Risk Factors for Major Adverse Cardiovascular Events in Phase III and Long-Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis.
Aged
Arthritis, Rheumatoid
/ blood
Blood Sedimentation
Cardiovascular Diseases
/ epidemiology
Cholesterol
/ blood
Cholesterol, HDL
/ blood
Cholesterol, LDL
/ blood
Clinical Trials, Phase III as Topic
Female
Humans
Incidence
Male
Middle Aged
Myocardial Infarction
/ epidemiology
Piperidines
/ therapeutic use
Proportional Hazards Models
Protein Kinase Inhibitors
/ therapeutic use
Pyrimidines
/ therapeutic use
Pyrroles
/ therapeutic use
Risk Factors
Stroke
/ epidemiology
Treatment Outcome
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
15
03
2018
accepted:
11
04
2019
pubmed:
7
8
2019
medline:
6
2
2020
entrez:
7
8
2019
Statut:
ppublish
Résumé
Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). This study was undertaken to evaluate the risk of major adverse cardiovascular events (MACE) in patients with RA receiving tofacitinib. Data were pooled from patients with moderately to severely active RA receiving ≥1 tofacitinib dose in 6 phase III and 2 long-term extension studies over 7 years. MACE (myocardial infarction, stroke, cardiovascular death) were independently adjudicated. Cox regression models were used to evaluate associations between baseline variables and time to first MACE. Following 24 weeks of tofacitinib, changes in variables and time to future MACE were evaluated after adjusment for age, baseline values, and time-varying tofacitinib dose. Hazard ratios and 95% confidence intervals were calculated. Fifty-two MACE occurred in 4,076 patients over 12,873 patient-years of exposure (incidence rate 0.4 patients with events per 100 patient-years). In univariable analyses of baseline variables, traditional cardiovascular risk factors and glucocorticoid and statin use were associated with MACE risk; disease activity and inflammation measures were not. In subsequent multivariable analyses, baseline age, hypertension, and the total cholesterol to high-density lipoprotein (HDL) cholesterol ratio remained significantly associated with risk of MACE. After 24 weeks of treatment, an increase in HDL cholesterol and a decrease in the total to HDL cholesterol were associated with decreased MACE risk; changes in total cholesterol, low-density lipoprotein (LDL) cholesterol, and disease activity measures were not. Increased erythrocyte sedimentation rates trended with increased future MACE risk. In this post hoc analysis, after 24 weeks of tofacitinib treatment, increased HDL cholesterol, but not increased LDL cholesterol or total cholesterol, appeared to be associated with lower future MACE risk. Further data are needed to test the cardiovascular safety of tofacitinib.
Identifiants
pubmed: 31385441
doi: 10.1002/art.40911
pmc: PMC6754249
mid: NIHMS1044055
doi:
Substances chimiques
Cholesterol, HDL
0
Cholesterol, LDL
0
Piperidines
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Pyrroles
0
tofacitinib
87LA6FU830
Cholesterol
97C5T2UQ7J
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1450-1459Subventions
Organisme : Pfizer Inc
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL123064
Pays : United States
Informations de copyright
© 2019, Pfizer Inc. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
Références
Eur Heart J. 2012 Jul;33(13):1635-701
pubmed: 22555213
Am Heart J. 2014 Dec;168(6):878-83.e1
pubmed: 25458651
Ann Rheum Dis. 2012 Sep;71(9):1524-9
pubmed: 22425941
Ann Rheum Dis. 2015 Apr;74(4):694-702
pubmed: 24368514
Can J Cardiol. 1988 Jul;4 Suppl A:5A-10A
pubmed: 3179802
Ann Rheum Dis. 2017 Jan;76(1):17-28
pubmed: 27697765
N Engl J Med. 2012 Aug 9;367(6):508-19
pubmed: 22873531
Rheumatology (Oxford). 2010 Feb;49(2):295-307
pubmed: 19946022
Arthritis Rheum. 2009 Jul;60(7):1895-905
pubmed: 19565475
N Engl J Med. 2012 Aug 9;367(6):495-507
pubmed: 22873530
Arthritis Rheum. 2008 Dec 15;59(12):1690-7
pubmed: 19035419
N Engl J Med. 2014 Jun 19;370(25):2377-86
pubmed: 24941177
Arthritis Res Ther. 2016 Jan 28;18:34
pubmed: 26818974
Arthritis Res Ther. 2019 Apr 5;21(1):89
pubmed: 30953540
Rheumatology (Oxford). 2014 Dec;53(12):2143-54
pubmed: 24907149
Arthritis Rheumatol. 2015 May;67(8):2004-10
pubmed: 25917955
Ann Rheum Dis. 2007 Jan;66(1):76-80
pubmed: 16818462
Eur Heart J. 2015 Jan 1;36(1):10-2
pubmed: 25148836
Circulation. 1991 Jan;83(1):356-62
pubmed: 1984895
Rheumatology (Oxford). 2007 Feb;46(2):350-7
pubmed: 16908509
Arthritis Rheumatol. 2015 Feb;67(2):372-80
pubmed: 25332171
Ann Rheum Dis. 2010 Jul;69(7):1310-4
pubmed: 19854708
Arthritis Rheum. 2001 Dec;44(12):2737-45
pubmed: 11762933
Thromb Haemost. 2009 Aug;102(2):215-22
pubmed: 19652871
Joint Bone Spine. 2011 Mar;78(2):179-83
pubmed: 20851020
Arthritis Res Ther. 2008;10(2):R30
pubmed: 18325087
Arthritis Rheum. 2012 Jun;64(6):1828-37
pubmed: 22231638
Arthritis Rheum. 2012 Mar;64(3):617-29
pubmed: 21952978
Ann Rheum Dis. 2012 Jul;71(7):1157-62
pubmed: 22267330
Lancet. 2013 Feb 9;381(9865):451-60
pubmed: 23294500
Ann Rheum Dis. 2013 Apr;72(4):560-5
pubmed: 22589377
Arthritis Rheum. 1988 Mar;31(3):315-24
pubmed: 3358796
Arthritis Rheum. 2009 Oct;60(10):2870-9
pubmed: 19790070
Semin Arthritis Rheum. 2016 Dec;46(3):261-271
pubmed: 27443588
Ann Intern Med. 2013 Aug 20;159(4):253-61
pubmed: 24026258
Semin Arthritis Rheum. 2016 Aug;46(1):71-80
pubmed: 27079757
J Rheumatol. 2014 May;41(5):837-52
pubmed: 24692527
Ann Rheum Dis. 2016 Feb;75(2):341-7
pubmed: 25609412
Arthritis Rheumatol. 2015 Mar;67(3):616-25
pubmed: 25470338
Arthritis Rheum. 2012 Apr;64(4):970-81
pubmed: 22006202
Arthritis Care Res (Hoboken). 2011 Aug;63(8):1150-8
pubmed: 21584942
Clin Med Insights Cardiol. 2016 Mar 13;10:37-42
pubmed: 26997876
Nat Rev Rheumatol. 2013 Sep;9(9):513-23
pubmed: 23774906
Arthritis Rheum. 2013 Mar;65(3):559-70
pubmed: 23348607
J Rheumatol. 2005 Mar;32(3):435-42
pubmed: 15742434
Arthritis Rheum. 2005 Oct;52(10):3045-53
pubmed: 16200609
Arthritis Rheum. 1995 Jan;38(1):44-8
pubmed: 7818570
Rheumatology (Oxford). 2011 Mar;50(3):518-31
pubmed: 21071477
Arthritis Rheum. 2005 Mar;52(3):722-32
pubmed: 15751097
Mod Rheumatol. 2015 Jul;25(4):514-21
pubmed: 25496464
Arthritis Rheum. 2003 Jul;48(7):1833-40
pubmed: 12847676
Ann Rheum Dis. 2017 Jul;76(7):1253-1262
pubmed: 28143815