与皮下注射生物性改善病情抗风湿药相比，JAK抑制剂托法替布和巴瑞替尼的感染风险更高。
Higher infection risk for JAK inhibitors tofacitinib and baricitinib compared to subcutaneous biological DMARDs.
作者信息
Opdam M A A, Broeder N den, van den Bemt B J F, Mulder K, van de Wiel K M, van Ballegooijen H, van Crevel R, den Broeder A A
机构信息
Department of Rheumatology, Sint Maartenskliniek, Antwoordnummer 2237, 6500 WC, Nijmegen, The Netherlands.
Department of Pharmacy, Sint Maartenskliniek, Ubbergen, The Netherlands.
出版信息
Clin Rheumatol. 2024 Jun;43(6):2133-2138. doi: 10.1007/s10067-024-06980-x. Epub 2024 May 4.
INTRODUCTION
Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce.
METHODS
From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years.
RESULTS
In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups.
CONCLUSION
In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib.
引言
类风湿性关节炎（RA）通常使用改善病情抗风湿药（DMARDs）进行治疗，包括生物DMARDs（bDMARDs），以及最近的 Janus 激酶抑制剂（JAKi）。随机试验表明 JAKi 和 bDMARDs 的感染风险相似，但实际数据较少。
方法
从一个具有全国代表性的处方数据库中，纳入了在 2018 年 8 月 1 日至 2021 年 1 月 31 日期间开始使用新的 JAKi 或 bDMARDs 的成年 RA 患者。抗生素、抗病毒或抗真菌药物的处方被用作感染的替代指标。比较了 JAKi 和 bDMARDs 之间的感染发病率（IR），并使用多水平泊松回归估计感染风险，该回归对随访时间和潜在混杂因素进行了调整，并按年龄<65 岁和≥65 岁进行了分层。
结果
在 14989 名患者中，我们确定了 20050 次使用 JAKi 或 bDMARDs 的治疗疗程。与 bDMARDs（35/100 患者年，调整发病率比（IRR）1.22，95%CI 1.12 - 1.33）相比，JAKi 的感染 IR 显著更高（48/100 患者年）。与 bDMARDs 相比，JAKi 中带状疱疹感染更多（调整 IRR 2.65，95%CI 1.94 - 3.60）。比较 JAKi 巴瑞替尼和托法替布时，未发现感染 IR 有显著差异。在老年患者中，感染 IR 更高，但各年龄组之间的 IRR 相似。
结论
与 bDMARDs相比，JAKi 与略高的感染风险相关，尤其是带状疱疹风险更高。在老年患者中，感染 IR 更高，但 JAKi 和 bDMARDs 的感染风险相似。未发现托法替布和巴瑞替尼在感染风险上有差异。要点 • 与 bDMARDs 相比，JAKi 在所有年龄段都与略高的感染风险相关 • 证实使用 JAK 抑制剂的患者带状疱疹风险增加 • 托法替布和巴瑞替尼之间的感染发病率无显著差异。
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