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).

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: Mark C Genovese, Gregg J Silverman, Paul Emery, Ramesh C Gupta, Anne Gill, Melissa Veenhuizen, Li Xie, Wendy J Komocsar, Pierre-Yves Berclaz, Chin Lee
• Journal: Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases (J Clin Rheumatol) Vol. 21 Issue 5 Pg. 231-8 (Aug 2015) ISSN: 1536-7355 [Electronic] United States
• PMID: 26203826 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• B-Cell Activating Factor
• tabalumab

Topics

• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Arthritis, Rheumatoid (drug therapy, immunology)
• B-Cell Activating Factor (antagonists & inhibitors)
• B-Lymphocytes (drug effects, 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