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

Abstract

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.

Conflict of interest statement

Competing interests Genmab and GlaxoSmithKline provided financial support to the institutions that participated in this study. PCT has received research grants from Merck, UCB, AstraZeneca, GlaxoSmithKline and Roche and has been an invited speaker and advisor for Abbott, Bristol-Myers Squibb, Centocor, Roche, Schering-Plough, Wyeth (acquired by Pfizer in October 2009), Genmab, GlaxoSmithKline and UCB. EQ, SM, RK and DJC are employees of GlaxoSmithKline and own stock in GlaxoSmithKline. JP was formerly employed at Genmab and owned Genmab stocks.

Figures

Figure 1

Disposition of patients up to week 24. *Patients could have more than one reason for screening failure. †One patient was randomly assigned to placebo but received ofatumumab. This patient is included in the placebo group for the intent-to-treat population, but in the ofatumumab group for the safety population.

Figure 2

ACR 20/50/70 responses at week 24 in patients receiving ofatumumab 700 mg or placebo. ACR20/50/70, 20%/50%/70% improvement as per American College of Rheumatology (ACR) criteria.

Figure 3

Mean change from baseline for DAS28 using CRP over time. CRP, C-reactive protein; DAS28, disease activity score based on 28 joints.