (p=0.001  and  p=0.002) from 10-15 years, with consistent delta-scores succes-sively closer to MS onset. These findings contrasted to the level of sNfL which increasingly diverged from matched controls from 5-10 years before the onset of MS. None of the individual sam-ples  negative  for  both EBNA1 and  VCA  IgG  antibodies  in  the  pre-MS group (n = 36) showed any elevation of the sNfL level.

    Conclusions: In  a  pre-MS  material,  the  seroreactivity  against  EBNA1  was followed  by  VCA  and  gp350,  before  increased  sNFL appeared, indicating incipient axonal injury. Together with its biological characteristics this temporal order confirms the role of EBV as a trigger of MS.

  • 41.
    Jons, Daniel
    et al.
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Grut, Viktor
    Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, the Sahlgrenska Academy, Gothenburg, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bistrom, Martin
    Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Vrethem, Magnus
    Department of Neurology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Brenner, Nicole
    Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Staffan
    Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kockum, Ingrid
    The Karolinska Neuroimmunology & Multiple Sclerosis Center, Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Waterboer, Tim
    Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Olsson, Tomas
    The Karolinska Neuroimmunology & Multiple Sclerosis Center, Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Sundstrom, Peter
    Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.
    Andersen, Oluf Andersen
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Department of Clinical Neuroscience, Göteborg, Sweden.
    Epstein-Barr virus seroreactivity, putative autoimmunity and axonal injury in pre-symptomatic multiple sclerosis2023Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 29, nr Suppl. 3, s. 39-40Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Multiple sclerosis (MS) and presymptomatic axonal injury appears to develop only after an Epstein-Barr virus (EBV) infection. Anoctamin2 (ANO2), a chloride channel expressed in glial cells and neurons, was identified as a possible MS autoantigen. We here examine serum neurofilament (sNfL), a comprehensive EBV seroreactivity and antibodies against ANO2 in pre-symptomatic MS.

    Objectives/Aims: To study whether the appearance of EBV seroreactivity in the pre-symptomatic phase of MS precedes cumulating MS-induced neuroaxonal damage and whether it is associated with an incipient autoreactivity against a reported MS autoantigen (ANO2).

    Methods: We performed a case-control study with presymptomatic serum samples identified through cross-linkage of the Swedish MS register and Swedish biobanks. We assayed serum antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18 (VCAp18), EBV glycoprotein 350 (gp350), anoctamin 2 (ANO2), and serum neurofilament light (sNfL) in 669 pre-MS cases and matched controls.

    Results: EBNA1 seroreactivity increased in the pre-MS group from 20–15 years before MS onset, followed by gp350 seroreactivity (p=0.001–0.002, 15–10 years before onset). This appeared before the elevation of sNfL in EBV seropositive pre-MS cases (p=8⋅10-5, 10–5 years before onset). No significant sNfL increase was observed in the EBV seronegative group (p=0.95). Pre-MS cases with the highest sNfL levels cumulated in the EBV seropositive group (p=0.038). ANO2 seropositivity appeared virtually only in the EBNA1 seropositive group, in 16.7 % of EBNA1 seropositive pre-MS samples and in 10.0 % of corresponding controls (p=0.001). Combined EBNA1 and ANO2 seropositivity showed a higher association with subsequent MS than EBNA1 independent of ANO2 (p=0.002–0.028). In the EBNA1 seropositive stratum, ANO2 seropositivity was associated with 26% higher sNfL.

    Conclusion: In presymptomatic MS an antibody response against EBV, associated with ANO2 autoimmunity, was detectable before elevated sNfL, which cumulated in the EBV seropositive group. ANO2 seropositivity was associated with higher sNfL. An increase in ANO2 seroreactivity did not appear until after EBV seroconversion, limited to a subgroup of the EBV seropositive stratum. Thus, this specific cross-reaction could contribute to MS pathogenesis in a subgroup. This further implicates EBV in the pathogenesis of MS.

  • 42.
    Kågström, S.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbuker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Real-world longitudinal data of peginterferon beta-1a from a Swedish national post-marketing surveillance study (IMSE 6) - efficacy and safety profile2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 927-928Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. Phase II and III studies have shown that PegIFN reduces relapse rate and reduces the tendency to deteriorate disabilities. However, the long-term safety is important, therefore PegINF is included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study 6” (IMSE 6). Which characterizes the real-world profile of PegIFN, including efficacy, safety, tolerability and patient outcome parameters.

    Objectives: To follow-up the long-term safety and effectiveness of PegIFN in a real-world setting.

    Methods: Approximately 60 collaborating neurology clinics continuously recruited PegIFN patients and documented clinical and demographic data in the nationwide Swedish Neuro Registry (NeuroReg). Data were obtained from NeuroReg between June 2015 and April 2018 for the IMSE 6 study.

    Results: A total of 324 patients (78% female; 88% RRMS; mean age at treatments start 43 years) were followed up to 34 months (mean 15 months) with 26% treatment naïve and 49% switched from other injectables. Mean duration from initial symptom(s) to treatment start was 114 months, and 69 months from MS diagnosis to treatment start. In total, 169 patients discontinued for vari-ous reasons (60% adverse events, 24% lack of effect) and switched mainly to rituximab (63 patients, 37%). The discontinuation rate at 12 months was 42.6%. Relapses before treatment were reduced from 207 to 130/1000 patient years during treatment. With 55% having no relapse and 9% having 1 relapse during treatment period (35% missing data). After 12 months, all clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life - 5-Dimension test (EQ-5D), Visual Analogue Score (VAS), and the mean Symbol Digit Modalities Test (SDMT)) remained stable. A total number of 9 adverse events (6 serious: 1 gastrointestinal disorder, 2 general disorder and administrations site, 2 skin, 1 reproductive) were reported to Swedish Medical Product Agency (MPA).

    Conclusions: NeuroReg proves to function well as a post-marketing drug surveillance platform, providing data regarding drug effectiveness and AEs. This real-world study presentation from IMSE 6 shows a stable efficacy and safety profile in long-term clinical use.

  • 43.
    Kågström, S.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Demirbüker, S. Safer
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Martin, C.
    Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)2018Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 699-700Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for determination of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study 1” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).

    Objective: To follow-up the long-term safety and effectiveness of NTZ in a real-world setting.

    Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures are registered prospectively.

    Results: 3052 patients (72% female; 82% RRMS; mean age at treatment start 36 years; mean treatment duration 45.9 months) have been included in IMSE 1 from August 2006 until April 2018. A total of 1234 RRMS patients where included year ≥2011 (JCV test introduction) and had information on JCV (482 anti-JCV anti-bodies (JCV+), 752 JCV negative (JCV-)). 691 of these patients were currently treated with NZT at cutoff date, 88 (13%) of which were JCV+ with a mean JCV index at 1.1±1.1. A total of 612/1234 (49%) discontinued NTZ treatment at some time point of which 266/403 (66%) JCV+ discontinued due to JCV+. JCV- patients mainly discontinued due to pregnancy/planning pregnancy (78/209, 37%) and other reasons (57/209, 27%). The one and two-year drug survival rate was 79% and 45% for JCV+ and 90% and 82% for JCV-. The overall drug survival rate was 16% for JCV+ and 72% for JCV-. In patients with continuous NTZ treatment for ≥2 years (n=738), long lasting stabilization of disease activity was observed. From year 2006 until cutoff, 96 Serious AEs had been reported to the Swedish MPA and included 8 cases (1 fatal) of progressive multifocal leukoencephalopathy (PML), reported between 2008 and 2012. A total of 14 patients have died during or within 6 months after NTZ discontinuation, as reported in NeuroReg. None were reported to be associated to NTZ.

    Conclusions: NeuroReg functions well as a post-marketing drug surveillance platform, providing long-term data on drug effects and AEs. NTZ is generally well tolerated with sustained effective-ness. The introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a reduced incidence of PML.

  • 44.
    Kågström, S.
    et al.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fält, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Forsberg, L.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Berglund, A.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hillert, J.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, P.
    Department of Neurology, Lund University, Lund, Sweden.
    Dahle, C.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Lycke, J.
    Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg, Göteborg, Sweden.
    Landtblom, A. -M
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Burman, J.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Martin, C.
    Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Neurology.
    Piehl, F.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Improved clinical outcomes in patients treated with natalizumab for at least 8 years - real-world data from a Swedish national post-marketing surveillance study (IMSE 1)2019Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 763-764Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. To this end the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (Aug 2006).

    Objective: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting.

    Methods: In Sweden MS patients are registered in the nationwide Swedish Neuro Registry (NeuroReg). IMSE 1 includes patients starting NTZ treatment and data is collected from NeuroReg. Adverse events (AEs), JC-virus status (JCV) and clinical effec-tiveness measures are registered prospectively.

    Results: A total of 3141 patients were included in the IMSE 1 study from August 2006 until April 2019 (72% female; men age 35 years; 79% RRMS; mean treatment duration 50 months) and 288 had been treated for at least 96 months. 71% of these 288 patients (71% female; men age 37 years; 82% RRMS; mean treatment duration 118 months) were treated with interferons and glatiramer acetate prior NTZ. At some point of time, 31% (90/288) discontin-ued NTZ treatment of which 41% discontinued due to JCV posi-tive (JCV+). In total, 30% (86/288) of these patients were JCV+with a mean JCV index of 1.2±1.0 (6% missing data). Relapses before treatment were reduced from 388/1000 patient years to 54 during treatment, 62% were relapse-free and 17% had 1 relapse during the entire treatment period (12% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT)) showed statistically significant improvement between baseline and 96 months. Over the entire observation time, 104 Serious AEs had been reported to the Swedish MPA and included 9 cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which 8 between 2008 and 2012, and 1in 2018. 16 patients died during or within 6 months of last NTZ infusion. None were judged to be directly associated with NTZ.

    Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control. Introduction of JCV testing has led to fewer treated JCV+ patients, which likely explains a drastic drop in the incidence of PML.

  • 45.
    Kågström, S.
    et al.
    Karolinska Institutet, Solna, Sweden.
    Leandersson, Å.
    Karolinska Institutet, Solna, Sweden.
    Forsberg, L.
    Karolinska Institutet, Solna, Sweden.
    Berglund, A.
    Karolinska Institutet, Solna, Sweden.
    Hillert, J.
    Karolinska Institutet, Solna, Sweden.
    Nilsson, P.
    Lund University, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Danderyd, Sweden.
    Lycke, J.
    Institute of Neuroscience and Physiology, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Sundström, P.
    Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Institutet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Solna, Sweden.
    Real-world data of peginterferon beta-1a from a swedish national post-marketing surveillance study (IMSE 6) - effectiveness and safety profile2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 302-302Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Subcutaneous peginterferon beta-1a (PegIFN) was approved for relapsing-remitting multiple sclerosis (RRMS) in Europe 2014. The clinical trial program showed that PegIFN reduced the relapse rate and proportion with disability progression compared to placebo. At its launch in Sweden, PegIFN was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 6), providing possibilities to track long-term effectiveness and safety in a population-based setting.

    Objectives: To follow-up the long-term effectiveness and safety of PegIFN treatment in Swedish patients in a real-world context.

    Methods: Data was obtained from the nationwide Swedish Neuro Registry (NeuroReg) between June 2015 and May 2020. Effectiveness measures were assessed using the Wilcoxon Signed Rank Test and drug survival using the Kaplan-Meier curve.

    Results: A total of 364 patients (78% female; 87% RRMS; mean age at treatments start 43 years) were followed up to 57 months (mean 20 months), of which 200 (55%) patients had been treated for at least 12 months. The majority of the patients had switched from other injectables (164 patients, 45%) or were treatment naïve (90 patients, 25%) prior to treatment with PegIFN. Over the dura-tion of the follow-up, 68% (247/364) patients discontinued their PegIFN treatment for various reasons (60% adverse events, 24% lack of effect) and switched mainly to rituximab (105 patients, 43%). The overall drug survival was 32%, 40% for men and 30% for women. The one- and two-year drug survival rate was 57% and 40%, respectively. The mean number of relapses were reduced from 0.35 one year before treatment start to 0.11 one year after (35% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5-Dimension test (EQ-5D), Visual Analogue Score (VAS) and Symbol Digit Modalities Test (SDMT)) remained stable. Statistically significant changes were observed in SDMT (p=0.027). A total number of 18 adverse events (6 serious) were reported to Swedish Medical Product Agency.

    Conclusions: These findings are consistent with PegIFN being a safe disease modifying treatment, however, a relatively high pro-portion of patients switched due to adverse events. All clinical effectiveness measures remained stable in patients treated with PegIFN for at least 12 months in this nationwide population-based real-world study. Longer follow up is needed to address the long-term effectiveness.

  • 46.
    Kågström, S.
    et al.
    Karolinska Institutet, Solna, Sweden.
    Leandersson, Å.
    Karolinska Institutet, Solna, Sweden.
    Forsberg, L.
    Karolinska Institutet, Solna, Sweden.
    Berglund, A.
    Karolinska Institutet, Solna, Sweden.
    Hillert, J.
    Karolinska Institutet, Solna, Sweden.
    Nilsson, P.
    Lund University, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Danderyd, Sweden.
    Lycke, J.
    Institute of Neuroscience and Physiology, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Sundström, P.
    Umeå University, Umeå, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Institutet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Solna, Sweden.
    Efficacy and safety in patients treated with natalizumab for at least 10 years - real-world data from a swedish national surveillance study (IMSE 1)2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 279-280Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Natalizumab (NTZ) is a highly effective disease modulatory treatment for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important for evalua-tion of long-term safety and effectiveness in a real-world setting. To this end, the “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE 1) was initiated upon NTZ launch in Sweden (August 2006).

    Objectives: To follow-up the long-term effectiveness and safety of NTZ in a real-world setting, with focus on patients treated at least 10 years.

    Methods: IMSE 1 includes patients starting NTZ treatment and data is collected from the nationwide Swedish Neuro Registry (NeuroReg). Adverse events (AEs), JC-virus status (JCV) and clinical effectiveness measures are registered in NeuroReg pro-spectively. Effectiveness measures were assessed using the Wilcoxon Signed Rank Test.

    Results: A total of 3291 patients were included in the IMSE 1 study from August 2006 until June 2020 (72% female; mean age 36 years; 80% RRMS; mean treatment duration 50 months). 171/3291 patients (5%) had been treated for at least 120 months (73% female; men age 36 years; 87% RRMS; mean treatment duration 139 months). A total of 64% (110/171) were treated with interferons or glatiramer acetate prior to NTZ treatment. Over the duration of follow-up discontinued 21% (35/171) their NTZ treat-ment of which 46% (16/35) discontinued due to JCV positive (JCV+). In total, 27% (46/171) of these patients were JCV+ with a mean JCV index of 1.2±1.0 (4% missing data). The mean num-ber of relapses were reduced from 0.84 one year before NTZ treat-ment start to 0.00 during the first treatment year (12% missing data). All clinical effectiveness measures (Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Multiple Sclerosis Impact Scale (MSIS-29) and Symbol Digit Modalities Test (SDMT)) showed improvement in mean between baseline and 120 months. However, only MSSS, MSIS-29 psy-chological and SDMT were statistically significant. Over the entire observation time, 114 Serious AEs had been reported to the Swedish Medical Product Agency and included nine cases (2 fatal) of progressive multifocal leukoencephalopathy (PML) of which eight between year 2008 and 2012, and one in 2018. 17 patients died during or within 6 months of last NTZ infusion. None were judged to be directly associated with NTZ.

    Conclusions: NTZ is generally well tolerated with sustained effectiveness regarding cognitive, physical and psychological measures, as well as relapse-control.

  • 47.
    Larsson, Veronica
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Forsberg, Linda
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Hillert, Jan
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, Petra
    Lund University, Department of Neurology, Lund, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Clinical Immunology, Linköping, Sweden.
    Svenningsson, Anders
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Lycke, Jan
    University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden.
    Landtblom, Anne-Marie
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    Burman, Joachim
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    Martin, Claes
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Sundström, Peter
    Umeå University, Department of Clinical Science, Neurosciences, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Piehl, Fredrik
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Olsson, Tomas
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Clinical Effectiveness and Safety of Cladribine Tablets for Patients Treated at least 24 Months in the Swedish post-market surveillance study "Immunomodulation and Multiple Sclerosis Epidemiology 10"(IMSE 10)2023Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 29, nr Suppl. 3, s. 616-616, artikel-id P715/1951Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Cladribine is a deoxyadenosine analogue prodrug targeting proliferating B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with remitting multiple sclerosis (RMS). CladT is included in the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology substudy 10” (IMSE 10).

    Objectives/Aims: To assess safety and effectiveness of CladT with focus on 24 months treatment outcomes.

    Methods: Data on Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life -5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) scores, and relapses and Adverse Events (AEs) were collected from the nationwide Swedish Neuro Registry (NeuroReg). Effectiveness measures and relapse rates were assessed using Wilcoxon Signed Rank Test.

    Results: A total of 287 CladT exposed Persons with MS (PwMS) have been included in IMSE 10 since the launch of CladT in April 2018. In this cohort 90.6% remained with CladT while 27 patients (9%) discontinued treatment at any time after initiation. The most common reason for discontinuation was lack of effect (78%). A total of 24 AEs were reported to the Swedish Medical Products Agency, of which 10 were serious. The most common AE reported were infection and infestation.A total of 137 patients had CladT exposure for ⩾24 months of which 30 % being treatment naïve, 19% switched from Tysabri, 10 % from dimethyl fumarate and 7% from rituximab, prior CLadT treatment. In this cohort 91.9% remained with CladT. The ⩾24 months’ cohort demonstrated clinical stability with a non-significant trend for improvement in mean MSSS, SDMT, MSIS-29 Psychological/Physical scores compared with baseline. All other outcomes remained stable. The mean annual relapse rate (ARR) decreased significantly (p<0.05) during all treatment years compared to the ARR one-year prior treatment.Lymphocyte levels decreased from a mean of 1.9 x 109/L at treatment start to 1.11 x 109/L at 12 Months and 0.87 x 109/L at 24 months of treatment.

    Conclusion: Most PwMS exposed for ⩾24 months to CladT display clinical stability and a tendency for improvement compared with baseline in several of the investigated outcomes. Longer observation times will be needed to assess the effectiveness and safety of CladT beyond 24 month exposure.

  • 48.
    Larsson, Veronica
    et al.
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
    Nilsson, Petra
    Lund University, Department of Neurology, Lund, Sweden.
    Magdalena, Lucia Alonso
    Skåne University, Department of Neurology, Skåne University Hospital; Department of Clinical Sciences, Lund University, Skåne, Sweden.
    Svenningsson, Anders
    Danderyd Hospital, Department of Clinical Science, Stockholm, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Neurology.
    Ayad, Ahmad
    Capio S:t Göran Hospital, Neurologiska kliniken, Stockholm, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Linköping.
    Burman, Joachim
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    Lycke, Jan
    University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden.
    Piehl, Fredrik
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; Academic Specialist Center, Centrum for Neurology, Stockholm, Sweden.
    Fink, Katharina
    Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden; Academic Specialist Center, Centrum for Neurology, Stockholm, Sweden.
    CLADCOMS- CLADribine tablets long-term Control Of MS - a post-marketing investigator driven study2023Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 29, nr Suppl. 3, s. 968-969, artikel-id P1518/2240Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Cladribine is a deoxyadenosine analogue prodrug that induces immune reconstitution by selectively targeting B- and T-lymphocytes. Cladribine tablets (CladT) are administered in two courses, 12 months apart, for patients with relapsing multiple sclerosis (RMS). Post-marketing surveillance is important for evaluation of long-term safety and effectiveness in a real-world setting. CLADCOMS (CLADribine tablets long-term Control Of MS) is a post-marketing investigator driven study. Here we report two year prospectively obtained data on the first 100 patients included in the study until April 2021.

    Objectives/Aims: To investigate number of patients free of disease activity until April 2023 among the first 100 RMS patients included.

    Methods: CLADCOMS includes patients with RMS from eight academic neurology clinics of Sweden starting Cladribine treatment after 23rd of March 2018. Data was prospectively registered in the Swedish Neuroregistry using highly structured yearly follow-up routines. Descriptive data on relapses, MRI activity, and Patient Reported Outcome Measures from the first 100 patient included in the study were obtained from the registry.

    Results: By April 2023, 206 patients were included in the CLADCOMS study. In April 2021 the first 100 patients had entered the study including 30% treatment naïve, 26% switched from natalizumab, 10% from dimethyl fumarate and 7% from rituximab. After the first two years after treatment initiation 87% were relapse free. MRI-activity during the first two years after treatment initiation will be analyzed.Analysis of CD19+ B-cells counts over time showed a significant drop from baseline before first dose (0.38x109/L ±0.68) to year one (0.15x109/L ±0.12) and year two (0.13x109/L ±0.09). The proportion of memory B-cells dropped from 11.8% ±9.33% at baseline to 3.0% ±2.8% after the first year and to 2.6% ±2.4% after the second year of treatment. The proportions of naïve B-cells raised over time from 61% ±18.3% at baseline to 76.8% ±18.7 year one and 78.6% ±12.3 after two years of treatment.

    Conclusion: CladT treatment demonstrates clinical stability during the first two years after treatment initiation. The unique immune depletion helps to explain the durability of effects of Cladribine. However, continued follow-up is needed to assess the effectiveness and safety of treatment with Cladribine to investigate time to disease re-activation after full treatment.

  • 49.
    Leandersson, Å.
    et al.
    Karolinska Institutet, Solna, Sweden.
    Kågström, S.
    Karolinska Institutet, Solna, Sweden.
    Forsberg, L.
    Karolinska Institutet, Solna, Sweden.
    Hillert, J.
    Karolinska Institutet, Solna, Sweden.
    Nilsson, P.
    Lund University, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Danderyd, Sweden.
    Lycke, J.
    University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Sundström, P.
    Umeå University, Umea, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Institutet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Solna, Sweden.
    A swedish post-market surveillance study of the long-term effectiveness and safety of alemtuzumab (imse 3) for patients treated for at least 36 months2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 252-253Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Alemtuzumab (ALZ) is an approved disease-modi-fying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Post-marketing surveillance is important to assess the long-term safety and effectiveness in a real-world setting. ALZ has therefore been included into the Swedish post-market surveillance study “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) upon launch in Sweden (March 2014).

    Objectives: To track effectiveness and long-term safety of ALZ in a real-world setting, with focus on patients treated with ALZ for at least 36 months.

    Methods: Swedish MS patients are registered into the nationwide Swedish MS Registry (NeuroReg). IMSE 3 includes all patients starting ALZ treatment with annual clinical measures obtained from NeuroReg; Extended Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), Symbol Digit Modalities Test (SDMT), Multiple Sclerosis Impact Scale (MSIS-29), European Quality of Life – 5 Dimension Test (EQ-5D) and Visual Analogue Scale (VAS).

    Results: A total of 118 patients (59% female; 95% RRMS) were included in IMSE 3 between March 2014 and June 2020. Out of 118 patients, 93 had been treated for at least 36 months (62% female), of which 10 patients had switched to another DMT. Mean age at treatment start for patients treated ⩾ 36 months was 34 years and mean treatment duration was 54 months. Mean number of drugs prior ALZ initiation was 2.4. Most of the patients (40%, n=37) switched to ALZ from natalizumab or were treatment naïve (13%, n=12) prior ALZ. The mean num-ber of relapses was reduced from 0.72 one year before ALZ initiation to 0.10 during the first treatment year, followed by 0.08 the second treatment year and 0.06 the third year of ALZ treatment (n=79, 15% missing data). In patients treated ⩾ 36 months significant improvements in mean baseline compared to 36 months were seen for MSSS (3.3 ± 2.7 to 2.3 ± 2.3, n=44) and EQ-5D (0.7 ± 0.3 to 0.8 ± 0.3, n=50), while SDMT showed significantly worsened results after 36 months (64.8 ± 17.5 to 56.2 ± 12.7, n=59). EDSS, MSIS-29 and VAS scores remained stable. A total of 36 adverse events were reported to the Swedish Medical Products Agency, 13 events were classified as serious and 23 events as non-serious. Two patients died during ALZ treatment, one of which was associated to ALZ treatment, and died in association with the first ALZ treatment cycle due to fulminant viral hepatitis.

    Conclusions: Patients treated with ALZ for at least 36 months improved or remained stable across all effectiveness measures except SDMT. Continued follow-up is needed to address long term effectiveness and safety of ALZ.

  • 50.
    Leandersson, Å.
    et al.
    Karolinska Instituet, Solna, Sweden.
    Kågström, S.
    Karolinska Instituet, Solna, Sweden.
    Forsberg, L.
    Karolinska Instituet, Solna, Sweden.
    Hillert, J.
    Karolinska Instituet, Solna, Sweden.
    Nilsson, P.
    Lund University, Lund, Sweden.
    Dahle, C.
    Linköping University, Linköping, Sweden.
    Svenningsson, A.
    Danderyd Hospital, Danderyd, Sweden.
    Lycke, J.
    University of Gothenburg, Gothenburg, Sweden.
    Landtblom, A. -M
    Uppsala University, Uppsala, Sweden.
    Burman, J.
    Uppsala University, Uppsala, Sweden.
    Martin, C.
    Danderyd Hospital, Danderyd, Sweden.
    Sundström, P.
    Umeå University, Umeå, Sweden.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Piehl, F.
    Karolinska Instituet, Solna, Sweden.
    Olsson, T.
    Karolinska Institutet, Solna, Sweden.
    Relation of edss to patient-reported outcome measurements in ms: real-world data from a swedish nationwide study of fingolimod (imse 2)2020Ingår i: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 26, nr 3 Suppl., s. 187-188Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis, introduced in Sweden 2011. Already from launch, FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort.

    Objectives: To assess the relation between Expanded Disability Status Scale (EDSS) and patient-reported outcome measurements (PROMS) in patients treated with FGL.

    Methods: Swedish MS patients are registered into the nation-wide Swedish MS Registry. Demographic data, EDSS and the Multiple Sclerosis Impact Scale (MSIS-29), Symbol Digit Modalities Test (SDMT), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) were collected for FGL patients who agreed to participate in the IMSE 2 study. Spearman rank correlation were used to determine associations between EDSS and PROMS.

    Results: From September 2011 until June 2020, 1670 MS patients (68% female) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 44 months (M). Out of 1670 patients, 560 (63% female) had been treated with FGL for at least 60 M. Mean age was 40 years and mean treatment duration 81 M. Significant (p<0.05) correla-tions was found between EDSS and all PROMs. The strongest correlation was found between the physical component of MSIS-29 for both baseline (r=0.60, n=778) and 60 M (r=0.64, n=109). Also, for both EQ-5D and VAS, Spearman coefficient indicates a moderate correlation for baseline (EQ-5D; r=-0.48, n=744 and VAS; -0.43, n=706) and 60 M (EQ-5D; r=-0.47, n=102 and VAS; -0.48, n=102) respectively. The correlation between EDSS and SDMT and the psychological component of MSIS-29, both indi-cated a weak correlation for baseline (SDMT; r=-0.28, n=771 and MSIS-29 psychological; r=0.28, n=778). For 60 M the correla-tions were stronger and indicated a moderate correlation (SDMT; r= -0.42, n=114 and MSIS-29 psychological; r=0.33, n=109).

    Conclusions: The observed correlations between EDSS and PROMs in patients treated with FGL indicate a weak correlation with SDMT and the psychological component of MSIS-29. These results highlight that different scales capture different dimensions of the physical and psychological impact of MS from the patient’s perspective and have important functions which should continue to be followed.

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