Rheumatology Department, Hospital of Prato , Prato, Italy.
Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa , Pisa, Italy.
Expert Opin Drug Saf. 2020 Jul;19(7):861-872. doi: 10.1080/14740338.2020.1774550. Epub 2020 Jun 17.
Janus kinases inhibitors (anti-JAKs), including tofacitinib, baricitinib, upadacitinib, and filgotinib, represent a new class of synthetic targeted drugs for the treatment of rheumatoid arthritis (RA). In this review, the risk of active tuberculosis (TB) occurrence in patients receiving anti-JAKs was assessed. The literature on this topic, updated to 29 February 2020 was reviewed. Overall, 40 reports (22 tofacitinib, 10 baricitinib, 5 upadacitinib, 3 filgotinib) were examined. A low frequency, not exceeding 0.25%, of active TB cases in patients were exposed to anti-JAKs. Only 1 of 89 recorded cases in tofactinib and baricitinib exposure occurred in countries at intermediate or high TB risk, and most of the cases probably were due to first mycobacterium tuberculosis (Mtb) exposure. Although no cases were observed in patients receiving upadacitinib and filgotinib, long-term trials and data from real-life are required to more precisely address the TB risk associated with the two drugs.
Discussion on the TB risk associated with anti-JAKs, and on the need for accurate evaluation of host-related risk factors in high risk countries.
Available data on anti-JAKs suggest a negligible risk of active TB occurrence in low endemic areas.
Janus 激酶抑制剂(抗-JAK 药物),包括托法替布、巴瑞替尼、乌帕替尼和菲戈替尼,代表了一类新型的用于治疗类风湿关节炎(RA)的合成靶向药物。在这篇综述中,评估了接受抗-JAK 药物治疗的患者发生活动性结核病(TB)的风险。截至 2020 年 2 月 29 日,对这一主题的文献进行了回顾。总的来说,检查了 40 份报告(22 份托法替布、10 份巴瑞替尼、5 份乌帕替尼、3 份菲戈替尼)。接受抗-JAK 药物治疗的患者中,活动性 TB 病例的频率较低,不超过 0.25%。在托法替布和巴瑞替尼暴露的 89 例记录病例中,只有 1 例发生在中或高 TB 风险国家,且大多数病例可能是由于首次接触结核分枝杆菌(Mtb)。尽管在接受乌帕替尼和菲戈替尼治疗的患者中未观察到病例,但需要长期试验和真实数据来更准确地评估这两种药物与 TB 风险的关联。
讨论抗-JAK 药物相关的 TB 风险,以及在高风险国家需要准确评估宿主相关风险因素的必要性。
关于抗-JAK 药物的数据表明,在低流行地区,活动性 TB 发生的风险可以忽略不计。