PMID- 26535134
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151104
LR  - 20181113
IS  - 2056-5933 (Print)
IS  - 2056-5933 (Electronic)
IS  - 2056-5933 (Linking)
VI  - 1
IP  - 1
DP  - 2015
TI  - 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.
PG  - e000037
LID - 10.1136/rmdopen-2014-000037 [doi]
LID - e000037
AB  - 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 alpha 
      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.
FAU - Schiff, Michael
AU  - Schiff M
AD  - Rheumatology Division , School of Medicine, University of Colorado , Denver , 
      USA.
FAU - Combe, Bernard
AU  - Combe B
AD  - Department of Rheumatology , Lapeyronie Hospital, Montpellier 1 University , 
      Montpellier , France.
FAU - Dorner, Thomas
AU  - Dorner T
AD  - Department of Medicine/Rheumatology and Clinical Immunology , 
      Charite-Universitatsmedizin Berlin , Berlin , Germany.
FAU - Kremer, Joel M
AU  - Kremer JM
AD  - Division of Rheumatology , Albany Medical College , Albany , USA.
FAU - Huizinga, Thomas W
AU  - Huizinga TW
AD  - Department of Rheumatology , Leiden University Medical Center , Leiden , The 
      Netherlands.
FAU - Veenhuizen, Melissa
AU  - Veenhuizen M
AD  - Global Patient Safety Medical and Benefit-Risk Management, Lilly and Company , 
      Indianapolis , USA.
FAU - Gill, Anne
AU  - Gill A
AD  - Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , 
      Indianapolis , USA.
FAU - Komocsar, Wendy
AU  - Komocsar W
AD  - Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , 
      Indianapolis , USA.
FAU - Berclaz, Pierre-Yves
AU  - Berclaz PY
AD  - Medical Science-Japan Development, Lilly and Company , Kobe , Japan.
FAU - Ortmann, Robert
AU  - Ortmann R
AD  - Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , 
      Indianapolis , USA.
FAU - Lee, Chin
AU  - Lee C
AD  - Autoimmune Medical, Bio-Medicines Business Unit , Lilly and Company , 
      Indianapolis , USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01202773
PT  - Journal Article
DEP - 20150812
PL  - England
TA  - RMD Open
JT  - RMD open
JID - 101662038
PMC - PMC4623366
OTO - NOTNLM
OT  - Autoimmunity
OT  - B cells
OT  - Rheumatoid Arthritis
EDAT- 2015/11/05 06:00
MHDA- 2015/11/05 06:01
PMCR- 2015/08/12
CRDT- 2015/11/05 06:00
PHST- 2014/12/11 00:00 [received]
PHST- 2015/05/03 00:00 [revised]
PHST- 2015/06/18 00:00 [accepted]
PHST- 2015/11/05 06:00 [entrez]
PHST- 2015/11/05 06:00 [pubmed]
PHST- 2015/11/05 06:01 [medline]
PHST- 2015/08/12 00:00 [pmc-release]
AID - rmdopen-2014-000037 [pii]
AID - 10.1136/rmdopen-2014-000037 [doi]
PST - epublish
SO  - RMD Open. 2015 Aug 12;1(1):e000037. doi: 10.1136/rmdopen-2014-000037. eCollection 
      2015.