October 26, 2007 (Prague, Czech Republic) — Results of a head-to-head clinical trial of glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) and interferon beta-1a (Rebif, Merck Serono) in patients with relapsing remitting multiple sclerosis (RRMS) found no significant difference in relapse rates in response to these treatments.
 

However, the trial, called the Rebif vs Glatiramer Acetate in Relapsing MS Disease (REGARD) trial, may have been underpowered to detect a statistically significant difference between groups, because relapse rates were much lower than expected.

The study was presented here at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis (ECTRIMS).

No Significant Difference

The REGARD trial was a randomized, assessor-blinded trial comparing interferon beta-1a and glatiramer acetate in relapsing-remitting multiple sclerosis. The trial enrolled a total of 764 patients who had been diagnosed with RRMS according to the 2001 McDonald criteria (1 or more clinical attacks in the previous 12 months, MRI evidence of brain lesions) and had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5.

Patients were randomly assigned to receive either 44-µg subcutaneous (sc) interferon beta-1a 3 times weekly (n = 386) or 20-mg sc glatiramer acetate once daily (n = 378) for 96 weeks. The primary end point was time to first relapse during 96 weeks of treatment.

An analysis of the results revealed no significant difference in the hazard rates (using a Cox proportional hazards model) for time to first relapse between the interferon-beta-1a and glatiramer-acetate groups (hazard ratio, 0.943; P = .643). A statistically significant difference, in favor of interferon beta-1a, was found only in a subgroup of patients with baseline median EDSS of 2 or less (n = 418; hazard ratio, 0.648; P = .022). There were no unexpected safety issues with either intervention.

The researchers also reported that the study population had much less active disease than those participating in previous RRMS trials. Only 258 out of 764 patients experienced 1 or more relapses during the course of the trial, whereas prior studies predicted that the number would be 460. Overall, the annualized relapse rate was 0.3. This is in contrast to a relapse rate of 0.87 for 44-µg interferon beta-1a in the Prevention of Relapses and Disability by Interferon Beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study.

Severely Underpowered

"The study did not meet the primary outcome, in that no difference was demonstrated regarding time to first relapse," lead investigator Daniel Mikol, MD, PhD, from the department of neurology at University of Michigan, in Ann Arbor, told Medscape Neurology & Neurosurgery. "However, the study was severely underpowered to show a difference at study end, as there were 45% fewer relapses than expected," Dr. Mikol noted. 

"The REGARD study underscores the challenges facing ongoing and future studies in relapsing-remitting MS, as patients being enrolled into such studies are 'less active' than previous study populations," Dr. Mikol went on to say. "This is probably due to the fact that there are a number of available therapeutic options, and competition for enrollment between clinical trials may also play a role," he explained.

"Given these factors, I feel that ongoing studies are at risk of being similarly underpowered if the predicted event rates are based on MS trials carried out 5 to 10 years ago, and additional studies may not meet their end points, unless the test agent is highly potent or an extremely high number of patients are enrolled," Dr. Mikol concluded.

This study was sponsored by Merck Serono SA. Dr. Mikol has worked as a paid consultant for Merck Serono SA.

23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis: Parallel session 9 (119). Presented October 14, 2007.