Oct 29, 2009
Results Published from Rituximab Study in Primary-Progressive MS
Primary Endpoint Not Reached but Subgroup Analysis Shows Evidence of Benefit in Younger Patients with Active Disease
A study of intravenous rituximab (Rituxan®, Genentech and Biogen Idec) in 439 people with primary-progressive MS has shown that the drug did not slow disease progression when compared with inactive placebo, the primary endpoint of the study. However, MRI scans suggested some benefit, and an analysis of subgroups within the study showed significant delays in patients younger than age 51 and with active disease observed on MRI scans. Early results from this OLYMPUS study were originally reported in a press release in 2008, and at the American Academy of Neurology Annual Meeting in 2009, and now Kathleen Hawker, MD (The Ohio State University Medical Center, Columbus) and colleagues have published their complete findings in Annals of Neurology (2009;66[4]:460-471)
Background: Rituximab binds to a molecule (CD20) on the surface of B cells and depletes them from the circulation for an average of 9 months. B cells are immune cells that make antibodies and may play a role in the immune attack on brain and spinal cord tissues in multiple sclerosis. Rituximab is approved for treating some forms of cancer. Researchers reported earlier this year that in a phase 2 study, one intravenous course of rituximab reduced disease activity and relapses for 48 weeks in people with relapsing-remitting MS (The New England Journal of Medicine 2008 Feb 14;358[7]:676-88). The current study evaluated the safety and effectiveness of rituximab in people with primary-progressive MS, a course of MS for which no specific treatments are currently on the market.
The Study: The study enrolled 439 subjects at 60 sites in the United States and Canada. Participants were age 18-65 years, had primary-progressive MS, and had had MS for at least one year. Patients were randomly assigned to receive either four intravenous doses of Rituxan or inactive placebo every six months for 96 weeks. Brain MRI scans were conducted before treatment, and at weeks 6, 48, 96 and 122. The primary outcome measured was the time to confirmed disease progression.
Rituximab did not reduce the time to disease progression, as compared with placebo. However, in a secondary endpoint, those on therapy had significantly less increase in brain lesion volume on MRI scans after 96 weeks. In addition, the study was designed to tease out effects in subgroups of patients. These further analyses showed that disease progression was significantly delayed in participants who were less than 51 years of age and in those whose pre-treatment MRIs showed signs of active (gadolinium-enhanced) brain lesions indicative of inflammation. This benefit was more pronounced in people younger than 51 with active brain lesions. The investigators conclude that these results will inform the design of future trials involving people with primary-progressive MS.
Serious adverse events occurred more often (16.1%) in the rituximab arm than in the placebo group (13.6%), with serious infections occurring more often in the rituximab group (4.5% vs. less than 1%) as well. There were more infusion-related reactions with rituximab, mostly mild to moderate in severity.
Comment: In an accompanying editorial, Hans-Peter Hartung, MD, and Orhan Aktas, MD (Heinrich-Heine-Universität Düsseldorf, Germany), comment: “The important and undoubtedly encouraging findings from the OLYMPUS trial presented here would suggest that PPMS anti-inflammatory and/or immunomodulatory therapy may be beneficial in younger patients with more rapid progression… Therefore further trials with rituximab or other CD20-directed monoclonal antibodies such as ocrelizumab or ofatumumab are definitely warranted in this particular patient population.” (A phase II study of ocrelizumab and a dose-finding study of ofatumumab are ongoing in people with relapsing-remitting MS, but not in primary-progressive MS. These trials are listed on clinicaltrials.gov.)
Read more about living with primary-progressive and other progressive courses of MS.
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