Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis

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Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis

TitleAssociation between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis
Publication TypeJournal Article
Year of Publication2012
AuthorsShirani, A, Zhao, Y, Karim, ME, Evans, C, Kingwell, E, van der Kop, ML, Oger, J, Gustafson, P, Petkau, J, Tremlett, H
JournalJournal of the American Medical Association
Volume308
Pagination247-256
Date PublishedJUL 18
Type of ArticleArticle
ISSN0098-7484
Abstract

Context Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. Objective To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Design, Setting, and Patients Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n=868) were compared with untreated contemporary (n=829) and historical (n=959) cohorts. Main Outcome Measures The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. Results The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P=.14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P=.07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Conclusion Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability. JAMA. 2012;308(3):247-256 www.jama.com

DOI10.1001/jama.2012.7625