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Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study
Author(s) -
Shirani A.,
Zhao Y.,
Karim M. E.,
Petkau J.,
Gustafson P.,
Evans C.,
Kingwell E.,
Kop M. L.,
Oger J.,
Tremlett H.
Publication year - 2014
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12324
Subject(s) - medicine , multiple sclerosis , hazard ratio , observational study , interferon beta , proportional hazards model , interferon beta 1a , beta (programming language) , oncology , confidence interval , immunology , computer science , programming language
Background and purpose It was recently reported that there was no significant overall association between interferon beta exposure and disability progression in relapsing−remitting multiple sclerosis ( RRMS ) patients in an observational study from C anada. In the current study, the potential for heterogeneity in the association between exposure to interferon beta and disability progression across patients' baseline characteristics was investigated. Methods RRMS patients treated with interferon beta ( n = 868) and two cohorts of untreated patients (829 contemporary and 959 historical controls) were included. The main outcome was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained E xpanded D isability S tatus S cale ( EDSS ) score 6 using a multivariable C ox model, with treatment as a time‐varying predictor, testing interaction effects for five pre‐specified baseline characteristics: sex, age, disease duration, EDSS and annualized relapse rate ( ARR ) based on the previous 2 years. Results Significant heterogeneity was found in the association of interferon beta exposure and disability progression only across ARR , and only when treated patients were compared with historical controls ( P = 0.005 at a B onferroni‐adjusted alpha of 0.01). For patients with ARR >1, treatment‐exposed time was associated with a hazard ratio of 0.38 (95% CI 0.20–0.75) for disability progression compared with the unexposed time. Conclusions RRMS patients with more frequent relapses at baseline may be more likely to benefit from interferon beta treatment with respect to long‐term disability progression.