title: Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: results from a phase III multicentre, randomised, double-blind study.
abstract: OBJECTIVE
  Randomised, double-blind, placebo-controlled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR).
  
  
  METHODS
  1041 patients with moderate-severe RA despite ongoing MTX enrolled in a 52-week study evaluating subcutaneous tabalumab 120 mg every four weeks (120/Q4W) or 90 mg every two weeks (90/Q2W) versus placebo. Primary endpoints were American College of Rheumatology 20% (ACR20) response rate and Health Assessment Questionnaire-Disability Index change from baseline at 24 weeks and modified Total Sharp Score (mTSS) change at 52 weeks.
  
  
  RESULTS
  There were no significant differences in ACR20 responses at week 24 or mTSS change from baseline at week 52 among treatment groups. Declines were seen in CD20+ B cells and immunoglobulin levels in tabalumab groups, but not placebo: B cells (-15.0%, -18.8%, 5.3%, in the 120/Q4W, 90/Q2W, and placebo groups, respectively); IgM (-16.3%, -19.4%, -0.1%), IgA (-11.4%, -4.7%, 1.2%) and IgG (-8.6%, -7.8%, 0.1%). Discontinuations due to adverse events were similar between groups. Numerically more serious infections were reported in tabalumab groups (1.7%, 0.6%, 0.3%); numerically more injection-site reactions were reported in the 90/Q2W group (2.3%, 4.3%, 2.3%).
  
  
  CONCLUSIONS
  Neither clinical efficacy nor significant safety signals were observed with tabalumab despite evidence of biological activity. This study was terminated early due to insufficient efficacy.
  
  
  BACKGROUND
  NCT01198002.
authors: Division of Rheumatology, Department of Medicine 3, Medical University of Vienna and Hietzing Hospital, Vienna, Austria.
authors: Josef S
authors: JS
authors: Smolen
authors: Department of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Michael E
authors: ME
authors: Weinblatt
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Désirée
authors: http://orcid.org/0000-0002-5781-158X
authors: D
authors: van der Heijde
authors: The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors: William F C
authors: WF
authors: Rigby
authors: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Ronald
authors: R
authors: van Vollenhoven
authors: Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Clifton O
authors: CO
authors: Bingham
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Melissa
authors: M
authors: Veenhuizen
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Anne
authors: A
authors: Gill
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Fangyi
authors: F
authors: Zhao
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Wendy J
authors: WJ
authors: Komocsar
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Pierre-Yves
authors: PY
authors: Berclaz
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Robert
authors: R
authors: Ortmann
authors: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Chin
authors: C
authors: Lee
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D006801:Humans; D057194:Intention to Treat Analysis; D008727:Methotrexate / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; C575974:tabalumab; D008727:Methotrexate
keywords: Autoimmune Diseases; B cells; Rheumatoid Arthritis