To test the hypothesis that a therapeutic dose of ocrelizumab (200 mg × 2), can be administered as a single-infusion (400 mg × 1) to achieve clinical efficacy and safety in patients with active rheumatoid arthritis.Patients & methods:
Three hundred and fourteen patients were randomized to double-blind placebo, ocrelizumab single-infusion or dual-infusion. The primary end point is American College of Rheumatology (ACR)20 response at week 24 for single-infusion ocrelizumab versus placebo.Results:
At 24 weeks, ACR20 responses for patients treated with single-infusion ocrelizumab were not statistically significantly superior to placebo (37.6% [95% CI: 28.8–46.4%] vs 28.1% [95% CI: 17.1–39.1%]; p = 0.2253). ACR20 for dual-infusion ocrelizumab was 52.7% (95% CI: 44.1–61.2%). Initial depletion of peripheral B cells appeared comparable after single and dual-infusions. However, subsequent B-cell repletion occurred earlier after single-infusion. Adverse events were comparable across groups.Conclusion:
Ocrelizumab 200 mg ×2 was efficacious, consistent with two other pivotal Phase III trials. The same drug amount administered as single-infusion was not significantly more efficacious than placebo and revealed differences in pharmacokinetic and pharmacodynamic profiles.