Genovese MC et al. (2008) Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis. A phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum 58: 2652–2661

The results from the first human trial of ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of rheumatoid arthritis (RA) have recently been presented. Genovese et al. investigated the safety and efficacy of ocrelizumab in 237 patients with active, moderate to severe RA who had shown an inadequate response to therapy with ≤6 DMARDs. Patients were receiving concomitant methotrexate, and were randomly allocated to receive two infusions of 10, 50, 200, 500 or 1,000 mg ocrelizumab or placebo.

A robust clinical response was seen across all dosages, with greater benefits in those receiving doses ≥200 mg. Rapid B-cell depletion was observed after the first infusion across all treatment groups, with a trend towards earlier B-cell recovery in those receiving 10 or 50 mg ocrelizumab. Reductions in C-reactive protein levels were greatest in the high-dose groups. Doses of 200 mg or higher had very low immunogenicity compared with the lower doses. Serious adverse events occurred in 17.9% of ocrelizumab-treated patients and 14.6% of the placebo group. Rates of serious infection were similar in both groups (2.0% versus 4.9%). Rates of infusion were similar across all treatment groups, and were higher than the rates in the placebo group (51% versus 17%).

These results suggest that ocrelizumab, at doses of 200 mg and over, combined with methotrexate could be an effective therapeutic strategy for patients with treatment-refractory RA.