胃肠道穿孔与JAK抑制剂相关:FDA不良事件报告系统的歧化分析。

IF 6.7 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
United European Gastroenterology Journal Pub Date : 2025-05-01 Epub Date: 2024-12-30 DOI:10.1002/ueg2.12736
Adam Goldman, Emanuel Raschi, Amit Druyan, Kassem Sharif, Adi Lahat, Ilan Ben-Zvi, Shomron Ben-Horin
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引用次数: 0

摘要

背景:在临床试验中使用Janus激酶(JAK)抑制剂治疗的少数类风湿性关节炎(RA)患者中有胃肠道穿孔的报道。然而,需要大规模的上市后数据库来进一步调查这种潜在的罕见但严重的不良事件。方法:对FDA不良事件报告系统(2014年7月至2023年9月)进行回顾性药物警戒研究,评估与生物疾病改善抗风湿药物(bDMARDs)相比,JAK抑制剂对RA患者胃肠道穿孔的报告。采用多变量logistic回归模型计算调整后的报告优势比(adj.ROR)。结果:在纳入研究的399,983例RA患者中,76,446例接受了JAK抑制剂(托法替尼,n = 52,365;Upadacitinib, n = 21856;baricitinib, n = 2225)和323,537人接受bDMARDs (TNF抑制剂,利妥昔单抗和阿巴接受)治疗。总体而言,发现了230例使用JAK抑制剂后胃肠道穿孔的病例,从治疗开始的中位时间为9 (IQR: 4-22)个月。与bdmard相比,JAK抑制剂与胃肠道穿孔的报告相关(adj.ROR = 1.98[1.69-2.31])。服用JAK抑制剂或bdmard的患者同时使用类固醇或非类固醇抗炎药时,胃肠道穿孔发生率增加(adr . ror = 2.82[2.41-3.31])。上消化道和下消化道穿孔均明显多报(n = 51, adj.ROR = 1.55 [1.12-2.14], n = 143, adj.ROR = 1.78[1.46-2.17])。此外,所有JAK抑制剂的安全性信号均显著:tofacitinib (n = 125, adr . ror = 1.52[1.25-1.85])、upadacitinib (n = 84, adr . ror = 2.73[2.17-3.44])和baricitinib (n = 21, adr . ror = 5.38[3.46-8.37])。结论:在这项全球药物警戒研究中,与bDMARDs相比,所有JAK抑制剂与RA患者胃肠道穿孔报告增加相关。在更多关于IBD患者的数据出现之前,还应该提倡对这一人群进行仔细的监测并提高临床医生的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gastrointestinal Perforations Associated With JAK Inhibitors: A Disproportionality Analysis of the FDA Adverse Event Reporting System.

Background: Gastrointestinal perforations have been reported in a small number of rheumatoid arthritis (RA) patients treated with Janus kinase (JAK) inhibitors in clinical trials. However, large-scale postmarketing data repositories are needed to further investigate this potentially rare but serious adverse event.

Methods: A retrospective, pharmacovigilance study of the FDA adverse event reporting system (July 2014 to September 2023) assessing the reporting of gastrointestinal perforations following JAK inhibitors compared to biological disease-modifying antirheumatic drugs (bDMARDs) in RA patients. The adjusted reporting odds ratio (adj.ROR) was calculated using a multivariable logistic regression model.

Results: Of 399,983 RA patients included in the study, 76,446 were treated with JAK inhibitors (tofacitinib, n = 52,365; upadacitinib, n = 21,856; baricitinib, n = 2225) and 323,537 were treated with bDMARDs (TNF inhibitors, rituximab, and abatacept). Overall, 230 cases of gastrointestinal perforation following JAK inhibitors were identified, with a median time of 9 (IQR: 4-22) months from treatment initiation. Compared with bDMARDs, JAK inhibitors were associated with a higher-than-expected reporting of gastrointestinal perforations (adj.ROR = 1.98[1.69-2.31]). Increased reporting of gastrointestinal perforations was observed among recipients of JAK inhibitors or bDMARDs who used steroids or non-steroidal anti-inflammatory drugs concurrently (adj.ROR = 2.82 [2.41-3.31]). Perforations of both the upper and lower gastrointestinal tract were significantly over-reported (n = 51, adj.ROR = 1.55 [1.12-2.14], n = 143, adj.ROR = 1.78 [1.46-2.17], respectively). Furthermore, the safety signal was significant across all JAK inhibitors: tofacitinib (n = 125, adj.ROR = 1.52 [1.25-1.85]), upadacitinib (n = 84, adj.ROR = 2.73 [2.17-3.44]), and baricitinib (n = 21, adj.ROR = 5.38 [3.46-8.37]).

Conclusion: In this global pharmacovigilance study, all JAK inhibitors were associated with increased reporting of gastrointestinal perforations compared with bDMARDs in RA patients. Until more data on IBD patients emerge, careful surveillance and increased clinicians' awareness should also be advocated for this population.

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来源期刊
United European Gastroenterology Journal
United European Gastroenterology Journal GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
10.50
自引率
13.30%
发文量
147
期刊介绍: United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
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