Interferon Beta and Disability in Patients with RRMS

Multiple sclerosis (MS), a chronic condition that usually affects people in the prime of their lives, is characterized by clinical progression over time manifested by the accumulation of disability.

The most widely prescribed disease-modifying medications approved by the FDA for the treatment of relapsing-remitting MS (RRMS) are interferon beta drugs. According to researchers, there is a lack of well-controlled longitudinal studies designed to assess the effect of interferon beta on the progression of disability in patients with RRMS.

Noting that drug efficacy is established through clinical trials conducted in optimal conditions, compared with drug effectiveness, which is measured in real-world settings, the researchers said, “The relationship between interferon beta exposure and disease progression is difficult to delineate based on clinical trials.”

Several postmarketing studies have shown the effectiveness of interferon beta as measured by relapses, disability, or magnetic resonance imaging. To examine the association between interferon beta exposure and disability progression in RRMS, the researchers conducted a retrospective cohort study based on prospectively collected data. They reported results of the study in the Journal of the American Medical Association [2012;308(3):247-256].

The data were collected from the British Columbia Multiple Sclerosis (BCMS) database. All patients with definite RRMS who registered with a BCMS clinic between April 1985 and December 2004, and who reached eligibility for interferon beta treatment during the same period, were included. There were 868 patients with RRMS treated with interferon beta who were compared with untreated contemporary (n=829) and historical (n=959) cohorts.

The primary outcome measure was time from eligibility for treatment with interferon beta to a confirmed and sustained score of 6 in the Expanded Disability Status Score (EDSS) confirmed at <150 days with no measurable improvement. A score of 6 (range of scores 0-10, with higher scores representing higher disability) on the EDSS is defined as requiring a cane to walk 100 meters.

Baseline characteristics among the 3 groups were similar, with some differences noted between the treated and control cohorts (the differences were considered clinically minor in most instances). Follow-up periods varied: 5.1 years for the treated cohort, 4.0 years for the untreated cohort (contemporary control), and 10.8 years for the historical control cohort.

When either the contemporary or historical control cohorts were considered, the adjusted Cox regression analysis using interferon beta exposure as a time-dependent covariate did not find strong evidence of an association of interferon beta exposure with the hazard of reaching an EDSS score of 6. However, the direction of the expected hazard ratios of reaching the outcome differed depending on which control cohort was included. When contemporary controls were considered, the HR was 1.30 (confidence interval [CI], 0.92-1.83; P=.14); when the historical controls were considered, the HR was 0.77 (95% CI, 0.58-1.02; P=.07).

The number of persons reaching the outcome was 94 (10.8%) in the treated cohort, 44 (5.3%) in the contemporary untreated cohort, and 222 (23.1%) in the historical untreated cohort. A higher EDSS score and older age at baseline were associated with a higher hazard of reaching an EDSS score of 6. Female sex and shorter duration of disease were associated with a lower (but not statistically significant) hazard of reaching the outcome.

Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results.

In conclusion, the researchers said, “Among patients with RMMS, administration of interferon beta was not associated with a reduction in progression of disability.”