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Gunnarsson, Martin
Publikasjoner (10 av 30) Visa alla publikasjoner
Granqvist, M., Burman, J., Gunnarsson, M., Lycke, J., Nilsson, P., Olsson, T., . . . Piehl, F. (2019). Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS. Multiple Sclerosis, Article ID 1352458519866600.
Åpne denne publikasjonen i ny fane eller vindu >>Comparative effectiveness of dimethyl fumarate as the initial and secondary treatment for MS
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2019 (engelsk)Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, artikkel-id 1352458519866600Artikkel i tidsskrift (Fagfellevurdert) Epub ahead of print
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.

sted, utgiver, år, opplag, sider
Sage Publications, 2019
Emneord
Multiple sclerosis, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-beta, relapsing-remitting
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-75814 (URN)10.1177/1352458519866600 (DOI)000480888300001 ()31392923 (PubMedID)
Merknad

Funding Agency:

Neuroförbundet, Stockholms Läns Landsting and Vetenskapsrådet 

Tilgjengelig fra: 2019-08-23 Laget: 2019-08-23 Sist oppdatert: 2019-08-29bibliografisk kontrollert
de Flon, P., Laurell, K., Sundström, P., Blennow, K., Söderström, L., Zetterberg, H., . . . Svenningsson, A. (2019). Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial. Acta Neurologica Scandinavica, 139(5), 462-468
Åpne denne publikasjonen i ny fane eller vindu >>Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial
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2019 (engelsk)Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, nr 5, s. 462-468Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVE: The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.

MATERIALS & METHODS: Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed for two years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed for an additional three years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.

RESULTS: The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 (SD 393) to 354 (SD 174) pg/mL; p=0.006) and was statistically significant. The corresponding reduction in plasma-NFL was 18% (from 9.73 (SD 7.04) to 7.94 (SD 3.10) pg/mL; p=0.055) and did not reach statistical significance.

CONCLUSION: This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimise the use in clinical trials.

sted, utgiver, år, opplag, sider
John Wiley & Sons, 2019
Emneord
Multiple sclerosis, cerebrospinal fluid, clinical trial, neurofilament light, plasma, rituximab, treatment
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-72477 (URN)10.1111/ane.13078 (DOI)000464338600008 ()30740668 (PubMedID)2-s2.0-85062548724 (Scopus ID)
Merknad

Funding Agencies:

County Council of Västerbotten  

County Council of Jämtland/Härjedalen  

County Council of Örebro  

Unit of Research, Education and Development, Region Jämtland Härjedalen  JLL-379731  JLL-649011  JLL 467731 

Syskonen Perssons Donationsfond  JLL-467381  JLL-652541 

Tilgjengelig fra: 2019-02-14 Laget: 2019-02-14 Sist oppdatert: 2019-06-18bibliografisk kontrollert
Bridel, C., Gunnarsson, M. & Weiss, E. J. (2019). Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis. JAMA Neurology, 76(9), 1035-1048
Åpne denne publikasjonen i ny fane eller vindu >>Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis
2019 (engelsk)Inngår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 76, nr 9, s. 1035-1048Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

Key Points: QuestionHow do levels of neurofilament light in cerebrospinal fluid (cNfL) compare between neurological conditions and with healthy controls?

Findings: Among 10 059 individuals in this systematic review and meta-analysis, cNfL was elevated in most neurological conditions compared with healthy controls, and the magnitude of the increase varies extensively. Although cNfL overlaps between most clinically similar conditions, its distribution did not overlap in frontotemporal dementia and other dementias or in Parkinson disease and atypical parkinsonian syndromes.

Meaning: The cNfL is a marker of neuronal damage and may be useful to differentiate some clinically similar conditions, such as frontotemporal dementia from Alzheimer disease and Parkinson disease from atypical parkinsonian syndromes.

This systematic review and meta-analysis assesses the associations of age, sex, and diagnosis with neurofilament light in cerebrospinal fluid and evaluates its potential in discriminating clinically similar conditions.

Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.

Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.

Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.

Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.

Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.

Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses.

Results: Data were collected for 10059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n=2795), dementias and predementia stages (n=4284), parkinsonian disorders (n=984), and HC (n=1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.

Conclusions and Relevance: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

sted, utgiver, år, opplag, sider
American Medical Association, 2019
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-77243 (URN)10.1001/jamaneurol.2019.1534 (DOI)000486895500008 ()31206160 (PubMedID)2-s2.0-85067362736 (Scopus ID)
Tilgjengelig fra: 2019-10-14 Laget: 2019-10-14 Sist oppdatert: 2019-10-14bibliografisk kontrollert
Kågström, S., Fält, A., Forsberg, L., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2019). 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). Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 763-764
Åpne denne publikasjonen i ny fane eller vindu >>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)
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2019 (engelsk)Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 763-764Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
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.

sted, utgiver, år, opplag, sider
Sage Publications, 2019
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-77234 (URN)000485303103183 ()
Konferanse
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Forskningsfinansiär
Swedish Research CouncilThe Swedish Brain Foundation
Tilgjengelig fra: 2019-10-16 Laget: 2019-10-16 Sist oppdatert: 2019-10-16bibliografisk kontrollert
Luna, G., Alping, P., Burman, J., Fink, K., Fogdell-Hahn, A., Gunnarsson, M., . . . Frisell, T. (2019). Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurology
Åpne denne publikasjonen i ny fane eller vindu >>Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies
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2019 (engelsk)Inngår i: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157Artikkel i tidsskrift (Fagfellevurdert) Epub ahead of print
Abstract [en]

Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and glatiramer acetate (GA), the magnitude of potential risk increase is not well established in real-world populations. Even less is known about infection risk associated with rituximab, which is extensively used off-label to treat MS in Sweden.

Objective: To examine the risk of serious infections associated with disease-modifying treatments for MS.

Design, Setting, and Participants: This nationwide register-based cohort study was conducted in Sweden from January 1, 2011, to December 31, 2017. National registers with prospective data collection from the public health care system were used. All Swedish patients with relapsing-remitting MS whose data were recorded in the Swedish MS register as initiating treatment with rituximab, natalizumab, fingolimod, or interferon beta and GA and an age-matched and sex-matched general population comparator cohort were included.

Exposures: Treatment with rituximab, natalizumab, fingolimod, and interferon beta and GA.

Main Outcomes and Measures: Serious infections were defined as all infections resulting in hospitalization. Additional outcomes included outpatient treatment with antibiotic or herpes antiviral medications. Adjusted hazard ratios (HRs) were estimated in Cox regressions.

Results: A total of 6421 patients (3260 taking rituximab, 1588 taking natalizumab, 1535 taking fingolimod, and 2217 taking interferon beta/GA) were included, plus a comparator cohort of 42 645 individuals. Among 6421 patients with 8600 treatment episodes, the mean (SD) age at treatment start ranged from 35.0 (10.1) years to 40.4 (10.6) years; 6186 patients were female. The crude rate of infections was higher in patients with MS taking interferon beta and GA than the general population (incidence rate, 8.9 [95% CI, 6.4-12.1] vs 5.2 [95% CI, 4.8-5.5] per 1000 person-years), and higher still in patients taking fingolimod (incidence rate, 14.3 [95% CI, 10.8-18.5] per 1000 person-years), natalizumab (incidence rate, 11.4 [95% CI, 8.3-15.3] per 1000 person-years), and rituximab (incidence rate, 19.7 [95% CI, 16.4-23.5] per 1000 person-years). After confounder adjustment, the rate remained significantly higher for rituximab (HR, 1.70 [95% CI, 1.11-2.61]) but not fingolimod (HR, 1.30 [95% CI, 0.84-2.03]) or natalizumab (HR, 1.12 [95% CI, 0.71-1.77]) compared with interferon beta and GA. In contrast, use of herpes antiviral drugs during rituximab treatment was similar to that of interferon beta and GA and lower than that of natalizumab (HR, 1.82 [1.34-2.46]) and fingolimod (HR, 1.71 [95% CI, 1.27-2.32]).

Conclusions and Relevance: Patients with MS are at a generally increased risk of infections, and this differs by treatment. The rate of infections was lowest with interferon beta and GA; among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections. The different risk profiles should inform the risk-benefit assessments of these treatments.

sted, utgiver, år, opplag, sider
American Medical Association, 2019
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-77140 (URN)10.1001/jamaneurol.2019.3365 (DOI)31589278 (PubMedID)
Tilgjengelig fra: 2019-10-09 Laget: 2019-10-09 Sist oppdatert: 2019-10-09bibliografisk kontrollert
Biström, M., Hultdin, J., Andersen, O., Alonso-Magdalena, L., Jons, D., Gunnarsson, M., . . . Sundström, P. (2019). Leptin levels are associated with multiple sclerosis risk. Paper presented at 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019. Multiple Sclerosis, 25(Suppl. 2), 904-904
Åpne denne publikasjonen i ny fane eller vindu >>Leptin levels are associated with multiple sclerosis risk
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2019 (engelsk)Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, nr Suppl. 2, s. 904-904Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
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.

sted, utgiver, år, opplag, sider
Sage Publications, 2019
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-77235 (URN)000485303104016 ()
Konferanse
35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS 2019) / 24th Annual Conference of Rehabilitation in MS, Stockholm, Sweden, September 11-13, 2019
Forskningsfinansiär
Swedish Research Council, 2015-02419
Tilgjengelig fra: 2019-10-15 Laget: 2019-10-15 Sist oppdatert: 2019-10-15bibliografisk kontrollert
Alping, P., Piehl, F., Langer-Gould, A., Frisell, T., Burman, J., Fink, K., . . . Vrethem, M. (2019). Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations. Epidemiology, 30(2), 230-233
Åpne denne publikasjonen i ny fane eller vindu >>Validation of the Swedish Multiple Sclerosis Register Further Improving a Resource for Pharmacoepidemiologic Evaluations
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2019 (engelsk)Inngår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 30, nr 2, s. 230-233Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The Swedish Multiple Sclerosis Register is a national register monitoring treatment and clinical course for all Swedish multiple sclerosis (MS) patients, with high coverage and close integration with the clinic. Despite its great value for epidemiologic research, it has not previously been validated. In this brief report, we summarize a large validation of >3,000 patients in the register using clinical chart review in the context of the COMBAT-MS study. While further improving the data quality for a central cohort of patients available for future epidemiologic research, this study also allowed us to estimate the accuracy and completeness of the register data.

sted, utgiver, år, opplag, sider
Lippincott Williams & Wilkins, 2019
Emneord
Multiple sclerosis, Pharmacoepidemiology, Register, Validation
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-72870 (URN)10.1097/EDE.0000000000000948 (DOI)000458417200017 ()30721167 (PubMedID)2-s2.0-85061114400 (Scopus ID)
Merknad

Funding Agencies:

Patient-Centered Outcomes Research Institute (PCORI) Award  MS-1511-33196 

Swedish Foundation for MS Research  

Biogen  

Roche  

Biogen Idec  

Genzyme  

Novartis 

Tilgjengelig fra: 2019-03-01 Laget: 2019-03-01 Sist oppdatert: 2019-03-01bibliografisk kontrollert
Demirbüker, S. S., Kågström, S., Fält, A., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Berlin, Germany, October 10-12, 2018. Multiple Sclerosis, 24(Suppl. 2), 701-702
Åpne denne publikasjonen i ny fane eller vindu >>A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of dimethyl fumarate (IMSE 5)
Vise andre…
2018 (engelsk)Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 701-702Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
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.

sted, utgiver, år, opplag, sider
Sage Publications, 2018
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-70216 (URN)000446861401580 ()
Konferanse
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Berlin, Germany, October 10-12, 2018
Forskningsfinansiär
Swedish Research CouncilThe Swedish Brain Foundation
Merknad

Funding Agencies:

Biogen

Novartis  

Merck Serono  

Teva  

Sanofi Genzyme  

Genzyme

Tilgjengelig fra: 2018-11-20 Laget: 2018-11-20 Sist oppdatert: 2018-11-20bibliografisk kontrollert
Kågström, S., Fält, A., Demirbüker, S. S., Berglund, A., Hillert, J., Nilsson, P., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Berlin, Germany, October 10-12, 2018. Multiple Sclerosis, 24(Suppl. 2), 699-700
Åpne denne publikasjonen i ny fane eller vindu >>A Swedish nationwide pharmaco-epidemiological and genetic study of the long-term safety and effectiveness of natalizumab (IMSE 1)
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2018 (engelsk)Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 699-700Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
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.

sted, utgiver, år, opplag, sider
Sage Publications, 2018
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-70215 (URN)000446861401578 ()
Konferanse
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Berlin, Germany, October 10-12, 2018
Forskningsfinansiär
Swedish Research CouncilThe Swedish Brain Foundation
Merknad

Funding Agencies:

Biogen  

BiogenIdec  

Merck-Serono  

TEVA  

Sanofi-Genzyme  

Bayer-Schering  

Merck Serono  

Sanofi Genzyme  

Merck  

Roche 

Tilgjengelig fra: 2018-11-20 Laget: 2018-11-20 Sist oppdatert: 2018-11-20bibliografisk kontrollert
Fält, A., Kågström, S., Demirbuker, S. S., Hillert, J., Nilsson, P., Dahle, C., . . . Olsson, T. (2018). A Swedish nationwide pharmaco-epidemiological study of the long-term safety and effectiveness of alemtuzumab (IMSE 3). Paper presented at 34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Berlin, Germany, October 10-12, 2018. Multiple Sclerosis, 24(Suppl. 2), 706-707
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2018 (engelsk)Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 24, nr Suppl. 2, s. 706-707Artikkel i tidsskrift, Meeting abstract (Annet vitenskapelig) Published
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.

sted, utgiver, år, opplag, sider
Sage Publications, 2018
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-70217 (URN)000446861401586 ()
Konferanse
34th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Berlin, Germany, October 10-12, 2018
Forskningsfinansiär
Swedish Research CouncilThe Swedish Brain Foundation
Merknad

Funding Agencies:

Novartis  

BiogenIdec  

Merck-Serono  

TEVA  

Sanofi-Genzyme  

Bayer-Schering  

Merck Serono  

Sanofi Genzyme 

Tilgjengelig fra: 2018-11-20 Laget: 2018-11-20 Sist oppdatert: 2018-11-20bibliografisk kontrollert
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