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  • 1.
    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, 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.

  • 2.
    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, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 1001-1002Artikel i tidskrift (Övrigt vetenskapligt)
  • 3.
    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, 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.

  • 4.
    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, 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.

  • 5.
    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, 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.

  • 6.
    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, 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.

  • 7.
    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, 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

  • 8.
    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, 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.

  • 9.
    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, 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.

  • 10.
    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, 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.

  • 11.
    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, 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.

  • 12.
    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, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 7, s. 992-993Artikel i tidskrift (Övrigt vetenskapligt)
  • 13.
    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, 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.

  • 14.
    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, 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.

  • 15.
    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, 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.

  • 16.
    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, 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.

  • 17.
    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, 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.

  • 18.
    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, 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.

  • 19.
    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 MS2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, artikel-id 1352458519866600Artikel 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.

  • 20.
    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, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 11, s. 45-45Artikel i tidskrift (Övrigt vetenskapligt)
  • 21.
    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, 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.

  • 22.
    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, 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.

  • 23.
    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, 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.

  • 24.
    Montgomery, Scott
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology and Biostatistics, Örebro University Hospital and Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Lee, S.
    Celgene Corporation, Summit NJ, United States.
    Minton, N.
    Celgene Corporation, Summit NJ, United States.
    Castelo-Branco, A.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Chiesa, F.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Conte, S.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Rosenlund, M.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Niemcryk, S.
    Celgene Corporation, Summit NJ, United States.
    Lindholm, A.
    Celgene Corporation, Summit NJ, United States.
    Piehl, F.
    Department of Neurology, Karolinska University Hospital, Solna, Sweden.
    Infections in patients with multiple sclerosis: a nationwide cohort study in Sweden2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 388-388Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Previous studies suggest that susceptibility to infections is not raised among multiple sclerosis (MS) patients in general, but certain specific infections, such as those of the urinary or respiratory tract, are more common in patients with higher disability. However, contemporary MS cohorts to a higher degree are treated with newer disease-modifying treatments (DMTs) that exert stronger effects on the immune defence. Here we investigated the rate of infections in patients before and after MS diagnosis as compared with a matched MS-free population.

    Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched to 10 MS-free individuals by age, sex, and region of residence. Incidence rates per 10,000 person-years and incidence rate ratios (IRRs) of first infection by site and type were calculated after the MS diagnosis date.

    Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). During the year before MS diagnosis, MS patients showed higher proportions of urinary and kidney infections, meningitis and encephalitis, and bacterial infections compared with the MS-free cohort.After MS diagnosis, an increased risk of non-serious (IRR 1.65; 95% CI 1.56-1.75) and serious (admitted to hospital) infections (IRR 2.59; 95% CI 2.33-2.89) was detected among MS patients relative to the MS-free cohort. The risk of some bacterial (IRR 2.23; 95% CI 1.98-2.52) and some viral infections (IRR 1.70; 95% CI 1.48-1.96) was higher in MS patients of both sexes while only males showed an increased risk of fungal infections (IRR 1.91; 95% CI 1.26-2.89). Relative to the MS-free cohort, MS patients had an increased risk of all infection types, such as meningitis and encephalitis (IRR 6.16; 95% CI 4.47-8.48), other opportunistic infections (IRR 2.72; 95% CI 2.08-3.55), urinary and kidney infections (IRR 2.44; 95% CI 2.24-2.66), herpes virus (IRR 2.32; 95% CI 1.77-3.05), pneumonia and influenza (IRR 1.92; 95% CI 1.66-2.23), and skin infections (IRR 1.89; 95% CI 1.65-2.16).

    Conclusions: After MS diagnosis, patients had higher incidences of non-serious and serious infections compared with a cohort without MS. MS patients had an increased risk of being diagnosed during follow-up with most infection types compared with controls. This risk was particularly high for meningitis and encephalitis.

  • 25.
    Montgomery, Scott
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology and Biostatistics, Örebro University Hospital and Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Lee, S.
    Celgene Corporation, Summit NJ, United States.
    Minton, N.
    Celgene Corporation, Summit NJ, United States.
    Castelo-Branco, A.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Chiesa, F.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Conte, S.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Rosenlund, M.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Niemcryk, S.
    Celgene Corporation, Summit NJ, United States.
    Lindholm, A.
    Celgene Corporation, Summit NJ, United States.
    Piehl, F.
    Department of Neurology, Karolinska University Hospital, Solna, Sweden.
    Risk of osteoporosis and fractures in patients with multiple sclerosis: a nationwide cohort study in Sweden2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 387-388Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: While multiple sclerosis (MS) is usually diagnosed in young adults, many individuals living with the diagnosis are above age 40 years. Osteoporosis and fractures, which are morbidities generally associated with ageing but also physical inactivity, were determined in patients before and after MS diagnosis and compared with a matched MS-free population.

    Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register and matched with 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years and incidence rate ratios (IRRs; vs the MS-free cohort) of osteoporosis and fractures by sex and age at event were calculated after MS diagnosis based on ICD-10 codes from inpatient and outpatient specialist care.

    Results: In total, 6,602 MS patients were identified and compared with 61,828 without MS (female, 69%; median age, 40 years). Before MS diagnosis, MS patients showed significantly increased proportions of osteoporosis (0.5% vs 0.3%) and fractures (12.6% vs 11.4%) compared with the MS-free cohort.After diagnosis, MS patients had an increased risk of osteoporosis (IRR 1.69; 95% confidence interval [CI] 1.22-2.35). The increased risk of osteoporosis among MS patients was observed for both sexes (females, IRR 1.60; 95% CI 1.13-2.28 and males, IRR 2.56; 95% CI 1.04-6.31), as well as in the older age strata 40-59 years (IRR 2.39; 95% CI 1.47-3.89) and ⩾60 years (IRR 1.69; 95% CI 1.06-2.70), but not among those aged < 40 years. Similarly, an increased risk of fractures among MS patients (IRR 1.37; 95% CI 1.24-1.51) was shown for both females (IRR 1.40; 95% CI 1.25-1.58) and males (IRR 1.29; 95% CI 1.07-1.55), as well as the age strata 40-59 years (IRR 1.52; 95% CI 1.31-1.76) and ⩾60 years (IRR 1.92; 95% CI 1.58-2.33), but not those aged < 40 years.

    Conclusions: The risk of osteoporosis and fractures was moderately increased in MS patients of both sexes and in the older age groups, which may relate to physical inactivity and an increased risk of falls.

  • 26.
    Nilsagård, Ylva
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län.
    Gunn, H.
    University of Plymouth, Plymouth, England.
    Freeman, J.
    University of Plymouth, Plymouth, England.
    Hoang, P.
    University of NSW, Sydney, Australia.
    Lord, S.
    University of NSW, Sydney, Australia.
    Mazumder, Rajarshi
    Oregon Health and Science University, Portland, USA.
    Cameron, Michelle
    Oregon Health and Science University, Portland, USA.
    Falls in people with MS-an individual data meta-analysis from studies from Australia, Sweden, United Kingdom and the United States2015Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 21, nr 1, s. 92-100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Falls are common in people with multiple sclerosis (PwMS). Previous studies have generally included small samples and had varied methods.

    Objectives: The objectives of this paper are to compile fall rates across a broad range of ages and disease severity and to definitively assess the extent to which MS-associated and demographic factors influence fall rates.

    Methods: Individual data from studies in four countries that prospectively measured falls for three months were analyzed. We determined fall rates, prevalence of fallers (1 falls) and frequent fallers (2 falls), location and timing of falls, and fall-related demographic factors.

    Results: A total of 537 participants reported 1721 falls: 56% were fallers and 37% frequent fallers. Most falls occurred indoors (65%) between 6 a.m. and 6 p.m. (75%). Primary progressive MS was associated with significantly increased odds of being a faller (odds ratio (OR) 2.02; CI 1.08-3.78). Fall risk peaked at EDSS levels of 4.0 and 6.0 with significant ORs between 5.30 (2.23-12.64) and 5.10 (2.08-12.47). The fall rate was lower in women than men (relative risk (RR) 0.80; CI 0.67-0.94) and decreased with increasing age (RR 0.97 for each year, CI 0.95-0.98).

    Conclusion: PwMS are at high risk of falls and there are important associations between falls and MS-associated disability, gender and age.

  • 27.
    Nilsagård, Ylva
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Ctr Hlth Care Sci, Örebro Univ Hosp, Örebro, Sweden.
    Westerdahl, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Wittrin, A.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning.
    Correlation between maximal walking distance and self-rated limitations in walking2014Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, nr 7, s. 992-992Artikel i tidskrift (Övrigt vetenskapligt)
  • 28.
    Piehl, F.
    et al.
    Department of Neurology, Karolinska University Hospital, Solna, Sweden.
    Castelo-Branco, A.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Chiesa, F.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Conte, S.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Rosenlund, M.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Lee, S.
    Celgene Corporation, Summit NJ, United States.
    Minton, N.
    Celgene Corporation, Summit NJ, United States.
    Niemcryk, S.
    Celgene Corporation, Summit NJ, United States.
    Lindholm, A.
    Celgene Corporation, Summit NJ, United States.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology and Biostatistics, Örebro University Hospital and Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Cardiovascular disease in patients with multiple sclerosis: a nationwide cohort study in Sweden2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 49-50Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: The cardiovascular disease (CVD) rate among multiple sclerosis (MS) patients has been shown to be elevated; however, studies involving more recently diagnosed patients are rare. Here we estimated the rate of CVD in patients before and after MS diagnosis as compared with a matched MS-free population.

    Methods: Incident MS patients diagnosed in 2008-2016 were identified in the Swedish National Patient Register. MS patients were matched with 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years (PY) and incidence rate ratios (IRR) of cardiovascular outcomes were calculated after MS diagnosis (equivalent date for those without MS) and among those with no history of CVD before this date.

    Results: In total, 6,602 MS patients and 61,828 without MS (female, 69%; median age, 40 years) were identified. Before MS diagnosis, patients showed higher proportions of stroke (2.0% vs 0.6%), transient ischaemic attack (TIA) (0.4% vs 0.2%) and peripheral vascular disease (0.3% vs 0.2%) compared with the MS-free cohort. The year before MS diagnosis, larger proportions were prescribed diuretics (8.4% vs 6.9%), peripheral vasodilators (1.4% vs 1.0%), lipid-modifying agents (5.6% vs 4.8%), and calcium channel blockers (3.7% vs 3.1%).After MS diagnosis, patients had a higher risk of major adverse cardiovascular events (MACE) (IRR 1.35; 95% confidence interval [CI] 1.06-1.71), heart failure (HF) (IRR 1.36; 95% CI 1.02-1.80), and TIA (IRR 1.59; 95% CI 1.05-2.42) compared with the MS-free cohort. The risk of bradycardia (IRR, 2.61; 95% CI 1.14-5.97) was higher only in MS patients with no history of CVD. CVD incidence rates in MS patients were comparable between sexes except for the HF rate, which was higher among males (28.28 per 10,000 PY, 95% CI 18.79-40.87) than females (11.81 per 10,000 PY, 95% CI 7.71-17.30). The relative risk of MACE (IRR 2.40; 95% CI 1.15-5.00), TIA (IRR 7.03; 95% CI 2.62 -18.87), HF (IRR 3.28; 95% CI 1.46-7.37), and bradycardia (IRR 4.51; 95% CI 1.54-13.20) were higher among younger MS patients (aged < 40 years at diagnosis).

    Conclusions: After MS diagnosis, MS patients showed an increased incidence of MACE, TIA, and HF compared with those without MS, irrespective of CVD history. The age-matched rela-tive risk was particularly high among younger MS patients. In particular, the relative risk of bradycardia was only higher among younger patients and patients with no history of CVD.

  • 29.
    Piehl, F.
    et al.
    Department of Neurology, Karolinska University Hospital, Solna, Sweden.
    Castelo-Branco, A.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Chiesa, F.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Conte, S.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Rosenlund, M.
    Real-World Insights, IQVIA Nordics, Solna, Sweden.
    Lee, S.
    Celgene Corporation, Summit NJ, United States.
    Minton, N.
    Celgene Corporation, Summit NJ, United States.
    Niemcryk, S.
    Celgene Corporation, Summit NJ, United States.
    Lindholm, A.
    Celgene Corporation, Summit NJ, United States.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology and Biostatistics, Örebro University Hospital and Örebro University, Örebro, Sweden; Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Risk of comorbidity in patients with multiple sclerosis: a nationwide cohort study in Sweden2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 102-102Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Substantial progress in the treatment of multiple sclerosis (MS) has been made since the 1990s. However, the presence of comorbidity and the impact of treatment are less defined. Here we determined rates of comorbidity before and after MS diagnosis as compared with a matched MS-free population.

    Methods: A national incident MS cohort diagnosed in 2008-2016 was identified in the Swedish National Patient Register with data further linked to the national Prescribed Drug Register and Cause of Death Register. In addition, a sub-cohort of MS patients was identified in the electronic medical records (EMR) of the Karolinska University Hospital. MS patients were matched with and compared to 10 MS-free individuals by age, sex, and region of residence. Incidence rates (IR) per 10,000 person-years and incidence rate ratios (IRR) of comorbidities were calculated after MS diagnosis.

    Results: In total, 6,602 MS patients were identified in the national cohort and were compared with 61,828 MS-free controls (female, 69%; median age, 40 years), while a sub-cohort from one hospital of 1,289 patients had a MS diagnosis recorded in EMR and was compared with 11,721 individuals without MS (female, 68%; median age, 37 years). The national MS cohort had higher proportions before MS diag-nosis compared with MS-free controls of autoimmune disease (1.3% vs 0.7%), bladder dysfunction (1.2% vs 0.2%), retinal disorders (2.4% vs 1.2%) and epilepsy (1.5% vs 0.8%). Similar patterns were observed for the single-hospital cohort, except for epilepsy. Bipolar disorder was more common among single-hospital MS patients (1.6% vs 0.7%).After MS diagnosis, patients in the national cohort had higher IR compared with MS-free controls of autoimmune disease (IRR 3.60; 95% confidence interval [CI], 2.88-4.51), bladder dysfunction (IRR 47.44; 95% CI, 36.81-61.14) and epilepsy (IRR 2.36; 95% CI, 1.75-3.17). Similar patterns were observed in the single-hospital cohort. Toxic liver disease was higher (IRR 3.51; 95% CI 1.37-8.98) in the MS cohort in the national cohort only, while bipolar disorder was higher only in the single-hospital cohort (IRR 1.88; 95% CI 1.10-3.22).

    Conclusions: Before a diagnosis of MS, patients already displayed an increased rate of comorbidity compared with MS-free controls. After diagnosis, patients with MS continued to display increased risk of several comorbidities, some of which may be explained by surveillance bias due to more frequent contact with healthcare.

  • 30.
    Roshanisefat, H.
    et al.
    Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden; Neuroimmunology Unit, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Bahmanyar, S.
    Clinical Epidemiology Unit and Center for Pharmacoepidemiology, Karolinska University Hospital, Stockholm, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
    Hillert, J.
    Neuroimmunology Unit, Karolinska Institute, Stockholm, Sweden.
    Olsson, T.
    Neuroimmunology Unit, Karolinska Institute, Stockholm, Sweden.
    Montgomery, Scott M.
    Clinical Epidemiology Unit and Center for Pharmacoepidemiology, Karolinska University Hospital, Stockholm, Sweden; Department of Primary Care and Public Health, Charing Cross Hospital, London, UK.
    Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis2012Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 18, nr 10, s. 1430-1436Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Comorbid inflammatory conditions in multiple sclerosis (MS) patients suggest shared risks with MS.

    Objective: To estimate if the risk of immune-mediated disease in MS patients and their parents is increased.

    Methods: Swedish register data were analysed using Cox regression to estimate immune-mediated disease risk among 11284 fathers and 12006 mothers of MS patients, compared with 123158 fathers and 129409 mothers of index subjects without MS. Similar analyses were conducted among 20276 index subjects with MS and 203951 without.

    Results: Parents of patients with MS did not have a significantly altered immune-mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn's disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset.

    Conclusion: The increased occurrence of other immune-mediated diseases in MS patients may not be due to shared genetic factors and surveillance bias is likely to be the main or possibly the entire explanation. If not entirely explained by surveillance bias, a modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics.

  • 31.
    Smith, K. A.
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Sweden; Department of Translational Epidemiology, Institute of Environmental Medicine, Sweden.
    Burkill, S.
    Clinical Epidemiology Division, Department of Medicine Solna, Sweden; Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Hiyoshi, Ayako
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Clinical Epidemiology and Biostatistics.
    Olsson, T.
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Bahmanyar, S.
    Clinical Epidemiology Division, Department of Medicine, Solna, Sweden; Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden .
    Wormser, D.
    F. Hoffmann-La Roche Ltd, Basel, Switzerland.
    Geissbuehler, Y.
    Novartis Pharma AG, Basel, Switzerland.
    Moore, A.
    Novartis Pharma AG, Basel, Switzerland.
    Kharat, V.
    Novartis Pharmaceuticals Corporation, East Hanover NJ, United States.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Clinical Epidemiology Division, Department of Medicine, Solna, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Burden of comorbid diseases among MS patients in Sweden2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 646-646Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: A raised risk for several comorbid diseases among MS patients has been identified. Most previous studies examined diseases separately rather than considering the overall burden of comorbidity. Multiple comorbidities may have important implica-tions for clinicians managing MS patients.

    Aims: To describe the lifetime burden of comorbid diseases among MS patients and the rate of these diseases compared with the general population in Sweden.

    Methods: MS patients identified using the MS Register and the Patient Register (PR) between 1964-2012 (n=25476) were matched by sex, age and county of residence with up to 10 general population comparators (n=251170). Prevalent and incident diag-noses of diseases other than MS for seven diseases categories were identified using the PR between 1987-2012. The total num-ber of comorbid diseases were compared using chi-square tests and prevalence rate ratios (PRR) were calculated. Hazard ratios (HR) were estimated using Cox regression and flexible non-para-metric survival models with age as the underlying time scale, MS as exposure, an additional comorbid disease as the outcome, adjusted for matching variables, education, number of previous comorbid diseases, and duration since study entry.

    Results: The proportion of MS patients with 1,2 or 3+ comorbid disease diagnoses was greater than in the comparison cohort across all age groups (p< 0.001). The largest PRR (range 1.22-9.99) were among younger age groups (6-18,19-40,41-60 years) in autoim-mune, cardiovascular, diabetes and seizure disease categories. Additionally, PRR were elevated in depression and respiratory dis-eases, but not for renal diseases. PRR between 61-80 and 81-100 years were reduced compared to younger groups across all comorbid diseases, but remained elevated for respiratory, seizure and renal dis-eases. The adjusted HR for an additional diagnosis in MS patients was 1.7 (95% CI 1.66-1.75). Flexible modelling showed signifi-cantly higher risk for all ages of an additional disease diagnosis in MS patients; twice the risk (95% CI 1.8-2.2) up to age 35 years and decreasing with age to 1.3 (95% CI 1.5-1.25) over age 80 years.

    Conclusions: MS patients in Sweden experience an increased burden of comorbidity and tend to be diagnosed with these dis-eases at an earlier age than the general population. This increased disease burden demonstrates the clinical reality of treating MS, indicating the need for integrated treatment approaches over sev-eral medical specialties.

  • 32.
    Vattulainen, P.
    et al.
    StatFinn and EPID Research (an IQVIA Company), Espoo, Finland.
    Burkill, S.
    Karolinska Institute, Stockholm, Sweden.
    Geissbuehler, Y.
    Novartis Pharma AG, Basel, Switzerland.
    Sabido, M.
    Merck KGaA, Darmstadt, Germany.
    Popescu, C.
    Biogen Ltd, Maidenhead, United Kingdom.
    Suzart-Woischnik, K.
    Bayer AG, Berlin, Germany.
    Myhr, K. -M
    Department of Neurology, Haukeland University Hospital, Bergen, Norway.
    Montgomery, Scott
    Örebro universitet, Institutionen för medicinska vetenskaper. Karolinska Institute, Stockholm, Sweden; University College London, London, United Kingdom.
    Korhonen, P.
    StatFinn and EPID Research (an IQVIA Company), Espoo, Finland.
    Prevalence of infant outcomes at birth after exposure to interferon beta prior to or during pregnancy: a register-based cohort study in Finland and Sweden among women with MS2019Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 619-619Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Women with multiple sclerosis (MS) are often diagnosed and treated at childbearing age. Systematic reviews and registry studies suggest that MS and interferon-beta (IFNβ) expo-sure might affect birth weight and head circumference.

    Objectives: To determine the prevalence of categorical measures of birth weight for gestational age (small for gestational age (SGA), large for gestational age (LGA)), low birth weight, and low head circumference in IFNβ exposed and unexposed pregnant women with MS from health registers in Finland and Sweden.

    Methods: In this cohort study, health register data from Finland (1996-2014) and Sweden (2005-2014) were used to study women with MS 1) dispensed only IFNβ within 6 months prior to date of last menstrual period or during pregnancy (IFNβ-exposed) and 2) without any dispensed MS disease modifying drugs (MSDMDs) (unexposed). The prevalence, with 95% confidence interval (CI), of the following birth outcomes was described for the IFNβ-exposed and the unexposed: SGA, LGA, low birth weight for live births, and low head circumference for infants with full term live birth (at least 37 gestational weeks). For SGA, LGA, and head circumference, national gestational age and sex-specific national references were used. No adjustments for potential confounding factors were performed.

    Results: Among 666 IFNβ-exposed and 1330 unexposed live births, the prevalence of the infant outcomes were similar between the IFNβ-exposed vs the unexposed. Comparing the exposed vs unexposed, SGA was 2.1% (95%CI 1.2-3.5) vs 2.0% (95%CI 1.3-2.9), and LGA 0.8% (95%CI 0.2-1.7) vs 0.8% (95%CI 0.4-1.5).The prevalence of low birth weight was 3.9% (95%CI 2.6-5.7) among IFNβ-exposed and 4.8% (95%CI 3.7-6.1) among the unexposed live births. Among 619 IFNβ-exposed and 1219 unexposed full term live births, the prevalence of low head circumfer-ence was 1.9% (95%CI 1.0-3.4) among the IFNβ-exposed vs 1.1% (95%CI 0.6-1.8) among the unexposed births.

    Conclusions: The data from Finnish and Swedish health registers showed no evidence that IFNβ exposure before and during pregnancy affected infant birth weight and head circumference.

  • 33.
    Wittrin, A.
    et al.
    Örebro Univ Hosp, Örebro, Sweden.
    Nilsagård, Ylva
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Westerdahl, Elisabeth
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Gunnarsson, Martin
    Örebro universitet, Institutionen för läkarutbildning. Örebro Univ Hosp, Örebro, Sweden.
    Self-assessment of walking ability in patients with multiple sclerosis and its impact on the expanded disability status scale (EDSS) score2013Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, nr 11, s. 118-118Artikel i tidskrift (Övrigt vetenskapligt)
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