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


METHODS
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.


METHODS
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.


CONCLUSIONS
Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.
Division of Neurology and Brain Research Centre, Department of Medicine and Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, Canada.
Afsaneh
A
Shirani
Yinshan
Y
Zhao
Mohammad Ehsanul
ME
Karim
Charity
C
Evans
Elaine
E
Kingwell
Mia L
ML
van der Kop
Joel
J
Oger
Paul
P
Gustafson
John
J
Petkau
Helen
H
Tremlett
D000328:Adult; D001955:British Columbia; D015331:Cohort Studies; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology*; D012189:Retrospective Studies; D055815:Young Adult
D007155:Immunologic Factors; D016899:Interferon-beta