Major Adverse Cardiovascular Events Related to JAK Inhibitors: A Disproportionality Analysis Using the WHO Global Individual Case Safety Database.

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Safety Pub Date : 2025-03-23 DOI:10.1007/s40264-025-01535-8

Raffaella Di Napoli, Christophe Richez, Cristina Scavone, Allison Singier, Maxime Demorgues, Annamaria Mascolo, Annalisa Capuano, Francesco Salvo

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引用次数: 0

Abstract

Background: Rheumatoid arthritis (RA) is commonly treated with Janus kinase inhibitors (JAKis) and anti-tumor necrosis factor-α (anti-TNFα), but the cardiovascular safety profiles of these drugs remain unclear.

Objective: The aim of this study was to describe the individual case safety reports of major adverse cardiac events (MACE) or stroke and to determine whether there was a difference in the frequency of reporting of cardiovascular events between JAKis and anti-TNFα used in RA.

Methods: A case/non-case study was conducted using the WHO VigiBase^® database. Descriptive analysis was performed, the time to onset (TTO) of MACE was calculated, and the reporting odds ratio (ROR) was used to estimate the frequency of MACE reports associated with JAKis versus anti-TNFα in RA.

Results: A total of 18,099 cases of MACE were identified, of which 2543 (14%) were associated with JAKis, predominantly in women (65.4%) and in patients aged ≥65 years (49.9%). The median time to onset was 210 days (IQR 60-510) for JAKis and 690 days (210-1460) for anti-TNFα. JAKis were associated with higher odds of reporting MACE (ROR 1.38 [95% CI 1.32-1.44]), mainly due to non-fatal stroke (1.65 [1.55-1.75]). Stroke as a whole showed similar results (1.62 [1.53-1.72]). The ROR of MACE was also slightly increased in patients aged <65 years treated with JAKis (1.29 [1.21-1.39]).

Conclusions: Compared with anti-TNFα, JAKis were more associated with MACE, especially stroke, and with a shorter time to onset. These data support the hypothesis of a different cardiovascular reporting frequency between JAKis and anti-TNFα. In patients with identified cardiovascular risk, anti-TNFα should be preferred to JAKis until more definitive results are available.

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来源期刊

Drug Safety 医学-毒理学

CiteScore

7.60

自引率

7.10%

发文量

112

审稿时长

6-12 weeks

期刊介绍： Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.