Rituximab for relapsing-remitting multiple sclerosis

Background More than 80% of individuals with multiple sclerosis (MS) experience a relapsing-remitting disease course. Approximately ten years after disease onset, an estimated 50% of individuals with relapsing-remitting MS (RR-MS) convert to secondary progressive MS. Quality of life is considerably impaired in early RR-MS. The increased costs are associated with relapse occurrence and increasing disease severity. Pharmaceutical interventions aimed at delaying the progression of disease may help to reduce the economic burden of MS. It has been showed that B lymphocytes involve in the pathophysiology of MS and rituximab lyses B cells via complement and antibody-dependent cellular cytotoxicity. Current clinical trials are evaluating the role of rituximab as a B-cell-targeted therapy in the treatment of RR-MS. Objectives The effectiveness and safety of rituximab alone or as add-on, versus placebo or other treatments for RR-MS were assessed. Search methods The Trials Search Co-ordinator searched the Cochrane Multiple Sclerosis Group's Specialised Register (3 March 2011). We checked references in identified trials and manually searched the reports (2004 to May 2011) from neurological associations and MS Societies in Europe and America. We also communicated with researchers who were participating in trials on rituximab and contacted Genentech, BiogenIdec, Roche. Selection criteria All randomised double-blind controlled parallel clinical trials with a length of follow-up >= one year, evaluating rituximab, alone or as add-on with other therapies, versus placebo, or any other treatment for patients with RR-MS, without restrictions regarding dosage, administration frequency and duration of treatment. Titles and abstracts of the citations retrieved by the literature search were screened independently for inclusion/exclusion by two review authors. Any disagreement regarding inclusion was resolved by discussion, or by referral to a third assessor if necessary. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among review authors. Principal investigators of included studies were contacted for additional data or confirmation. Main results One trial involving 104 adult RR MS patients with an entry score <= 5.0 EDSS and at least one relapse during the preceding year was included. This trial evaluated rituximab alone versus placebo with a single course of rituximab (on day 1 and 15). Treated patients had a lower rate of relapse at 24 weeks but not at 48 weeks. The MRI data were available only at 24 weeks. A significant attrition bias was found at 48 week (40.0% in the placebo group and 15.9% in the rituximab group). Mild-to-moderate infusion-associated adverse events within 24 hours after the first rituximab infusion occurred in the rituximab group. Authors' conclusions We are unable to give any clear recommendations for the use of rituximab as a therapy for RR-MS. The beneficial effects of rituximab for RR-MS remain inconclusive because of the high attrition bias, the small number of participants and the short follow-up. However, short-term treatment with a single course of rituximab resulted to be safe for most patients with RR-MS. The potential benefits of rituximab for treating RR-MS need to be evaluated in large scale studies along with long-term safety. Disability progression and quality of life should be addressed in future research.