Author Affiliations: Departments of Neurology and Neurotherapeutics (Drs Greenberg, Stuve, and Frohman and Ms Frohman) and Ophthalmology (Dr Frohman), University of Texas Southwestern, Dallas; Department of Neurology, University of Pennsylvania, Philadelphia (Dr Balcer); Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland (Dr Calabresi); Department of Neurology, University of California, San Francisco (Dr Cree), and Department of Neurology, Stanford University, Stanford (Dr Steinman); Department of Neurology, Washington University, St Louis, Missouri (Dr Cross); Department of Neurology, University of Bochum, Bochum (Dr Gold), Department of Neurology, University of Munchen, Munich (Dr Hemmer), Department of Neurology, Heinrich Heine University, Dusseldorf (Dr Kieseier), and Department of Neurology, University of Muenster, Muenster (Dr Wiendl), Germany; Department of Neurology, Charles University, Prague, Czech Republic (Dr Havrdova); Department of Neurology, Wayne State University, Detroit, Michigan (Dr Lisak); Department of Neurology, Mount Sinai School of Medicine, New York, New York (Dr Miller); and Department of Neurology, The Ohio State University, Columbus (Dr Racke).
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.
Greenberg BM, Balcer L, Calabresi PA, Cree B, Cross A, Frohman T, Gold R, Havrdova E, Hemmer B, Kieseier BC, Lisak R, Miller A, Racke MK, Steinman L, Stuve O, Wiendl H, Frohman E. Interferon Beta Use and Disability Prevention in Relapsing-Remitting Multiple Sclerosis. JAMA Neurol. 2013;70(2):248-251. doi:10.1001/jamaneurol.2013.1017