■免疫相关表皮坏死松解症(irEN),包括史蒂文斯-约翰逊综合征(SJS)和中毒性表皮坏死松解症(TEN),代表对免疫检查点抑制剂的潜在致死反应。最佳治疗策略仍未定义。这项研究评估了糖皮质激素和肿瘤坏死因子抑制剂(TNFi)联合治疗irEN患者的有效性和安全性。
■在这个单中心,prospective,观察性研究,患有irEN的患者接受了皮质类固醇单一疗法或皮质类固醇和TNFi的联合疗法(SJS的依那西普,英夫利昔单抗用于TEN)。主要终点是上皮再形成时间,次要终点包括皮质类固醇暴露,主要不良事件发生率,急性死亡率,和指示疾病活动和预后的生物标志物。该研究在中国临床试验注册中心(ChiCTR2100051052)注册。
■纳入了32例患者(21SJS,11TEN);14人接受联合治疗,18人接受皮质类固醇单药治疗。IrEN通常发生在ICI给药1个周期后,中位潜伏期为16天。尽管组合组中SCORTEN得分较高(3vs.2,p=0.008),这些患者经历了更快的上皮再形成(14vs.21天;p<0.001),较短的皮质类固醇治疗持续时间(22vs.32天;p=0.005),和较低的泼尼松累积剂量(1177毫克vs.1594毫克;p=0.073)。两组间主要不良事件发生率相似。3例因肺部感染或弥散性血管内凝血死亡,两组的死亡率均低于预期。死亡率增加的潜在危险因素包括淋巴细胞亚群计数持续减少(CD4+T细胞,CD8+T细胞,自然杀伤细胞)和炎症标志物(血清铁蛋白,白细胞介素-6,TNF-α)。再上皮化时间与体重指数呈负相关,与表皮脱离面积、血清白细胞介素-6和TNF-α水平呈正相关。
■皮质类固醇联合TNFi显著促进上皮再形成,减少皮质类固醇的使用,并在不增加主要不良事件的情况下降低了患者的急性死亡率,提供优于皮质类固醇单一疗法的替代方案。炎症标志物和淋巴细胞亚群对评估疾病活动性和预后具有重要价值。
UNASSIGNED: Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients.
UNASSIGNED: In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052).
UNASSIGNED: Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α.
UNASSIGNED: Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.