Long-Term Treatment Data Showcased in Interim Analysis of CARE-MS Extension and 7-Year CombiRx Results
Data from two important MS treatment trials, the CARE-MS extension study evaluating the monoclonal antibody Lemtrada (alemtuzumab) and CombiRx trial, comparing Copaxone (glatiramer acetate) + interferon beta-1a versus each treatment alone, were presented at the 2013 American Academy of Neurology (AAN) annual meeting in San Diego on March 16-23.
Interim Analysis of 3-year Data from CARE-MS Extension Study Shows Strong Long-Term Responses
Interim analysis of 3-year data from an extension of the two pivotal 2-year Phase 3 CARE-MS trials of Lemtrada (alemtuzumab) in patients with relapsing forms of MS was reported, showing that rates of relapse and sustained accumulation of disability remained low and levels of disability remained stable or improved through 3 years.1,2 The extension study included patients from both CARE-MS I, which was conducted in treatment-naive patients, and CARE-MS II, which was conducted in patients who had relapsed on prior treatment. Both original CARE-MS studies randomized patients to Lemtrada or interferon beta-1a, with the latter group allowed to cross-over to Lemtrada at 1 year. During the extension, patients were eligible to receive additional treatment with Lemtrada (given 12 mg IV once daily for 3 days) if there was evidence of disease activity.
Among patients who had been randomized to Lemtrada at the beginning of the original CARE-MS studies, 349 patients from CARE-MS I and 392 from CARE-MS II entered the extension phase. Over 80% of patients who received Lemtrada during the original studies did not require another dose at the beginning of the extension. After 1 year of the extension, annualized relapse rates were similar to those seen during the main studies. More than half of Lemtrada patients from each CARE-MS study were still relapse-free and over 80% free of sustained accumulation of disability after 1 year of the extension. Additionally, >70% of patients from each study had either improved or stable disability (measured by Expanded Disability Status Scale). In safety analysis, no new safety risks were identified, with rates of common and serious adverse events similar between the extension and main studies. The cumulative incidence of autoimmune thyroid disease was about 30% over the entire 3-year period, with rates similar between the extension and main studies.1,2
Seven-Year Results from CombiRx Extension Show Combination Treatment Not Superior to Copaxone Alone
Seven-year results from the extension phase of the CombiRx trial were reported and showed that the combination of Copaxone + interfereon beta-1a was not superior to Copaxone alone in patients with relapsing-remitting MS (RRMS).3-6 The CombiRx core study was a randomized, double-blind, placebo-controlled study comparing the combination of interferon beta-1a and Copaxone (glatiramer acetate) to each agent alone in patients with RRMS. A total of 1,008 patients were randomized in the CombiRx trial, which had a 3-year blinded follow-up period, the longest of any Phase 3 treatment study in MS. Almost 85% of randomized patients continued on after 3 years to participate in the extension phase. At 7 years, consistent with results for the blinded phase and previous extension updates, there were no significant differences between the combination treatment and Copaxone alone in terms of annualized rate of relapse (primary endpoint).5 Rates of relapse were very low over the entire course of 7 years for all three treatment arms (0.13 for interferon beta-1a; 0.09 for Copaxone; and 0.10 for Copaxone + interferon beta-1a), and significantly lower for both the combination and Copaxone arms versus interferon beta-1a. Even when a more stringent criteria were used to measure relapse, there continued to be no difference between the combined treatment group and Copaxone alone.6 Additionally, there were no significant differences in terms of rates of confirmed disability progression (using EDSS) between the combined treatment group and either agent alone.3 MRI results showed that each of the three treatment arms resulted in continued stabilization of both disease activity and brain volume loss from the first three years through 7 years.4,6 In the 3-year core study, there were differences in disease activity-free status driven mostly by MRI results (reductions in new lesion activity and total lesion volume) for the combined treatment versus either treatment alone. However, post hoc analysis of disease activity-free status suggested that while these differences remained at 7 years, they lessened over time and did not translate to clinical differences.6
Various explanations have been advanced for why the combination of Copaxone + interferon beta-1a fails to provide any advantage over Copaxone alone, including the possibilities that interferon beta-1a may neutralize the benefit of Copaxone or that both drugs exert their activity in the same patient subgroup.6,7 It may also be true that with continued follow-up, a difference in effect on the progression of long-term disability (an outcome that is best assessed over a longer period of time) may become apparent for the combination. Differences in MRI results for the combination treatment versus both single agents suggest that this may be a possibility6.