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. Issue 8 (14th April 2015)

• Record Type: Journal Article
• Authors: Smolen, Josef S; Weinblatt, Michael E; van der Heijde, Désirée; Rigby, William F C; van Vollenhoven, Ronald; Bingham, Clifton O; Veenhuizen, Melissa; Gill, Anne; Zhao, Fangyi; Komocsar, Wendy J; Berclaz, Pierre-Yves; Ortmann, Robert; Lee, Chin
• Is Part Of: Annals of the rheumatic diseases. Volume 74:Issue 8(2015)
• Page Start: 1567
• Page End: 1570
• Publication Date: 2015-04-14
• Subjects: B cells -- Autoimmune Diseases -- Rheumatoid Arthritis; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-207090
• Languages: English
• ISSNs: 0003-4967

Abstract

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.