A phase 2 dose-ranging study of subcutaneous tabalumab for the treatment of patients with active rheumatoid arthritis and an inadequate response to methotrexate

• Published in: Annals of the rheumatic diseases Vol. 72; no. 9; p. 1453
• Main Authors: Genovese, Mark C, Lee, Eric, Satterwhite, Julie, Veenhuizen, Melissa, Disch, Damon, Berclaz, Pierre-Yves, Myers, Stephen, Sides, Gregory, Benichou, Olivier
• Format: Journal Article
• Language: English
• Published: England 01-09-2013
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - pharmacokinetics; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - physiopathology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Health Status; Humans; Injections, Subcutaneous; Joints - drug effects; Joints - pathology; Joints - physiopathology; Male; Methotrexate - therapeutic use; Middle Aged; Pilot Projects; Severity of Illness Index; Treatment Outcome; Young Adult; B cells; Rheumatoid Arthritis; TNF-alpha; Autoimmune Diseases
• ISSN: 1468-2060
• DOI: 10.1136/annrheumdis-2012-202864

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).
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).
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.
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.