Long-Term Study Determines Early Predictors of Response to Interferon Beta-1a in Patients With MS

In patients with relapsing-remitting multiple sclerosis (MS), progression of disability and higher relapse rates are early markers of long-term disease severity, while initiation of treatment with intramuscular interferon (IFN) beta-1a can delay this progression when initiated in patients with low disease burden, new findings suggest.

Richard Rudick, MD, director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic Foundation, in Ohio, presented the results here at the Consortium of Multiple Sclerosis Centers (CMSC) 23rd Annual Meeting in a poster session.

Previous data from the National Institutes of Health–funded Multiple Sclerosis Collaborative Research Group (MSCRG) indicated that intramuscular IFN beta-1a decreased relapse frequency and slowed disability over 2 years, the researchers note. The current study assessed data from a 15-year follow-up of that study to identify early markers of long-term response to therapy in the MSCRG study population.

A strong relationship between magnetic resonance imaging (MRI) activity during the first 2 years of the MSCRG study and long-term Expanded Disability Status Scale (EDSS) progression at 15 years was evident in patients who received intramuscular IFN beta-1a, but this association was not observed with patients who received placebo.

Specifically, 87.5% of IFN-beta-1a–treated patients who had 2 or more gadolinium-enhanced lesions at 2 years progressed to EDSS scores of 6.0 or greater at 15 years compared with only 35.3% of IFN-treated patients with fewer than 2 lesions (P = .0003).

In addition, 61.5% of IFN-treated patients who had at least 3 new or enlarging T2 lesions at year 2 progressed to EDSS scores 6.0 or greater at 15 years, whereas only 38.1% of patients with less than 3 new or enlarging T2 lesions reached that disability level at year 15.

"We previously reported that IFN beta-1a recipients who developed 3 or more new T2 lesions during 2 years had greater disability progression and more brain atrophy compared with IFN recipients with less MRI activity," Dr. Rudick told Medscape Neurology. "We did not see this same relationship in the placebo recipients. The current study confirmed those results but with much longer follow-up and using clear-cut markers of clinically significant disability," he said.

According to Dr. Rudick, the findings have clinical implications in that they suggest that MRI may provide a method to identify patients who respond poorly to IFN beta-1a. "This would have major implications, because patients could be continued on IFN beta-1a if their MRI is stable and switched to other treatments if it is not," he said. "It also would provide a possible outcome measure (MRI change while on IFN beta-1a) to develop biological markers of treatment response," he added.

Further Support

According to Mark S. Freedman, MD, professor of neurology at the University of Ottawa, in Ontario, and director of the Multiple Sclerosis Research Clinic, the findings from this study support evidence from other studies showing that early activity in patients receiving treatment is an indicator of poor prognosis.

However, he points out that about half of the patients in the initial study did not continue on to the 15-year follow-up phase, making it difficult to make conclusions regarding the long-term efficacy as it relates to early response.

"I am an advocate of treating clinically isolated syndrome (CIS), or the first event of MS," Dr. Freedman told Medscape Neurology. "For patients who clearly have CIS, all current treatments are likely to translate into better long-term protection," he said, although he added that not all agents should be used for initial treatment.

"We have now several treatments and are soon to have several more choices," he added.