According to the results of a multicentre, placebo-controlled trial (SCRIPT), a higher proportion of patients with rheumatoid arthritis (RA) who had failed to respond to at least one TNF inhibitor had an ACR20 response when treated with ocrelizumab, than with placebo.

The authors note that ocrelizumab is a humanised monoclonal antibody that selectively targets and depletes CD20+ B cells.  The purpose of the current study was to evaluate its safety and efficacy, when used in combination with methotrexate or leflunomide, in the treatment of patients with RA who had inadequate response to at least one anti-TNF agent.  A previous study has evaluated its use in patients failing to respond adequately to methotrexate (the STAGE study – see link below for NeLM summary).   

The study included adults with active RA of at least three months’ duration who had experienced an inadequate response (defined as toxicity or inadequate efficacy despite at least 3 months of treatment) to previous or current treatment with at least one TNF inhibitor, and who were receiving stable doses of methotrexate or leflunomide.  They were randomised to double-blind treatment with infusions of placebo (n=277), ocrelizumab 200mg (n=278), or ocrelizumab 500mg (n=285) on days 1 and 15 and then at weeks 24 and 26.  The co-primary endpoints were the proportion of patients with response according to the American College of Rheumatology 20% improvement criteria (ACR20) at weeks 24 and 48.

The main findings reported were as follows:

• At 24 weeks, ACR20 responses were seen in 22.0% of the placebo group, 42.2% of the ocrelizumab 200mg group, and 47.9% of the ocrelizumab 500mg group.  At 48 weeks, ACR20 responses were seen in 19.5%, 48.7%, and 50.7%, respectively (P<0.0001 versus placebo for each comparison at each time point).

• A greater proportion of patients in both ocrelizumab dose groups achieved ACR50 and ACR70 responses.  For example, the weighted differences in the proportions of ACR50 responders in the ocrelizumab 200mg and ocrelizumab 500mg groups versus placebo were 13.2% and 16.2%, respectively, at 24 weeks and 19.3% and 20.8%, respectively, at 48 weeks (P<0.0001 for each dose at each time point)

• The mean change in the modified Sharp/van der Heijde score (SHS; measures joint damage progression) was 1.00 in the ocrelizumab 500mg group and 2.58 in the placebo group (p=0.0017).  The difference between ocrelizumab 200mg and placebo was not statistically significant.

• Overall adverse events and infections were comparable in all treatment groups. Serious infections were observed more frequently in patients taking ocrelizumab (5.1% and 4.3%) than in those taking placebo (2.5%).

The authors conclude that both doses of ocrelizumab were clinically effective for improving signs and symptoms of RA in this difficult-to-treat population, and the high dose seemed to provide a statistically significant benefit with regards to the prevention of joint damage progression.  The rate of serious infections was however higher for both ocrelizumab doses as compared with placebo.