Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials

被引：152

作者：

Xie, Wenhui ^{[1
]}

Huang, Yanrong ^{[1
]}

Xiao, Shiyu ^{[2
]}

Sun, Xiaoying ^{[1
]}

Fan, Yong ^{[1
]}

Zhang, Zhuoli ^{[1
]}

机构：

[1] Peking Univ, Hosp 1, Dept Rheumatol & Clin Immunol, Beijing 100006, Peoples R China

[2] Peking Univ, Hosp 3, Dept Gastroenterol, Beijing, Peoples R China

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2019年 / 78卷 / 08期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

SELECTIVE JAK1 INHIBITOR; MODIFYING ANTIRHEUMATIC DRUG; NECROSIS-FACTOR INHIBITORS; INADEQUATE RESPONSE; DOUBLE-BLIND; TOFACITINIB CP-690,550; PHASE IIB; JAPANESE PATIENTS; BACKGROUND METHOTREXATE; VX-509; DECERNOTINIB;

D O I：

10.1136/annrheumdis-2018-214846

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives To investigate the effect of Janus kinase inhibitors (Jakinibs) on cardiovascular risk in adult patients with rheumatoid arthritis (RA) via a meta-analysis of randomised controlled trials (RCTs). Methods PubMed, Embase and Cochrane library were thoroughly searched for RCTs reporting safety issues in patients with RA receiving Jakinibs, from inception to October 2018. The primary and secondary outcomes were all cardiovascular events (CVEs) and major adverse cardiovascular events (MACEs)/venous thromboembolism events (VTEs). OR and 95% CI were calculated using the Mantel-Haenszel fixed-effect method. Results 26 RCTs randomising 11 799 patients were included. No significant difference was observed regarding all CVEs risk following Jakinibs usage in general (OR 1.04 (0.61 to 1.76), p = 0.89), tofacitinib (OR 0.63 (0.26 to 1.54), p = 0.31), baricitinib (OR 1.21 (0.51 to 2.83), p = 0.66), upadacitinib (OR 3.29 (0.59 to 18.44), p = 0.18), peficitinib (OR 0.43 (0.07 to 2.54), p = 0.35) or decernotinib (OR 1.12 (0.13 to 10.11), p = 0.92). Likewise, there was no significant difference for Jakinibs treatment overall regarding occurrence of MACEs (OR 0.80 (0.36 to 1.75), p = 0.57) or VTEs (OR 1.16 (0.48 to 2.81), p = 0.74). Dose-dependent impact of Jakinibs on the risks of all CVEs, MACEs and VTEs was not observed in tofacitinib (5 mg vs 10 mg), upadacitinib (15 mg vs 30 mg), whereas baricitinib at 2 mg was found to be safer than 4 mg in all CVEs incidence (OR 0.19 (0.04 to 0.88), p = 0.03). Conclusion The existing evidence from RCTs indicated no significant change in cardiovascular risk for Jakinib-treated patients with RA in a short-term perspective, but postmarketing data are sorely needed to ascertain their cardiovascular safety, especially at the higher dose, due to increased risk of thromboembolism events for both tofacitinib and baricitinib at higher dosage.

引用

页码：1048 / 1054

页数：7

共 64 条

[31] Peficitinib, a JAK Inhibitor, in the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate [J].

Kivitz, A. J. ;

Gutierrez-Urena, S. R. ;

Poiley, J. ;

Genovese, M. C. ;

Kristy, R. ;

Shay, K. ;

Wang, X. ;

Garg, J. P. ;

Zubrzycka-Sienkiewicz, A. .

ARTHRITIS & RHEUMATOLOGY, 2017, 69 (04) :709-719

[32] Tofacitinib in Combination With Nonbiologic Disease-Modifying Antirheumatic Drugs in Patients With Active Rheumatoid Arthritis A Randomized Trial [J].

Kremer, Joel ;

Li, Zhan-Guo ;

Hall, Stephen ;

Fleischmann, Roy ;

Genovese, Mark ;

Martin-Mola, Emilio ;

Isaacs, John D. ;

Gruben, David ;

Wallenstein, Gene ;

Krishnaswami, Sriram ;

Zwillich, Samuel H. ;

Koncz, Tamas ;

Riese, Richard ;

Bradley, John .

ANNALS OF INTERNAL MEDICINE, 2013, 159 (04) :253-+

[33] Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase IIb Study of Patients With Active Rheumatoid Arthritis [J].

Kremer, Joel M. ;

Genovese, Mark C. ;

Keystone, Edward ;

Taylor, Peter C. ;

Zuckerman, Steven H. ;

Ruotolo, Giacomo ;

Schlichting, Douglas E. ;

Crotzer, Victoria L. ;

Nantz, Eric ;

Beattie, Scott D. ;

Macias, William L. .

ARTHRITIS & RHEUMATOLOGY, 2017, 69 (05) :943-952

[34] A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy [J].

Kremer, Joel M. ;

Emery, Paul ;

Camp, Heidi S. ;

Friedman, Alan ;

Wang, Li ;

Othman, Ahmed A. ;

Khan, Nasser ;

Pangan, Aileen L. ;

Jungerwirth, Steven ;

Keystone, Edward C. .

ARTHRITIS & RHEUMATOLOGY, 2016, 68 (12) :2867-2877

[35] A Phase IIb Dose-Ranging Study of the Oral JAK Inhibitor Tofacitinib (CP-690,550) Versus Placebo in Combination With Background Methotrexate in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate Alone [J].

Kremer, Joel M. ;

Cohen, Stanley ;

Wilkinson, Bethanie E. ;

Connell, Carol A. ;

French, Jonathan L. ;

Gomez-Reino, Juan ;

Gruben, David ;

Kanik, Keith S. ;

Krishnaswami, Sriram ;

Pascual-Ramos, Virginia ;

Wallenstein, Gene ;

Zwillich, Samuel H. .

ARTHRITIS AND RHEUMATISM, 2012, 64 (04) :970-981

[36] The Safety and Efficacy of a JAK Inhibitor in Patients With Active Rheumatoid Arthritis Results of a Double-Blind, Placebo-Controlled Phase IIa Trial of Three Dosage Levels of CP-690,550 Versus Placebo [J].

Kremer, Joel M. ;

Bloom, Bradley J. ;

Breedveld, Ferdinand C. ;

Coombs, John H. ;

Fletcher, Mark P. ;

Gruben, David ;

Krishnaswami, Sriram ;

Burgos-Vargas, Ruben ;

Wilkinson, Bethanie ;

Zerbini, Cristiano A. F. ;

Zwillich, Samuel H. .

ARTHRITIS AND RHEUMATISM, 2009, 60 (07) :1895-1905

[37] Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study [J].

Kume, Kensuke ;

Amano, Kanzo ;

Yamada, Susumu ;

Kanazawa, Toshikatsu ;

Ohta, Hiroyuki ;

Hatta, Kazuhiko ;

Amano, Kuniki ;

Kuwaba, Noriko .

RHEUMATOLOGY INTERNATIONAL, 2017, 37 (12) :2079-2085

[38] Tofacitinib versus Methotrexate in Rheumatoid Arthritis [J].

Lee, Eun Bong ;

Fleischmann, Roy ;

Hall, Stephen ;

Wilkinson, Bethanie ;

Bradley, John D. ;

Gruben, David ;

Koncz, Tamas ;

Krishnaswami, Sriram ;

Wallenstein, Gene V. ;

Zang, Chuanbo ;

Zwillich, Samuel H. ;

van Vollenhoven, Ronald F. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (25) :2377-2386

[39] Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies [J].

Li, Ling ;

Shen, Jiantong ;

Bala, Malgorzata M. ;

Busse, Jason W. ;

Ebrahim, Shanil ;

Vandvik, Per Olav ;

Rios, Lorena P. ;

Malaga, German ;

Wong, Evelyn ;

Sohani, Zahra ;

Guyatt, Gordon H. ;

Sun, Xin .

BMJ-BRITISH MEDICAL JOURNAL, 2014, 348

[40] The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study [J].

Lindhardsen, Jesper ;

Ahlehoff, Ole ;

Gislason, Gunnar Hilmar ;

Madsen, Ole Rintek ;

Olesen, Jonas Bjerring ;

Torp-Pedersen, Christian ;

Hansen, Peter Riis .

ANNALS OF THE RHEUMATIC DISEASES, 2011, 70 (06) :929-934

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