title: 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.
  
  
  BACKGROUND
  NCT00689728.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, , Palo Alto, CA 94304, USA. Genovese@Stanford.edu
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.forename: Roy M
authors.initials: RM
authors.lastname: Fleischmann
authors.forename: Maria
authors.initials: M
authors.lastname: Greenwald
authors.forename: Julie
authors.initials: J
authors.lastname: Satterwhite
authors.forename: Melissa
authors.initials: M
authors.lastname: Veenhuizen
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Berclaz
authors.forename: Stephen
authors.initials: S
authors.lastname: Myers
authors.forename: Olivier
authors.initials: O
authors.lastname: Benichou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D007275:Injections, Intravenous; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053264:B-Cell Activating Factor; D014409:Tumor Necrosis Factor-alpha; C575974:tabalumab; D008727:Methotrexate