Efficacy and Safety of Tabalumab, an Anti-B-Cell-Activating Factor Monoclonal Antibody, in a Heterogeneous Rheumatoid Arthritis Population: Results From a Randomized, Placebo-Controlled, Phase 3 Trial (FLEX-O)

• Published in: Journal of clinical rheumatology Vol. 21; no. 5; p. 231
• Main Authors: Genovese, Mark C, Silverman, Gregg J, Emery, Paul, Gupta, Ramesh C, Gill, Anne, Veenhuizen, Melissa, Xie, Li, Komocsar, Wendy J, Berclaz, Pierre-Yves, Lee, Chin
• Format: Journal Article
• Language: English
• Published: United States 01.08.2015
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; B-Cell Activating Factor - antagonists & inhibitors; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Patient Safety; Severity of Illness Index; Treatment Outcome
• ISSN: 1536-7355
• DOI: 10.1097/RHU.0000000000000276

The efficacy and safety of 2 different dosing regimens of tabalumab, a monoclonal antibody that neutralizes membrane-bound and soluble B-cell-activating factor (BAFF), were evaluated in patients with rheumatoid arthritis. In this phase 3, multicenter, randomized study, 1004 patients (intention-to-treat population) received subcutaneous 120 mg tabalumab every 4 weeks (120/Q4W), 90 mg tabalumab every 2 weeks (90/Q2W), or placebo over 24 weeks. At baseline, a loading dose double the planned dose (ie, 240 mg, 180 mg, or placebo) was administered. Efficacy analyses were based on a prespecified subset of patients with 5 or more of 68 tender and 5 or more of 66 swollen joints at baseline (efficacy population, n = 849). The primary efficacy end point was ACR20 (20% improvement in American College of Rheumatology criteria) response at week 24. At week 24, there were no differences in ACR20 response rates (120/Q4W = 34.4%, 90/Q2W = 33.5%, placebo = 31.5%) or any other measures of efficacy across the treatment groups. Discontinuations due to adverse events (AE) were 3.4%, 2.7%, and 4.0%; incidence of treatment-emergent AEs were 64.1%, 58.2%, and 58.8%, with 23.2%, 25.9%, and 22.0% treatment-emergent infections; and incidence rates of serious AEs were 3.7%, 2.2%, and 2.8% with 1.1%, 0.3%, and 0.7% serious infections in the 120/Q4W, 90/Q2W, and placebo groups, respectively. Three deaths were reported (120/Q4W, n = 2; 90/Q2W, n = 1). Each tabalumab group had significant decreases versus placebo in CD3-CD20 B cells (P ≤ 0.05) and in serum immunoglobulins (P ≤ 0.001). Although tabalumab administration resulted in biologic activity, as demonstrated by changes in B cells and immunoglobulins, targeting BAFF-dependent pathways alone is not sufficient to significantly reduce rheumatoid arthritis disease activity.