Safety of JAK inhibitors: focus on cardiovascular and thromboembolic events

ABSTRACT

Introduction

To date, four Janus kinase inhibitors (JAKis) are licensed for the treatment of rheumatoid arthritis (RA) and/or psoriatic arthritis (PsA) in North America and/or Europe: tofacitinib, baricitinib, upadacitinib, and filgotinib. Most DMARDs have cardioprotective potential, yet for some of them, including JAKi, the modulatory effect on cardiovascular risk remains undetermined. Since their commercialization, the risk of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is taking on a relevant role in RA patients.

Areas covered

In this article, we will review the effect of JAKi on CV risk and atherosclerosis process as major contributor to MACE. Furthermore, we will present the effect of JAKi on thromboembolic risk.

Expert opinion

Although the effect of JAKi on CV and thrombosis is one of the most relevant topic regarding RA patients, it is necessary to underline that these patients have an increased risk of these comorbidities due to the inflammation process, and further study are needed in order to understand the real role of JAKi in controlling or inducing these complications.

KEYWORDS:

• JAKi
• cardiovascular risk
• thromboembolism
• tsDMARDs
• trombosis

Article highlights

• JAKi are a new class of drugs with efficacy and safety profile used for treating patients with rheumatic inflammatory disease.

• These drugs are associated to increased risk of thromboembolic effects, although these patients have an increased risk per se due to the inflammatory process.

• The effect of these drugs on CV risk is protective, as have been shown for other DMARDs.

Reviewer disclosures

One peer reviewer has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate and the National Psoriasis Foundation. They are also the founder and majority owner of www.DrScore.com [drscore.com] and founder and part owner of Causa Research. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Declaration of interest

F Atzeni has received fees from AbbVie, Eli Lilly, Janssen, Bristol-Myers Squibb, Novartis, and research funding from Novartis, Pfizer, and Sanofi. C Popa has received consulting fees from Eli Lilly, and research funding from Novartis. M Nurmohamed has received consulting feeds from AbbVie, Celgene, Celltrion, Eli Lilly, Janssen, and Sanofi, and speaker’s fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Roche, and Sanofi, and research funding from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Grunenthal, Mundipharma, Novartis, Pfizer, Roche, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Authors’ contributions

F Atzeni, C Popa, V Nucera, M Nurmohamed participated in the literature search and the summary of all articles. All of the authors drafted the manuscript, which was critically reviewed by F Atzeni, M Nurmohamed and C Popa. All of the authors read and approved the final manuscript.

Additional information

Funding

This paper was not funded.