PMID- 21952978
OWN - NLM
STAT- MEDLINE
DCOM- 20120710
LR  - 20220409
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 64
IP  - 3
DP  - 2012 Mar
TI  - Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) 
      or adalimumab monotherapy versus placebo in patients with active rheumatoid 
      arthritis with an inadequate response to disease-modifying antirheumatic drugs.
PG  - 617-29
LID - 10.1002/art.33383 [doi]
AB  - OBJECTIVE: To compare the efficacy, safety, and tolerability of 5 doses of oral 
      tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment 
      of active rheumatoid arthritis (RA) in patients with an inadequate response to 
      disease-modifying antirheumatic drugs. METHODS: In this 24-week, double-blind, 
      phase IIb study, patients with RA (n = 384) were randomized to receive placebo, 
      tofacitinib at 1, 3, 5, 10, or 15 mg administered orally twice a day, or 
      adalimumab at 40 mg injected subcutaneously every 2 weeks (total of 6 injections) 
      followed by oral tofacitinib at 5 mg twice a day for 12 weeks. The primary end 
      point was the responder rate according to the American College of Rheumatology 
      20% improvement criteria (ACR20) at week 12. RESULTS: Treatment with tofacitinib 
      at a dose of >/=3 mg twice a day resulted in a rapid response with significant 
      efficacy when compared to placebo, as indicated by the primary end point (ACR20 
      response at week 12), achieved in 39.2% (3 mg; P </= 0.05), 59.2% (5 mg; P < 
      0.0001), 70.5% (10 mg; P < 0.0001), and 71.9% (15 mg; P < 0.0001) in the 
      tofacitinib group and 35.9% of patients in the adalimumab group (P = 0.105), 
      compared with 22.0% of patients receiving placebo. Improvements were sustained at 
      week 24, according to the ACR20, ACR50, and ACR70 response rates as well as 
      classifications of remission according to the 3-variable Disease Activity Score 
      in 28 joints (DAS28) using C-reactive protein and the 4-variable DAS28 using the 
      erythrocyte sedimentation rate. The most common treatment-emergent adverse events 
      (AEs) in patients across all tofacitinib treatment arms (n = 272) were urinary 
      tract infection (7.7%), diarrhea (4.8%), headache (4.8%), and bronchitis (4.8%). 
      CONCLUSION: Tofacitinib monotherapy at >/=3 mg twice a day was efficacious in the 
      treatment of patients with active RA over 24 weeks and demonstrated a manageable 
      safety profile.
CI  - Copyright (c) 2012 by the American College of Rheumatology.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Metroplex Clinical Research Center and University of Texas Southwestern Medical 
      Center, Dallas, TX 75231, USA. rfleischmann@arthdocs.com
FAU - Cutolo, Maurizio
AU  - Cutolo M
FAU - Genovese, Mark C
AU  - Genovese MC
FAU - Lee, Eun Bong
AU  - Lee EB
FAU - Kanik, Keith S
AU  - Kanik KS
FAU - Sadis, Seth
AU  - Sadis S
FAU - Connell, Carol A
AU  - Connell CA
FAU - Gruben, David
AU  - Gruben D
FAU - Krishnaswami, Sriram
AU  - Krishnaswami S
FAU - Wallenstein, Gene
AU  - Wallenstein G
FAU - Wilkinson, Bethanie E
AU  - Wilkinson BE
FAU - Zwillich, Samuel H
AU  - Zwillich SH
LA  - eng
SI  - ClinicalTrials.gov/NCT00550446
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 87LA6FU830 (tofacitinib)
RN  - EC 2.7.10.2 (Janus Kinase 3)
RN  - FYS6T7F842 (Adalimumab)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adalimumab
MH  - Administration, Oral
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*therapeutic use
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - *Drug Substitution
MH  - Drug Tolerance
MH  - Female
MH  - Health Status
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Janus Kinase 3/antagonists & inhibitors
MH  - Joints/drug effects/physiopathology
MH  - Male
MH  - Methotrexate/therapeutic use
MH  - Middle Aged
MH  - Pilot Projects
MH  - Piperidines
MH  - Pyrimidines/administration & dosage/*therapeutic use
MH  - Pyrroles/administration & dosage/*therapeutic use
MH  - Recovery of Function
EDAT- 2011/09/29 06:00
MHDA- 2012/07/11 06:00
CRDT- 2011/09/29 06:00
PHST- 2011/09/29 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/07/11 06:00 [medline]
AID - 10.1002/art.33383 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2012 Mar;64(3):617-29. doi: 10.1002/art.33383.