Abstract：
OBJECTIVE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy.
METHODS: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration.
RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis.
CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.
METHODS: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration.
RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis.
CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.
摘要：
目的：比较接受BRAF抑制剂的皮肤黑色素瘤或肺癌患者与接受免疫检查点抑制剂（ICIs）或常规细胞毒性化疗的患者非感染性葡萄膜炎的发生率。
方法：基于全国人群的回顾性临床队列研究方法：来自韩国健康保险审查和评估服务数据库，我们回顾性定义了77,323例接受BRAF抑制剂治疗的皮肤黑色素瘤或肺癌患者（BRAF抑制剂暴露组；n=396），ICIs(ICI暴露组；n=22,474)，或常规细胞毒性化疗（未暴露组；n=54,453）。我们计算了从BRAF抑制剂的第一天开始，每组非感染性葡萄膜炎的1年累积发病率，ICI或细胞毒性剂给药。
结果：在开始治疗的第一年，葡萄膜炎的累计发病率为0.33%,0.35%,和2.27%的未暴露，ICI暴露，和BRAF抑制剂暴露组，分别。调整后的风险比（aHR）表明，与未暴露和ICI暴露组相比，BRAF抑制剂暴露组葡萄膜炎的风险增加了7.52倍和5.68倍（95％置信区间[CI]3.83-14.75，P<0.001和95％CI2.81-11.47，P<0.001）。1:4倾向得分匹配后，aHR显示葡萄膜炎和严重葡萄膜炎的风险增加35.51倍和15.80倍（95％CI4.49-280.48，P=0.001和95％CI1.76-141.00，P=0.014），分别,在BRAF抑制剂暴露与未暴露的患者中。BRAF抑制剂暴露组的交叉分析显示，与指数前1年相比，指数后1年葡萄膜炎风险增加了3.71倍（95％CI1.03-13.40，P=0.046）。在BRAF抑制剂暴露组中，女性性别,慢性肾病,黑色素瘤与增加的趋势有关，尽管不重要，葡萄膜炎的风险。
结论：接受BRAF抑制剂治疗的黑色素瘤或肺癌患者与非感染性葡萄膜炎的风险显著高于接受常规细胞毒性药物或ICIs治疗的患者。这些发现强调了预处理患者教育对BRAF抑制剂相关葡萄膜炎风险的重要性，以便在给药期间出现症状时能够及时进行眼科评估和治疗。
方法：基于全国人群的回顾性临床队列研究方法：来自韩国健康保险审查和评估服务数据库，我们回顾性定义了77,323例接受BRAF抑制剂治疗的皮肤黑色素瘤或肺癌患者（BRAF抑制剂暴露组；n=396），ICIs(ICI暴露组；n=22,474)，或常规细胞毒性化疗（未暴露组；n=54,453）。我们计算了从BRAF抑制剂的第一天开始，每组非感染性葡萄膜炎的1年累积发病率，ICI或细胞毒性剂给药。
结果：在开始治疗的第一年，葡萄膜炎的累计发病率为0.33%,0.35%,和2.27%的未暴露，ICI暴露，和BRAF抑制剂暴露组，分别。调整后的风险比（aHR）表明，与未暴露和ICI暴露组相比，BRAF抑制剂暴露组葡萄膜炎的风险增加了7.52倍和5.68倍（95％置信区间[CI]3.83-14.75，P<0.001和95％CI2.81-11.47，P<0.001）。1:4倾向得分匹配后，aHR显示葡萄膜炎和严重葡萄膜炎的风险增加35.51倍和15.80倍（95％CI4.49-280.48，P=0.001和95％CI1.76-141.00，P=0.014），分别,在BRAF抑制剂暴露与未暴露的患者中。BRAF抑制剂暴露组的交叉分析显示，与指数前1年相比，指数后1年葡萄膜炎风险增加了3.71倍（95％CI1.03-13.40，P=0.046）。在BRAF抑制剂暴露组中，女性性别,慢性肾病,黑色素瘤与增加的趋势有关，尽管不重要，葡萄膜炎的风险。
结论：接受BRAF抑制剂治疗的黑色素瘤或肺癌患者与非感染性葡萄膜炎的风险显著高于接受常规细胞毒性药物或ICIs治疗的患者。这些发现强调了预处理患者教育对BRAF抑制剂相关葡萄膜炎风险的重要性，以便在给药期间出现症状时能够及时进行眼科评估和治疗。
