PMID- 26275429
OWN - NLM
STAT- MEDLINE
DCOM- 20170523
LR  - 20240327
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 75
IP  - 7
DP  - 2016 Jul
TI  - Efficacy and safety of tofacitinib following inadequate response to conventional 
      synthetic or biological disease-modifying antirheumatic drugs.
PG  - 1293-301
LID - 10.1136/annrheumdis-2014-207178 [doi]
AB  - OBJECTIVES: Biological disease-modifying antirheumatic drugs (bDMARDs) have shown 
      diminished clinical response following an inadequate response (IR) to >/=1 previous 
      bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to 
      conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR 
      to bDMARDs (bDMARD-IR). METHODS: Data were taken from phase II and phase III 
      studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients 
      received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with 
      background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates 
      of adverse events (AEs) of special interest were assessed. RESULTS: 2812 
      bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and 
      disease characteristics were generally similar between treatment groups within 
      subpopulations. Across subpopulations, improvements in efficacy parameters at 
      month 3 were generally significantly greater for both tofacitinib doses versus 
      placebo. Clinical response was numerically greater with bDMARD-naive versus 
      bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special 
      interest were generally similar between tofacitinib doses and subpopulations; 
      however, patients receiving glucocorticoids had more serious AEs, 
      discontinuations due to AEs, serious infection events and herpes zoster. 
      Numerically greater clinical responses and incidence rates of AEs of special 
      interest were generally reported for tofacitinib 10 mg twice daily versus 
      tofacitinib 5 mg twice daily (overlapping 95% CIs). CONCLUSIONS: Tofacitinib 
      demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. 
      Clinical response to tofacitinib was generally numerically greater in 
      bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between 
      subpopulations. TRIAL REGISTRATION NUMBERS: (NCT00413660, NCT00550446, 
      NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, 
      NCT00853385).
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/
FAU - Charles-Schoeman, Christina
AU  - Charles-Schoeman C
AD  - University of California, Los Angeles, California, USA.
FAU - Burmester, Gerd
AU  - Burmester G
AD  - Charite-University Medicine Berlin, Berlin, Germany.
FAU - Nash, Peter
AU  - Nash P
AD  - Rheumatology Research Unit, Nambour Hospital, Sunshine Coast, Australia 
      Department of Medicine, University of Queensland, Queensland, Australia.
FAU - Zerbini, Cristiano A F
AU  - Zerbini CA
AD  - Centro Paulista de Investigacao Clinica, Sao Paulo, Brazil.
FAU - Soma, Koshika
AU  - Soma K
AD  - Pfizer Inc, Groton, Connecticut, USA.
FAU - Kwok, Kenneth
AU  - Kwok K
AD  - Pfizer Inc, New York, New York, USA.
FAU - Hendrikx, Thijs
AU  - Hendrikx T
AD  - Pfizer Inc, Collegeville, Pennsylvania, USA.
FAU - Bananis, Eustratios
AU  - Bananis E
AD  - Pfizer Inc, Collegeville, Pennsylvania, USA.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Department of Medicine, Metroplex Clinical Research Center, University of Texas 
      Southwestern Medical Center, Dallas, Texas, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00413660
SI  - ClinicalTrials.gov/NCT00550446
SI  - ClinicalTrials.gov/NCT00603512
SI  - ClinicalTrials.gov/NCT00687193
SI  - ClinicalTrials.gov/NCT00960440
SI  - ClinicalTrials.gov/NCT00847613
SI  - ClinicalTrials.gov/NCT00814307
SI  - ClinicalTrials.gov/NCT00856544
SI  - ClinicalTrials.gov/NCT00853385
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20150814
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 87LA6FU830 (tofacitinib)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
EIN - Ann Rheum Dis. 2017 Mar;76(3):611. PMID: 28213386
MH  - Adult
MH  - Antirheumatic Agents/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Drug Therapy, Combination
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/etiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Methotrexate/adverse effects/therapeutic use
MH  - Middle Aged
MH  - Piperidines/adverse effects/*therapeutic use
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Pyrroles/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC4941182
OTO - NOTNLM
OT  - Anti-TNF
OT  - DMARDs (biologic)
OT  - DMARDs (synthetic)
OT  - Rheumatoid Arthritis
OT  - Treatment
EDAT- 2015/08/16 06:00
MHDA- 2017/05/24 06:00
PMCR- 2016/07/12
CRDT- 2015/08/16 06:00
PHST- 2014/12/18 00:00 [received]
PHST- 2015/07/14 00:00 [accepted]
PHST- 2015/08/16 06:00 [entrez]
PHST- 2015/08/16 06:00 [pubmed]
PHST- 2017/05/24 06:00 [medline]
PHST- 2016/07/12 00:00 [pmc-release]
AID - annrheumdis-2014-207178 [pii]
AID - 10.1136/annrheumdis-2014-207178 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. 
      Epub 2015 Aug 14.