Tabalumab in rheumatoid arthritis patients with an inadequate response to methotrexate and naive to biologic therapy: a phase II, randomized, placebo-controlled trial

Abstract

Objective: Tabalumab, a fully human IgG4 monoclonal antibody, neutralizes soluble and membrane-bound BAFF. The aim of this study was to examine the tolerability and efficacy of tabalumab in patients with active rheumatoid arthritis receiving methotrexate.

Methods: In this randomized, double-blind, placebo-controlled, parallel, multiple-dose study, patients who were naive to biologic therapy received infusions of tabalumab (30, 60, or 160 mg) or placebo at weeks 0, 3, and 6 in combination with methotrexate and were evaluated for 24 weeks. The primary efficacy end point was the percentage of patients meeting American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16.

Results: At week 16, the percentages of patients achieving an ACR20 response in the 30-mg (57.6%), 60-mg (67.6%), and 160-mg (51.5%) groups were significantly greater than the percentage of patients achieving an ACR20 response in the placebo group (29.4%; P<0.05). There were initial transient increases from baseline in the frequency of CD20+ and IgD+/CD27- B cells, followed by reductions, although B cells were not completely depleted. Also, the frequency of IgD-/CD27+ B cells increased in all tabalumab groups compared with the placebo group and returned toward baseline levels by the end of the study. The incidence of adverse events was similar across all treatment groups; no deaths occurred. Serum IgM levels decreased significantly in all tabalumab groups combined compared with the placebo group. There were no significant decreases in serum IgG or IgA levels in the tabalumab groups compared with the placebo group.

Conclusion: Tabalumab treatment significantly reduces the signs and symptoms of rheumatoid arthritis and has a safety profile similar to that seen with placebo treatment.

Trial registration: ClinicalTrials.gov NCT00308282.