Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moderate-to-severe rheumatoid arthritis and inadequate response to TNF inhibitors: results of a randomised, double-blind, placebo-controlled, phase 3 study
| Autor: | Bernard Combe, Melissa Veenhuizen, R Ortmann, Thomas Dörner, Pierre-Yves Berclaz, Michael Schiff, Chin Lee, Joel M. Kremer, Anne M. Gill, Thomas Huizinga, Wendy J. Komocsar |
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| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Charité Hospital, Humboldt-Universität zu Berlin, Laboratory for Measles and Rubella, Laboratoire National de Santé [Luxembourg] (LNS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty B cells business.industry Immunology Phases of clinical research Rheumatoid Arthritis Autoimmunity medicine.disease Placebo Gastroenterology Rheumatology 3. Good health Tabalumab [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system Rheumatoid arthritis Pharmacodynamics Internal medicine Clinical endpoint Immunology and Allergy Medicine business Adverse effect |
| Zdroj: | RMD Open RMD Open : Rheumatic & Musculoskeletal Diseases RMD Open : Rheumatic & Musculoskeletal Diseases, EULAR ; BMJ, 2015, 1 (1), pp.e000037. ⟨10.1136/rmdopen-2014-000037⟩ |
| ISSN: | 2056-5933 |
| DOI: | 10.1136/rmdopen-2014-000037⟩ |
| Popis: | Background Tabalumab is a human monoclonal antibody that neutralises B-cell activating factor. Objectives To evaluate tabalumab efficacy and safety in patients with rheumatoid arthritis (RA). Methods This phase 3, randomised, double-blind, placebo-controlled study evaluated 456 patients with active RA after 24-week treatment with subcutaneous tabalumab (120 mg every 4 weeks (120/Q4W) or 90 mg every 2 weeks (90/Q2W)) versus placebo, with loading doses (240 or 180 mg) at week 0. Patients were allowed background disease-modifying antirheumatic drugs and previously discontinued ≥1 tumour necrosis factor α inhibitors for lack of efficacy/intolerance. Primary end point was American College of Rheumatology 20% (ACR20) response at 24 weeks. This study was terminated early due to futility. Results Most patients had moderate-to-high baseline disease activity. There was no significant difference in week 24 ACR20 responses between 120/Q4W, 90/Q2W, and placebo (17.6%, 24.3%, 20%) per non-responder imputation analysis. Mean percent changes in CD20+ B-cell count (−10.8%, −9.6%, +10.9%) demonstrated expected pharmacodynamic effects. Treatment-emergent adverse events (AEs) were similar (59.5%, 51.7%, 52.6%), as were AE discontinuations (2.6%, 2.7%, 2.6%), serious AEs (4.6%, 4.1%, 3.9%), serious infectious events (1.3%, 0, 0) and events of interest: infections (23.5%, 25.9%, 24%), injection site reactions (13.1%, 25.8%, 11%) and allergy/hypersensitivity (3.9%, 4.1%, 3.9%) reports. Incidence of treatment-emergent antidrug antibodies was similar to placebo (3.9%, 4.8%, 3.9%). No deaths or new/unexpected safety findings were reported. Conclusions Tabalumab did not demonstrate clinical efficacy in patients with RA in this phase 3 study, despite evidence of biological activity. There were no notable differences in safety parameters between tabalumab treatment groups and placebo. Trial registration number: NCT01202773. |
| Databáze: | OpenAIRE |
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