PMID- 21584942
OWN - NLM
STAT- MEDLINE
DCOM- 20111003
LR  - 20220409
IS  - 2151-4658 (Electronic)
IS  - 2151-464X (Linking)
VI  - 63
IP  - 8
DP  - 2011 Aug
TI  - Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients 
      with rheumatoid arthritis and an inadequate response to methotrexate.
PG  - 1150-8
LID - 10.1002/acr.20494 [doi]
AB  - OBJECTIVE: To compare the efficacy, safety, and tolerability of 4 doses of oral 
      tofacitinib (CP-690,550) with placebo in Japanese patients with active rheumatoid 
      arthritis (RA) receiving stable background methotrexate (MTX) who had an 
      inadequate response to MTX alone. METHODS: A total of 140 patients were 
      randomized to receive tofacitinib 1, 3, 5, and 10 mg twice a day or placebo in 
      this 12-week, phase II, double-blind study. All patients remained on background 
      MTX. Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12. The primary 
      efficacy end point was the American College of Rheumatology 20% improvement 
      criteria (ACR20) response rate at week 12. RESULTS: ACR20 response rates at week 
      12 were significant (P < 0.0001) for all tofacitinib treatment groups: 1 mg twice 
      a day, 64.3%; 3 mg twice a day, 77.8%; 5 mg twice a day, 96.3%; and 10 mg twice a 
      day, 80.8% versus placebo, 14.3%. A significant dose-response relationship for 
      the ACR20 was observed (P < 0.0001). Low disease activity was achieved by 72.7% 
      of patients with high baseline disease activity for tofacitinib 10 mg twice a day 
      at week 12 (P < 0.0001). Significant improvements in the ACR50, ACR70, Health 
      Assessment Questionnaire Disability Index, and Disease Activity Score 28-3 
      (C-reactive protein) were also reported. The most commonly reported adverse 
      events (AEs) were nasopharyngitis (n = 13) and increased alanine aminotransferase 
      (n = 12) and aspartate aminotransferase (n = 9) levels. These AEs were mild or 
      moderate in severity. Serious AEs were reported by 5 patients. No deaths 
      occurred. CONCLUSION: In Japanese patients with active RA with an inadequate 
      response to MTX, tofacitinib in combination with MTX over 12 weeks was 
      efficacious and had a manageable safety profile.
CI  - Copyright (c) 2011 by the American College of Rheumatology.
FAU - Tanaka, Yoshiya
AU  - Tanaka Y
AD  - First Department of Internal Medicine, School of Medicine, University of 
      Occupational and Environmental Health Japan, Iseigaoka, Yahatanishi, Kitakyushu, 
      Japan. tanaka@med.uoeh-u.ac.jp
FAU - Suzuki, Makoto
AU  - Suzuki M
FAU - Nakamura, Hiroyuki
AU  - Nakamura H
FAU - Toyoizumi, Shigeyuki
AU  - Toyoizumi S
FAU - Zwillich, Samuel H
AU  - Zwillich SH
CN  - Tofacitinib Study Investigators
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Care Res (Hoboken)
JT  - Arthritis care & research
JID - 101518086
RN  - 0 (Antibodies, Monoclonal)
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  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
CIN - Mod Rheumatol. 2016;26(2):318-9. PMID: 25671402
MH  - Adult
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antirheumatic Agents/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Female
MH  - Humans
MH  - *Immunomodulation
MH  - Janus Kinase 3/antagonists & inhibitors
MH  - Longitudinal Studies
MH  - Male
MH  - Methotrexate/*administration & dosage
MH  - Middle Aged
MH  - Piperidines
MH  - Pyrimidines/*administration & dosage
MH  - Pyrroles/*administration & dosage
MH  - Treatment Outcome
FIR - Kondo, Hirobumi
IR  - Kondo H
FIR - Matsumura, Ryutaro
IR  - Matsumura R
FIR - Miyasaka, Nobuyuki
IR  - Miyasaka N
FIR - Mori, Shunsuke
IR  - Mori S
FIR - Munakata, Yasuhiko
IR  - Munakata Y
FIR - Nakano, Masaaki
IR  - Nakano M
FIR - Ohshima, Hisaji
IR  - Ohshima H
FIR - Ohshima, Shiro
IR  - Ohshima S
FIR - Ohta, Shuji
IR  - Ohta S
FIR - Suematsu, Eiichi
IR  - Suematsu E
FIR - Takeuchi, Tsutomu
IR  - Takeuchi T
FIR - Yamamoto, Kazuhiko
IR  - Yamamoto K
FIR - Takasaki, Yoshinari
IR  - Takasaki Y
FIR - Tanaka, Yoshiya
IR  - Tanaka Y
FIR - Tohma, Shigeto
IR  - Tohma S
FIR - Tsuda, Hiroshi
IR  - Tsuda H
FIR - Yamagata, Hajime
IR  - Yamagata H
FIR - Yamanaka, Hisashi
IR  - Yamanaka H
FIR - Yamanaka, Kenjiro
IR  - Yamanaka K
EDAT- 2011/05/18 06:00
MHDA- 2011/10/04 06:00
CRDT- 2011/05/18 06:00
PHST- 2011/05/18 06:00 [entrez]
PHST- 2011/05/18 06:00 [pubmed]
PHST- 2011/10/04 06:00 [medline]
AID - 10.1002/acr.20494 [doi]
PST - ppublish
SO  - Arthritis Care Res (Hoboken). 2011 Aug;63(8):1150-8. doi: 10.1002/acr.20494.