| アブストラクト | OBJECTIVES: The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited. METHODS: A retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model. RESULTS: We identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(+/-12) and 59.0(+/-13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97-2.25)], stroke [n = 973, adj.ROR=1.25 (1.16-1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13-1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17-1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00-1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged</=65 years. CONCLUSION: In this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect. |
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| ジャーナル名 | Seminars in arthritis and rheumatism |
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| 投稿日 | 2024/5/22 |
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| 投稿者 | Goldman, Adam; Galper, Bat-El Lugassy; Druyan, Amit; Grossman, Chagai; Sharif, Kassem; Shechtman, Liran; Moshkovits, Yonatan; Lahat, Adi; Ben-Zvi, Ilan |
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| 組織名 | Department of Internal Medicine F, Sheba Medical Center, Ramat-Gan, Israel;;Department of Epidemiology and Preventive Medicine, School of Public Health,;Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Sheba;Talpiot Medical Leadership Program, Sheba Medical Center, Ramat-Gan, Israel.;Department of Internal Medicine F, Sheba Medical Center, Ramat-Gan, Israel.;School of Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Tel‑Aviv,;Israel.;Israel; Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel.;Department of Critical Care Medicine, Sunnybrook Hospital, Toronto, Canada;;Department of Medicine, University of Toronto, Toronto, Canada.;Department of Internal Medicine F, Sheba Medical Center, Ramat-Gan, Israel; The;Sheba Talpiot Medical Leadership Program, Sheba Medical Center, Ramat-Gan,;Israel; School of Medicine, Sackler Faculty of Medicine, Tel-Aviv University,;Tel‑Aviv, Israel. Electronic address: Ilan.BenZvi@sheba.health.gov.il. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38772185/ |
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