PMID- 32419304
OWN - NLM
STAT- MEDLINE
DCOM- 20210106
LR  - 20210110
IS  - 2326-5205 (Electronic)
IS  - 2326-5191 (Print)
IS  - 2326-5191 (Linking)
VI  - 72
IP  - 10
DP  - 2020 Oct
TI  - Efficacy and Safety of PF-06651600 (Ritlecitinib), a Novel JAK3/TEC Inhibitor, in 
      Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response 
      to Methotrexate.
PG  - 1621-1631
LID - 10.1002/art.41316 [doi]
AB  - OBJECTIVE: To evaluate the efficacy and safety of PF-06651600 (ritlecitinib), an 
      irreversible inhibitor of JAK3 and the tyrosine kinase expressed in 
      hepatocellular carcinoma (TEC) kinase family, in comparison with placebo in 
      patients with rheumatoid arthritis (RA). METHODS: An 8-week, phase II, 
      double-blind, parallel-group study was conducted. Seventy patients who were 
      seropositive for anti-citrullinated protein antibodies and/or rheumatoid factor 
      were randomized 3:2 to receive oral PF-06651600 (200 mg once daily) or placebo 
      for 8 weeks. Eligible patients had an inadequate response to methotrexate, and 
      the study design allowed up to 50% of patients to have previously received 1 
      tumor necrosis factor inhibitor that was inadequately effective and/or not 
      tolerated. The primary end point was change from baseline in the Simplified 
      Disease Activity Index (SDAI) score at week 8, assessed by Bayesian analysis 
      using an informative prior distribution for placebo response. RESULTS: Mean 
      change from baseline in the SDAI score at week 8 was greater in the PF-06651600 
      group (-26.1 [95% credible interval -29.7, -22.4]) than in the placebo group 
      (-16.8 [95% credible interval -20.9, -12.7]; P < 0.001). Most adverse events 
      (AEs) were mild in severity, and no treatment-related serious AEs, severe AEs, or 
      deaths were reported. The most common classes of AE were infections and 
      infestations as well as skin and subcutaneous tissue disorders; there was 1 mild 
      case of herpes simplex in the PF-06651600 group that was considered to be 
      treatment related, which resolved within 3 days without study treatment 
      discontinuation or antiviral therapy. CONCLUSION: Treatment with the oral 
      JAK3/TEC inhibitor PF-06651600 (200 mg once daily) was associated with 
      significant improvements in RA disease activity and was generally well-tolerated 
      in this small 8-week study.
CI  - (c) 2020 Pfizer Inc. Arthritis & Rheumatology published by Wiley Periodicals LLC on 
      behalf of American College of Rheumatology.
FAU - Robinson, Michael F
AU  - Robinson MF
AD  - California Medical Research Associates, Northridge.
FAU - Damjanov, Nemanja
AU  - Damjanov N
AD  - University of Belgrade School of Medicine, Belgrade, Serbia.
FAU - Stamenkovic, Bojana
AU  - Stamenkovic B
AD  - Institute for Treatment and Rehabilitation Niska Banja and Nis University School 
      of Medicine, Nis, Serbia.
FAU - Radunovic, Goran
AU  - Radunovic G
AD  - University of Belgrade School of Medicine, Belgrade, Serbia.
FAU - Kivitz, Alan
AU  - Kivitz A
AD  - Altoona Center for Clinical Research, Duncansville, Pennsylvania.
FAU - Cox, Lori
AU  - Cox L
AD  - Pfizer, Inc., New York, New York.
FAU - Manukyan, Zorayr
AU  - Manukyan Z
AD  - Pfizer, Inc., New York, New York.
FAU - Banfield, Christopher
AU  - Banfield C
AD  - Pfizer, Inc., New York, New York.
FAU - Saunders, Michael
AU  - Saunders M
AD  - Pfizer, Inc., New York, New York.
FAU - Chandra, Deepa
AU  - Chandra D
AD  - Pfizer, Inc., New York, New York.
FAU - Vincent, Michael S
AU  - Vincent MS
AD  - Pfizer, Inc., New York, New York.
FAU - Mancuso, Jessica
AU  - Mancuso J
AD  - Pfizer, Inc., Groton, Connecticut.
FAU - Peeva, Elena
AU  - Peeva E
AD  - Pfizer, Inc., New York, New York.
FAU - Beebe, Jean S
AU  - Beebe JS
AD  - Pfizer, Inc., New York, New York.
LA  - eng
SI  - ClinicalTrials.gov/NCT02969044
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200907
PL  - United States
TA  - Arthritis Rheumatol
JT  - Arthritis & rheumatology (Hoboken, N.J.)
JID - 101623795
RN  - 0 (Antirheumatic Agents)
RN  - 0 (PF-06651600)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - EC 2.7.10.2 (Janus Kinase 3)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antirheumatic Agents/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Janus Kinase 3/*antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/adverse effects/*therapeutic use
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Pyrroles/adverse effects/*therapeutic use
MH  - Treatment Outcome
PMC - PMC7589242
EDAT- 2020/05/19 06:00
MHDA- 2021/01/07 06:00
PMCR- 2020/10/27
CRDT- 2020/05/19 06:00
PHST- 2019/06/12 00:00 [received]
PHST- 2020/05/13 00:00 [accepted]
PHST- 2020/05/19 06:00 [pubmed]
PHST- 2021/01/07 06:00 [medline]
PHST- 2020/05/19 06:00 [entrez]
PHST- 2020/10/27 00:00 [pmc-release]
AID - ART41316 [pii]
AID - 10.1002/art.41316 [doi]
PST - ppublish
SO  - Arthritis Rheumatol. 2020 Oct;72(10):1621-1631. doi: 10.1002/art.41316. Epub 2020 
      Sep 7.