Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: results from a phase III multicentre, randomised, double-blind study.

Abstract

OBJECTIVES:

Randomised, double-blind, placebo-controlled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR).

METHODS:

1041 patients with moderate-severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks.

RESULTS:

There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were reported in the 90/Q2W group (2.3%, 4.3%, 2.3%).

CONCLUSIONS:

Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy.

TRIAL REGISTRATION NUMBER:

NCT01198002.

• Authors: Josef S Smolen, Michael E Weinblatt, Désirée van der Heijde, William F C Rigby, Ronald van Vollenhoven, Clifton O Bingham 3rd, Melissa Veenhuizen, Anne Gill, Fangyi Zhao, Wendy J Komocsar, Pierre-Yves Berclaz, Robert Ortmann, Chin Lee
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 8 Pg. 1567-70 (Aug 2015) ISSN: 1468-2060 [Electronic] England
• PMID: 25873635 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• B-Cell Activating Factor
• tabalumab
• Methotrexate

Topics

• Antibodies, Monoclonal (administration & dosage, pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (drug therapy)
• B-Cell Activating Factor (antagonists & inhibitors)
• Double-Blind Method
• Early Termination of Clinical Trials
• Humans
• Intention to Treat Analysis
• Methotrexate (therapeutic use)
• Treatment Failure