title: 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.
abstract: BACKGROUND
  Tabalumab is a human monoclonal antibody that neutralises B-cell activating factor.
  
  
  OBJECTIVE
  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.
  
  
  BACKGROUND
  NCT01202773.
authors.affiliation: Rheumatology Division , School of Medicine, University of Colorado , Denver , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Schiff
authors.affiliation: Department of Rheumatology , Lapeyronie Hospital, Montpellier 1 University , Montpellier , France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
authors.affiliation: Department of Medicine/Rheumatology and Clinical Immunology , Charité-Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.affiliation: Division of Rheumatology , Albany Medical College , Albany , USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Kremer
authors.affiliation: Department of Rheumatology , Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Global Patient Safety Medical and Benefit-Risk Management, Lilly and Company , Indianapolis , USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Veenhuizen
authors.affiliation: Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , Indianapolis , USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Gill
authors.affiliation: Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , Indianapolis , USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Komocsar
authors.affiliation: Medical Science-Japan Development, Lilly and Company , Kobe , Japan.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Berclaz
authors.affiliation: Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , Indianapolis , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ortmann
authors.affiliation: Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , Indianapolis , USA.
authors.forename: Chin
authors.initials: C
authors.lastname: Lee
keywords: Autoimmunity; B cells; Rheumatoid Arthritis