Despite the benefits of biologic agents and disease-modifying antirheumatic drugs (DMARDs), not all patients with rheumatoid arthritis (RA) have a positive response to treatment. The safety and efficacy of combination treatment of rituximab and methotrexate has been shown; the effect of rituximab dosage and glucocorticoids in the treatment of patients with RA, however, is not known.OBJECTIVE
The object of this study was to investigate the safety and efficacy of combination therapy, comprising methotrexate and rituximab with or without glucocorticoids, in patients with active RA who are refractory to treatment with DMARDs and biologic agents.DESIGN AND INTERVENTION
This was a 24-week, randomized, double-blind, placebo-controlled, dose-ranging phase IIb trial. In total, 465 patients with active RA were randomly allocated to one of nine treatment groups and received either rituximab 0.5 g (n=124), rituximab 1.0 g (n=192), or placebo (n=149). Patients also received either glucocorticoids, intravenous methylprednisolone premedication, or intravenous methylprednisolone premedication plus oral prednisone, for 2 weeks. All patients received 10-25 mg methotrexate per week; however, no other DMARDs were allowed. Treatment was administered on days 1 and 15.OUTCOME MEASURES
The primary outcome measure of this trial was an American College of Rheumatology (ACR) 20 response, indicated by 20% improvement. Secondary outcome measures were an ACR50 and an ACR70 response.RESULTS
More patients who received two 0.5 g or two 1.0 g infusions of rituximab met the ACR20 improvement criteria at week 24 (55% and 54%, respectively) than did patients who received placebo (28%; P<0.0001). ACR50 responses were achieved by 33%, 34%, and 13% of patients in these groups, respectively (P<0.001), and ACR70 responses were achieved by 13%, 20%, and 5% of patients, respectively (P<0.05). Changes in the Disease Activity Score in 28 joints (−1.79, −2.05, −0.67, respectively; P<0.0001) and moderate-to-good responses as assessed by the European League Against Rheumatism criteria (P<0.0001) reflected the ACR responses. Glucocorticoids did not contribute significantly to the primary efficacy endpoint. Intravenous glucocorticoid premedication reduced the frequency and intensity of first-infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Adverse effects were similar across the rituximab and placebo groups.CONCLUSION
The authors conclude that combination therapy with methotrexate and either dose of rituximab is a safe treatment option for patients with active RA.