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.

• Authors: Peter C Taylor, Emilia Quattrocchi, Stephen Mallett, Regina Kurrasch, Jørgen Petersen, David J Chang
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 70 Issue 12 Pg. 2119-25 (Dec 2011) ISSN: 1468-2060 [Electronic] England
• PMID: 21859685 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD20
• Antirheumatic Agents
• Biomarkers
• C-Reactive Protein
• ofatumumab
• Methotrexate

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antigens, CD20 (immunology)
• Antirheumatic Agents (administration & dosage, adverse effects, therapeutic use)
• Arthritis, Rheumatoid (drug therapy)
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Double-Blind Method
• Drug Eruptions (etiology)
• Drug Therapy, Combination
• Female
• Humans
• Infusions, Intravenous
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Quality of Life
• Severity of Illness Index
• Treatment Outcome