No Go for MS Combination Therapy

NEW ORLEANS—Hopes that two MS drugs would team up to deliver an especially powerful punch have fizzled, based on results presented at the annual meeting of the American Academy of Neurology in New Orleans. Glatiramer acetate (Copaxone) and interferon β-1a (Avonex) together reduce the risk of relapse in MS no more than each individual drug on its own, researchers reported on Friday, April 27.

The multicenter, double-blinded, randomized clinical trial, called CombiRX, is the largest and longest-running longitudinal study of combination therapies for MS: It followed 1008 patients for at least 3 years and aimed to determine whether two effective drugs might boost each other’s power when combined. The study began enrolling patients in 2005, and because it concluded only after the last-recruited patient completed the set timeframe, some participants were followed for as long as 7 years. Eighty-one percent of subjects remained in the study for the full 3 years. In its three-arm design, patients received glatiramer acetate plus placebo, interferon β-1a plus placebo, or both meds. The study was funded by the U.S. National Institute of Neurological Disorders and Stroke, with drugs donated by Biogen Idec and Teva.

According to the much-awaited trial data, patients taking glatiramer acetate had an annualized relapse rate (ARR) of 0.11, those on interferon β-1a had an ARR of 0.16, and those on both drugs had an ARR of 0.12, reported Fred Lubin, a neurologist at Mount Sinai Medical Center in New York City and the study’s lead investigator. The difference between combination therapy and either drug alone was not statistically significant. Copaxone by itself, however, showed a statistically significant 5% reduction in relapse rate compared to Avonex by itself.

Neuroimaging data from the trial reported at the meeting earlier in the week by Jerry Wolinsky of the University of Texas Health Science Center in Houston showed an improvement for the combination therapy on new lesion activity and total lesion volume. However, taking both drugs seemed to provide no benefit for other measures that can be assessed radiologically, such as brain atrophy. Because some of the MRI results did favor the combination therapy, the researchers plan to look closely at whether these radiological differences are most apparent in the longest enrolled patients. Such a result might suggest that benefits of the combination treatment could pull ahead of the single drugs if administered for longer periods of time.

The results are disappointing, considering the outlay of time and money involved, says Bruce Cree, a neurologist at the University of California, San Francisco. One silver lining of the study’s negative finding, however, is that researchers collected extensive biomarker data on many of its participants. Mining that information might provide clues about how to predict which of the treatments will work best for individual patients. “Of course, we look forward to seeing any biomarker data that would help us determine who is going to respond to these drugs,” Cree says. Overall, however, Cree says that the field is moving beyond the two agents tested in CombiRx, because newer therapeutics seem to be more effective.

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Thumbnail image on landing page. "New Orleans, Louisiana, USA." Nighttime view of multi-story building with decorative iron galleries, Royal Street at St. Peter, French Quarter. Copyright, 2004, Falkue. Released under the GNU Free Documentation License.