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.