PMID- 27443588
OWN - NLM
STAT- MEDLINE
DCOM- 20171109
LR  - 20220310
IS  - 1532-866X (Electronic)
IS  - 0049-0172 (Linking)
VI  - 46
IP  - 3
DP  - 2016 Dec
TI  - Cardiovascular safety findings in patients with rheumatoid arthritis treated with 
      tofacitinib, an oral Janus kinase inhibitor.
PG  - 261-271
LID - S0049-0172(16)30066-X [pii]
LID - 10.1016/j.semarthrit.2016.05.014 [doi]
AB  - OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of 
      rheumatoid arthritis (RA). The implications of treatment with tofacitinib on 
      cardiovascular (CV) risk in RA are unknown. Therefore, CV adverse events (AEs), 
      and blood pressure and lipid level changes, in tofacitinib-treated patients with 
      RA were evaluated. METHODS: Data were pooled from six Phase (P)3 studies (24 
      months) and two open-label long-term extension (LTE) studies (60 months) of 
      tofacitinib in patients with RA and inadequate response to DMARDs. Tofacitinib 
      was administered alone or with non-biologic DMARDs. CV events, including major 
      adverse CV events (MACE: CV death and non-fatal CV events) and congestive heart 
      failure (CHF), were assessed by a blinded adjudication committee. RESULTS: 
      Overall, 4271 patients from P3 studies and 4827 enrolled from P2/P3 studies into 
      LTE studies were evaluated, representing 3942 and 8699 patient-years of exposure 
      to tofacitinib, respectively. Blood pressure remained stable over time across 
      studies. The number of investigator-reported hypertension-related AEs in 
      tofacitinib-treated patients was low in P3 studies (Months 0-3: 2.8%; Months 3-6: 
      1.4%; >6 months: 2.8%). Across studies, lipid level increases were generally 
      observed within 1-3 months of treatment and stabilized thereafter. Patients with 
      events (incidence rate [IR]/100 patient-years) for MACE and CHF, respectively, 
      were: 23 (0.58) and 9 (0.23) in P3 studies, and 32 (0.37) and 8 (0.09) in LTE 
      studies; IRs were comparable with placebo (P3) and did not increase over time 
      (LTE). CONCLUSIONS: Tofacitinib was associated with a low incidence of CV events 
      in a large Phase 3 program, including LTE studies. Further long-term studies are 
      underway.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Charles-Schoeman, Christina
AU  - Charles-Schoeman C
AD  - University of California, Los Angeles, CA. Electronic address: 
      ccharles@mednet.ucla.edu.
FAU - Wicker, Pierre
AU  - Wicker P
AD  - PW Consulting LLC, Mystic, CT.
FAU - Gonzalez-Gay, Miguel A
AU  - Gonzalez-Gay MA
AD  - Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
FAU - Boy, Mary
AU  - Boy M
AD  - Pfizer Inc., Groton, CT.
FAU - Zuckerman, Andrea
AU  - Zuckerman A
AD  - Pfizer Inc., New London, CT.
FAU - Soma, Koshika
AU  - Soma K
AD  - Pfizer Inc., Groton, CT.
FAU - Geier, Jamie
AU  - Geier J
AD  - Formally of Pfizer Inc., New York, NY.
FAU - Kwok, Kenneth
AU  - Kwok K
AD  - Formally of Pfizer Inc., New York, NY.
FAU - Riese, Richard
AU  - Riese R
AD  - Pfizer Inc., Groton, CT.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160602
PL  - United States
TA  - Semin Arthritis Rheum
JT  - Seminars in arthritis and rheumatism
JID - 1306053
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 0 (Triglycerides)
RN  - 87LA6FU830 (tofacitinib)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Blood Pressure
MH  - Cardiovascular Diseases/*epidemiology/mortality
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Clinical Trials, Phase III as Topic
MH  - Heart Failure/epidemiology
MH  - Humans
MH  - Hyperlipidemias/blood/*epidemiology
MH  - Hypertension/epidemiology
MH  - Incidence
MH  - Janus Kinases/antagonists & inhibitors
MH  - Piperidines/*therapeutic use
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Pyrimidines/*therapeutic use
MH  - Pyrroles/*therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Triglycerides/blood
OTO - NOTNLM
OT  - Cardiovascular
OT  - Rheumatoid arthritis
OT  - Safety
OT  - Tofacitinib
EDAT- 2016/07/23 06:00
MHDA- 2017/11/10 06:00
CRDT- 2016/07/23 06:00
PHST- 2015/10/08 00:00 [received]
PHST- 2016/04/29 00:00 [revised]
PHST- 2016/05/27 00:00 [accepted]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2017/11/10 06:00 [medline]
PHST- 2016/07/23 06:00 [entrez]
AID - S0049-0172(16)30066-X [pii]
AID - 10.1016/j.semarthrit.2016.05.014 [doi]
PST - ppublish
SO  - Semin Arthritis Rheum. 2016 Dec;46(3):261-271. doi: 
      10.1016/j.semarthrit.2016.05.014. Epub 2016 Jun 2.