Isufi Daniel, Jensen Mikkel Bak, Loft Nikolai, Skov Lone, Elberling Jesper, Alinaghi Farzad
Department of Dermatology and Allergy, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
National Allergy Research Centre, Department of Dermatology and Allergy, University of Copenhagen, Hellerup, Denmark.
JAAD Int. 2024 Nov 2;18:106-116. doi: 10.1016/j.jdin.2024.09.012. eCollection 2025 Feb.
Janus kinase (JAK) inhibitors block pathways involved in inflammation and immune response, making JAK inhibitors useful in the treatment of various diseases. While the efficacy of these drugs has been proven in several studies, their safety profile needs to be further investigated. In this systematic review and meta-analysis, we examined the risk of infections during treatment with oral JAK inhibitors with no concomitant treatment compared to placebo in phase 2 and 3 randomized, placebo-controlled trials. The medical databases PubMed, Web of Science, and EMBASE were searched from inception through February 2024, yielding 13,567 nonduplicate articles, of which 69 were included in the final quantitative analysis. Overall, we found that treatment with oral JAK inhibitors was associated with an increased risk of infections compared to placebo across all indications (relative risk: 1.39 [95% CI: 1.096-1.76, = .0067]) and in dermatologic indications (relative risk: 1.46 [95% CI, 1.10-1.93, = .0097]). Remarkably, an increased risk of herpes zoster infections was found in dermatologic indications but not in nondermatologic indications. In conclusion, we identified a significantly increased risk of developing infections during treatment with oral JAK inhibitors compared to placebo across indications. In sub-analyses, we additionally found an increased risk of herpes zoster in dermatologic indications.
Janus激酶（JAK）抑制剂可阻断参与炎症和免疫反应的信号通路，因此JAK抑制剂可用于治疗多种疾病。虽然这些药物的疗效已在多项研究中得到证实，但其安全性仍需进一步研究。在这项系统评价和荟萃分析中，我们在2期和3期随机、安慰剂对照试验中，比较了口服JAK抑制剂在无联合治疗时与安慰剂相比的感染风险。检索了医学数据库PubMed、Web of Science和EMBASE，时间跨度从建库至2024年2月，共获得13567篇不重复文章，其中69篇纳入最终定量分析。总体而言，我们发现，在所有适应症中，口服JAK抑制剂治疗与安慰剂相比感染风险增加（相对风险：1.39 [95%CI：1.096 - 1.76，P = 0.0067]），在皮肤科适应症中也是如此（相对风险：1.46 [95%CI，1.10 - 1.93，P = 0.0097]）。值得注意的是，在皮肤科适应症中发现带状疱疹感染风险增加，而在非皮肤科适应症中未发现。总之，我们发现与安慰剂相比，口服JAK抑制剂治疗期间发生感染的风险显著增加。在亚组分析中，我们还发现皮肤科适应症中带状疱疹风险增加。
