Is rituximab safe and effective in the treatment of rheumatoid arthritis (RA)?
TYPE OF REVIEW
This is a review of eight randomized controlled studies evaluating the risks and benefits of rituximab alone or in combination with any disease-modifying antirheumatic drug (DMARD) in the treatment of RA.
RELEVANCE FOR NURSING
RA is a chronic inflammatory condition in which the immune system attacks the lining of the joints, causing stiffness and pain. The aim of treatment is to halt progress toward permanent joint damage. First-line therapy for RA comprises traditional DMARDs, such as methotrexate. If patients are nonresponsive or experience intolerable adverse effects, newer DMARDs, known as biologic agents, may be used alone or in combination with traditional DMARDs. Rituximab is one such biologic agent; it eradicates B cells that produce harmful antibodies that damage joints. It is administered intravenously, and each course involves two 1,000-mg doses on days 0 and 15, typically at four-month intervals. Current evidence suggests that, when used in combination with methotrexate, rituximab is well tolerated and effective in the management of RA.
CHARACTERISTICS OF THE EVIDENCE
This review included eight randomized controlled studies involving 2,720 participants, mostly women. Their average age was 51 and all had moderate to severe RA of at least nine years’ duration. The studies reported on the efficacy or safety of rituximab alone or in combination with any DMARD (traditional or biologic) versus placebo or another DMARD. However, the review focused on the results of rituximab plus methotrexate since this combination is the most popular. The dosing schedule in all trials included one course of two iv injections of rituximab 1,000 mg on days 0 and 15, although five trials added an arm of two courses of rituximab 500 mg. Most trials evaluated the primary outcome measure at 24 weeks.
Rituximab plus methotrexate was statistically significantly more effective than methotrexate alone for the primary outcomes of improving RA symptoms and preventing disease progression. Fewer participants experienced serious adverse events when given rituximab with methotrexate than when given only methotrexate or a placebo. But, when compared with controls, patients treated with rituximab and methotrexate experienced increased adverse effects such as infusion reactions after first infusion, vascular events including hypertension, and coughs. The number of withdrawals due to adverse events was similar between groups; however, the total number of withdrawals—those due to adverse events plus those due to lack of efficacy—was greater in the control groups, supporting the beneficial effectiveness of rituximab.
BEST PRACTICE RECOMMENDATIONS
Rituximab plus methotrexate is an effective treatment for RA. Participants who were given rituximab plus methotrexate also reported significant improvements in their general health and well-being. The findings also appear to contradict suggestions that biologic drugs are more harmful to patients than conventional DMARDs.
There was no clear evidence to support the dosing regimen of two 1,000-mg doses of rituximab compared with two 500-mg doses in terms of treatment efficacy. Interestingly, results suggest that rituximab alone is more effective than methotrexate alone. However, long-term safety studies and comparative studies with other biologic drugs such as etanercept or infliximab are needed.
Lopez-Olivo M, et al. Rituximab for rheumatoid arthritis. Cochrane Database Syst Rev