Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study
Version of Record online: 18 DEC 2013
© 2013 The Author(s) European Journal of Neurology © 2013 EAN
European Journal of Neurology
Volume 21, Issue 6, pages 835–844, June 2014
How to Cite
Shirani, A., Zhao, Y., Karim, M. E., Petkau, J., Gustafson, P., Evans, C., Kingwell, E., van der Kop, M. L., Oger, J. and Tremlett, H. (2014), Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study. European Journal of Neurology, 21: 835–844. doi: 10.1111/ene.12324
- Issue online: 8 MAY 2014
- Version of Record online: 18 DEC 2013
- Manuscript Accepted: 29 OCT 2013
- Manuscript Received: 8 JUL 2013
- Natural Sciences and Engineering Research Council of Canada
- Canadian Institutes of Health Research. Grant Number: MOP-93646
- Christopher Foundation
- University of British Columbia
- National Multiple Sclerosis Society. Grant Number: RG 4202
- British Columbia;
- disability progression;
- interferon beta;
- multiple sclerosis;
- observational studies
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 Canada. 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.
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 Expanded Disability Status Scale (EDSS) score 6 using a multivariable Cox 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.
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 Bonferroni-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.
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.