Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial

OBJECTIVES: To evaluate the efficacy and safety of intravenous ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, active rheumatoid arthritis (RA) patients despite methotrexate treatment. METHODS: In this double-blind, placebo-controlled, phase III study, active RA patients on stable methotrexate were randomly assigned to one course of two infusions of ofatumumab 700 mg (n=130) or placebo (n=130), 2 weeks apart. The primary endpoint was the ACR20 response at week 24. Secondary endpoints included ACR50/70, EULAR response, disease activity score based on 28 joints using C-reactive protein, adverse events (AE) and immunogenicity. RESULTS: At week 24, a greater proportion of patients on ofatumumab compared with placebo achieved an ACR20 response (50% vs 27%, p<0.001) and a good or moderate EULAR response (67% vs 41%, p<0.001). All other key secondary efficacy endpoints were significantly improved on ofatumumab. Efficacy observed by 8 weeks was sustained throughout the study. The most common AE for ofatumumab versus placebo were rash (21% vs <1%) and urticaria (12% vs <1%), mostly occurring on the first infusion day. Overall, first-dose infusion reactions were 68% for ofatumumab and 6% for placebo, mostly mild to moderate; second-dose infusion reactions markedly declined (<1% and 0%). Serious AE were reported in 5% of ofatumumab versus 3% of placebo patients. Infection rates were 32% and 26% (serious infections <1% and 2%), respectively. One death (interstitial lung disease), unrelated to study drug, was reported on ofatumumab. No antidrug antibodies were detected in ofatumumab patients. CONCLUSIONS: Ofatumumab significantly improved all clinical outcomes in biological-naive, active RA patients with no detectable immunogenicity at week 24. No unexpected safety findings were identified. TRIAL REGISTRY: clinical trials.gov registration number NCT00611455