Department of Internal Medicine and Clinical Immunlogy, Sorbonne Université, Pitié-Salpêtrière University Hospital, Paris, France; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, Paris, France.
Regional Pharmacovigilance Centre, Department of Pharmacology, Sorbonne Université, INSERM CIC Paris-Est, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
J Autoimmun. 2020 Jul;111:102454. doi: 10.1016/j.jaut.2020.102454. Epub 2020 Apr 14.
Drug-induced uveitis is a rare but sight-threatening condition. We seek to determine the spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors (ICI).
Retrospective pharmacovigilance study based on adverse drug reactions reported within VigiBase, the WHO international pharmacovigilance database. We included deduplicated individual case safety reports (ICSRs) reported as 'uveitis' at Preferred Term level according to the Medical Dictionary for Drug Regulatory Activities between 1967 and 04/28/2019. We performed a case/non-case analysis to study if suspected drug-induced uveitis were differentially reported for each suspected treatment compared to the full database. We excluded drugs with potential indication bias.
1404 ICSRs corresponding to 37 drugs had a significant over-reporting signal with a median age of 57 [42-68] years and 45.7% of males. We identified five major groups of treatments: bisphosphonates (26.9%), non-antiviral anti-infectious drugs (25.4%), protein kinase inhibitors (15.5%), ICI (15.0%), and antiviral drugs (11.1%). Severe visual loss was reported in 12.1% of cases. ICI and protein kinase inhibitors were the most recently emerging signals. The time to onset between first infusion and uveitis was significantly different between groups ranging from 5 days [2-19] in the bisphosphonate group to 138.5 [47.25-263.75] in protein kinase inhibitors group (p < 0.0001). Anti-Programmed Cell death 1 represented more than 70% of ICI-induced uveitis. We identified Vogt-Koyanagi-Harada (VKH)-like syndrome as being associated with ICI use.
The spectrum of drug-induced uveitis has changed with the evolution of pharmacopeia and the recent emergence of ICIs. VKH-like syndrome has been reported with ICI and protein kinase inhibitors therapy.
药物性葡萄膜炎是一种罕见但可致盲的疾病。我们旨在确定免疫检查点抑制剂（ICI）时代药物性葡萄膜炎的范围。
这是一项基于世界卫生组织国际药物监测数据库 VigiBase 中报告的不良药物反应的回顾性药物警戒研究。我们根据药物监管活动医学词典，将 Preferred Term 水平报告为“葡萄膜炎”的经去重的个例安全报告（ICSR）纳入研究，纳入时间为 1967 年至 2019 年 4 月 28 日。我们进行了病例/非病例分析，以研究与整个数据库相比，疑似药物性葡萄膜炎是否在每种疑似治疗中报告存在差异。我们排除了具有潜在适应证偏倚的药物。
1404 份 ICSR 对应 37 种药物，信号提示存在显著超报告现象，中位年龄为 57 岁[42-68]岁，男性占 45.7%。我们确定了五类主要的治疗药物：双膦酸盐（26.9%）、非抗病毒抗感染药物（25.4%）、蛋白激酶抑制剂（15.5%）、ICI（15.0%）和抗病毒药物（11.1%）。12.1%的病例报告有严重视力丧失。ICI 和蛋白激酶抑制剂是最近出现的信号。首次输注与葡萄膜炎之间的发病时间在各组之间有显著差异，从双膦酸盐组的 5 天[2-19]到蛋白激酶抑制剂组的 138.5[47.25-263.75]（p<0.0001）。抗程序性死亡 1 代表了超过 70%的 ICI 诱导的葡萄膜炎。我们发现 Vogt-Koyanagi-Harada（VKH）样综合征与 ICI 的使用有关。
随着药物学的发展和 ICI 的出现，药物性葡萄膜炎的范围发生了变化。VKH 样综合征已在 ICI 和蛋白激酶抑制剂治疗中报告。
