Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis with an inadequate response to TNF inhibitors.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of tabalumab, a monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with active rheumatoid arthritis (RA) who showed inadequate response to tumour necrosis factor (TNF) inhibitors.

METHODS:

Patients on stable methotrexate and with inadequate response to one or more TNF inhibitors were randomised to placebo (n=35), 30 mg tabalumab (n=35) or 80 mg tabalumab (n=30) given intravenously at 0, 3 and 6 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology 50% response (ACR50) at week 16 (all tabalumab-treated patients vs placebo).

RESULTS:

At week 16, no significant differences were observed in the combined tabalumab group versus placebo in ACR50 (12.7% vs 2.9%, p=0.101) or ACR20 response rates (27.0% vs 17.1%, p=0.198). However, significant differences between the combined tabalumab group and placebo were observed at earlier time points for ACR20, ACR50 and Disease Activity Score in 28 joints (DAS28)-C-reactive protein (CRP) reduction. Treatment-emergent adverse events (AEs) were similar with 30 mg tabalumab (65.7%), 80 mg tabalumab (76.7%) and placebo (71.4%), although certain events occurred more often with tabalumab than placebo (eg, infection, anaemia and gastrointestinal events). Serious AEs occurred in two (6.7%) patients receiving 80 mg tabalumab and three (8.6%) receiving placebo, with one serious infection in the placebo group. Initial increases in total and mature B cells were followed by progressive decreases, despite declines in serum tabalumab.

CONCLUSIONS:

At week 16, the primary end point was not achieved, but an indication of efficacy was observed at earlier time points. Safety findings for tabalumab were consistent with other biological RA therapies.

CLINICAL TRIAL REGISTRATION NUMBER:

NCT00689728.

• Authors: Mark C Genovese, Roy M Fleischmann, Maria Greenwald, Julie Satterwhite, Melissa Veenhuizen, Li Xie, Pierre-Yves Berclaz, Stephen Myers, Olivier Benichou
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 72 Issue 9 Pg. 1461-8 (Sep 01 2013) ISSN: 1468-2060 [Electronic] England
• PMID: 23268367 (Publication Type: 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
• Tumor Necrosis Factor-alpha
• tabalumab
• Methotrexate

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (administration & dosage, adverse effects, therapeutic use)
• Arthritis, Rheumatoid (drug therapy, physiopathology)
• B-Cell Activating Factor (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Resistance
• Drug Therapy, Combination
• Female
• Health Status
• Humans
• Injections, Intravenous
• Joints (drug effects, physiopathology)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Severity of Illness Index
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)
• Young Adult