Interferon beta not associated with less progression of disability in patients with RRMS

Journal of the American Medical Association (JAMA)Jul 18 2012

Among patients with relapsing-remitting multiple sclerosis (MS), treatment with the widely-prescribed drug to treat MS, interferon beta, was not associated with less progression of disability, according to a study in the July 18 issue of JAMA.

"A key feature of MS is clinical progression of the disease over time manifested by the accumulation of disability. Interferon beta drugs are the most widely prescribed disease-modifying drugs approved by the U.S. Food and Drug Administration for the treatment of relapsing-onset MS, the most common MS disease course," according to background information in the article. The authors add that there is a lack of well-controlled longitudinal studies investigating the effect of interferon beta on disability progression.

Afsaneh Shirani, M.D., of the University of British Columbia, Vancouver, Canada, and colleagues conducted a study to investigate the association between interferon beta exposure and disability progression in relapsing-remitting MS. The study included prospectively collected data (1985-2008) from British Columbia. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (prior to the approval of interferon beta) (n = 959) groups. The primary outcome measured was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 meters; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability).

Follow-up time (first to last EDSS measurement) differed between groups, being considerably longer for the historical untreated cohort (median [midpoint], 10.8 years), who by definition entered the study much earlier than the contemporary cohorts. The median follow-up times for the contemporary cohorts were 5.1 years for the treated group and 4.0 years for the untreated group.

The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8 percent in the treated group; 5.3 percent in the contemporary untreated group; and 23.1 percent in the historical untreated group.

"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 or the historical control cohort were considered," the researchers write. Further adjustment for co-existing illnesses and socioeconomic status, where possible, did not change interpretations.

"In conclusion, we did not find evidence that administration of interferon beta was associated with a reduction in disability progression in patients with relapsing-remitting MS. The ultimate goal of treatment for MS is to prevent or delay long-term disability. Our findings bring into question the routine use of interferon beta drugs to achieve this goal in MS. It is, however, possible that a subgroup of patients benefit from interferon beta treatment and that this association would not be discernable in our comprehensive 'real-world' study. Further work is needed to identify these potential patients; perhaps through pharmacogenomic or biomarker studies, paving the way for a tailored, personalized medicine approach. Our findings also encourage the investigation of novel therapeutics for MS."

Tobias Derfuss, M.D., and Ludwig Kappos, M.D., of University Hospital Basel, Switzerland, write in an accompanying editorial that the "rigorously collected data of Shirani and colleagues reinforce the conclusion that the associations between use of interferons and long-term disability, although plausible, remain unproven.

"As Shirani and colleagues suggest, more effective treatment options and better criteria that lead to more accurate selection of patients who might best respond to these treatments are needed. The relatively low progression rate in the untreated contemporary cohort is reassuring because it indicates that despite the unreliable explicit prognostic criteria, neurologists and patients in British Columbia seem to have made the right choices."