A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate. Issue 9 (18th April 2013)

• Record Type: Journal Article
• Authors: Genovese, Mark C; Lee, Eric; Satterwhite, Julie; Veenhuizen, Melissa; Disch, Damon; Berclaz, Pierre-Yves; Myers, Stephen; Sides, Gregory; Benichou, Olivier
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Issue 9(2013)
• Page Start: 1453
• Page End: 1460
• Publication Date: 2013-04-18
• Subjects: Rheumatoid Arthritis -- TNF-alpha -- Autoimmune Diseases -- B cells; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-202864
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: To assess the dose-response relationship, efficacy and safety of tabalumab, a human monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX). Methods: In this phase 2, 24-week, double-blind, placebo-controlled, dose-ranging study, patients with RA (N=158) on stable MTX were randomised by Bayesian-adaptive method to receive 1, 3, 10, 30, 60, or 120 mg tabalumab or placebo subcutaneously every 4 weeks for 24 weeks. The primary objective was to test for a significant dose-response relationship using a statistical model of the proportion of patients having ≥50% improvement in American College of Rheumatology (ACR) criteria (ACR50) at week 24 (prespecified α=0.10). Results: At week 24, a significant dose-response relationship was observed using ACR50 (p=0.059) and ACR20 (p=0.044) response rates. Using model-estimated data, only 120 mg had significantly higher ACR50 and ACR20 response rates versus placebo (p<0.05). Observed response rates were significantly higher for 120 mg versus placebo as measured by ACR50 at weeks 12 (p=0.039) and 20 (p=0.018), but not week 24, and by ACR20 at weeks 12 (p=0.011) and 24 (p=0.039). Mean DAS28 C-reactive protein improved with 120 mg at week 24 (p=0.048). Frequency of TEAEs was similar across groups (range 50–69%, p=0.884). Ten (8.2%) tabalumab and 5 (13.9%) placebo patients reported a serious adverse event (SAE). Infections occurred more frequently in patients exposed to tabalumab (30.3% vs 19.4%). Serious infections were reported in 3 (2.5%) tabalumab-treated patients only. Conclusions: A dose-response relationship was detected with monthly subcutaneous tabalumab. A significant effect was detected with the 120 mg dose with no unexpected safety signals. Clinical Trial #: NCT00785928.