NEW ORLEANS—A combination of interferon beta-1a and glatiramer acetate was not significantly better than glatiramer acetate alone at reducing the annualized relapse rate over three years in patients with relapsing-remitting multiple sclerosis (MS), researchers reported at the 64th Annual Meeting of the American Academy of Neurology. Glatiramer acetate reduced the annual relapse rate significantly more than interferon beta-1a did.
The percentage of patients relapsing over 36 months did not differ significantly between patients receiving interferon beta-1a, patients receiving glatiramer acetate, and those receiving a combination of the two drugs, said Fred Lublin, MD, Saunders Family Professor of Neurology at Mount Sinai School of Medicine in New York City. The time to first relapse did not differ between the three groups, and the percentage with six-month confirmed Expanded Disability Status Scale (EDSS) progression was also similar in all three groups.
The CombiRx Trial
These results were drawn from the CombiRx trial, a multicenter, double-blind, randomized study that Dr. Lublin and his colleagues conducted to determine whether interferon beta-1a and glatiramer acetate in combination were more effective than either drug alone in treating relapsing-remitting MS. The study’s primary end point was the annualized relapse rate over three years. The researchers enrolled 1,008 patients with relapsing-remitting MS at 68 clinical sites between January 2008 and April 2009.
Half the participants were randomized to receive interferon beta-1a and glatiramer acetate. One quarter of patients received interferon beta-1a and placebo, and 25% received glatiramer acetate and placebo. The study lasted for 36 months, and, during a blinded extension, participants stayed on their assigned treatment until the last patient had completed 36 months of therapy.
Eligible patients were ages 18 to 60, had not used either of the two drugs previously, and had an EDSS score of 5.5 or less. Approximately 81% of patients completed the 36-month trial. “This is a very good retention rate for an MS study,” said Dr. Lublin. “The usual MS phase 3 trial reports on 24-month information.”
Drug Combination Reduces T2 Lesions More Than Either Agent Alone
When the researchers examined the percentage of patients who had no relapse activity and no confirmed change in EDSS, they saw no difference between the three treatment groups. “However, when you go to a full definition of disease-activity–free status—meaning no relapse activity, no progression on EDSS, no new T2 lesions, and no new gadolinium-enhancing lesions—the combination group is significantly better than either of the two treatment groups,” observed Dr. Lublin.
Patients who entered the study with an EDSS score of 0 had a ninefold greater risk of confirmed disease progression than patients with an EDSS score higher than 0. “We’ve not seen this sort of data before, and we’re studying it now to see what was driving those changes,” said Dr. Lublin. The researchers will analyze the longer-term extension phase of the CombiRx study to examine if the differences between patient groups observed by MRI will predict later clinical differences.
—Erik Greb