An investigational anti-B-cell activating factor (BAFF) monoclonal antibody is no better than placebo in achieving clinical response in patients with rheumatoid arthritis (RA) who had not responded to methotrexate (MTX), a phase III study has shown.

There was no difference in ACR20 (American College of Cardiology 20 percent) response score at week 24 – the primary endpoint of the study – or change in mTSS (modified Total Sharp Score) from baseline at week 52 between patients treated with tabalumab and placebo. Nearly 30 percent of patients treated with tabalumab 120 mg every 4 weeks and 32.8 percent of those assigned to tabalumab 90 mg every 2 weeks achieved ACR20 compared with 25.1 percent for placebo. There were also no significant differences between the tabalumab and placebo groups in the percentage of patients achieving ACR50 and ACR70 responses at the end of treatment. [Ann Rheum Dis 2015; doi:10.1136/annrheumdis-2014-207090]

“Despite changes in CD20+ B cells, RF rheumatoid factor, and immunoglobulins following tabalumab treatment, BAFF inhibition with tabalumab was not clinically, functionally, or structurally efficacious in patients with moderate-to-severe RA taking MTX,” said lead investigator Professor Josef Smolen of the Medical University of Vienna in Vienna, Austria.

The study included 1,041 patients with moderate-to-severe RA (≥6 months duration) who had inadequate responses to MTX therapy, randomized to tabalumab 120 mg every 4 weeks or 90 mg every 2 weeks or placebo. Median CD20+ B-cell counts increased at week 1 in the tabalumab groups, but decreased from week 4 to 52. The differences in absolute and relative CD20+ B-cell-level changes from baseline to week 52 were significant in both tabalumab groups compared with the placebo group (p<0.001). Numerically more serious infections were seen with tabalumab groups (1.7 and 0.6 percent vs 0.3 percent for placebo).

The study was terminated early due to insufficient efficacy.

“BAFF blockade alone does not appear to provide sufficient interference with the immunopathogenesis of RA,” said the researchers.

Tabalumab is the third anti-BAFF monoclonal antibody to fail in RA studies. Earlier, belimumab and atacicept also failed to achieve significant responses in RA patients on background MTX.