类风湿性关节炎

FDA 发布警告称托法替尼和其他 JAK 抑制剂可增加严重心血管事件、恶性肿瘤、血栓形成和死亡风险

美国食品药品监督管理局（Food and Drug Administration, FDA）发出警告，称托法替布和其他两种 Janus 激酶（Janus kinase, JAK）抑制剂（巴瑞替尼和 upadacitinib）将使得严重心血管事件、恶性肿瘤、血栓形成和死亡风险升高。[47]Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Sep 2021 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

这是根据一项大型随机安全性临床试验的最终结果做出，该试验将托法替布与肿瘤坏死因子（tumour necrosis factor, TNF）-α 抑制剂在类风湿性关节炎患者中进行比较。研究发现，较低剂量的托法替布（5 mg，每日两次）可升高血栓和死亡风险；在初步分析中，这种严重事件以前仅在较高剂量（10 mg，每日两次）下见诸报道。[48]ClinicalTrials.gov. Safety study of tofacitinib versus tumor necrosis factor (TNF) inhibitor in subjects with rheumatoid arthritis (A3921133). NCT02092467. Aug 2021 [internet publication]. https://clinicaltrials.gov/ct2/show/NCT02092467

FDA 建议临床医生：[47]Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Sep 2021 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death

• 将托法替布、巴瑞替尼和 upadacitinib 用于对一种或多种 TNF-α 抑制剂反应不足或无法耐受的患者

• 决定给药或继续使用此类药物进行治疗时，需考虑患者个体获益-风险状况，特别是对目前或过去吸烟的患者、有其他心血管危险因素的患者、生成恶性肿瘤的患者以及已知罹患恶性肿瘤的患者（成功治疗的非黑色素瘤皮肤癌除外）。

另外两种 JAK 抑制剂芦可替尼和 fedratinib 不适用于治疗关节炎和其他炎性疾病，因此不受该警告影响。

根据同一研究所获的结果，欧洲药品管理局（European Medicines Agency, EMA）和英国药品和医疗产品监管署（Medicines and Healthcare products Regulatory Agency, MHRA）对托法替布发布了类似的安全警报。EMA 的建议适用于年龄 >65 岁的患者、当前或过去的吸烟者、具有其他心血管危险因素的患者，以及具有其他恶性肿瘤危险因素的患者。此类患者群体中，如果没有合适的治疗替代方案，托法替布应仅用于中重度溃疡性结肠炎治疗。[48]ClinicalTrials.gov. Safety study of tofacitinib versus tumor necrosis factor (TNF) inhibitor in subjects with rheumatoid arthritis (A3921133). NCT02092467. Aug 2021 [internet publication]. https://clinicaltrials.gov/ct2/show/NCT02092467 [49]European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 7-10 June 2021. Jun 2021 [internet publication]. https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-7-10-june-2021 [50]Medicines and Healthcare products Regulatory Agency. Tofacitinib (Xeljanz): new measures to minimise risk of major adverse cardiovascular events and malignancies. Oct 2021 [internet publication]. https://www.gov.uk/drug-safety-update/tofacitinib-xeljanzv-new-measures-to-minimise-risk-of-major-adverse-cardiovascular-events-and-malignancies

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