University College London, University College London Hospitals NHS Foundation Trust, London, UK.
Medical Sciences Division, University of Oxford, Oxford, UK.
Drugs R D. 2020 Dec;20(4):319-330. doi: 10.1007/s40268-020-00320-5.
Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease.
We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs.
From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not.
We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents.
亚急性皮肤型狼疮(SCLE)缺乏共识性诊断标准,其发病机制尚不清楚。越来越多的报道表明单克隆抗体(mAbs)可诱导 SCLE,但关于该病的病因、临床特征和自然病程的数据有限。
我们与一个多国家、多专科的专家小组合作制定了一套 SCLE 诊断标准。本系统评价采用了两层搜索策略,在五个数据库中搜索 mAb 诱导的 SCLE 病例(PROSPERO 注册的方案 CRD42019116521)。为了探讨相对 mAb 使用与报告的 SCLE 病例数量之间的关系,我们根据 2013 年至 2018 年全球商业数据和估计的年度治疗费用,对 mAb 使用人数进行建模。
从 40 篇论文中,我们确定了 52 例 mAb 诱导的 SCLE 病例,发生在女性占 73%、中位年龄 61 岁的队列中。50%的病例是由抗肿瘤坏死因子(TNF)-ɑ 药物引起的。SCLE 发病前中位数使用了三种药物剂量,停药后皮损中位持续 7 周。最常使用的药物是口服和局部皮质类固醇。在已上市的 mAbs 中,根据全球销售数据,阿达木单抗、地舒单抗、利妥昔单抗、依那西普和英夫利昔单抗的年使用相对人数最高。将 mAb 诱导的 SCLE 病例数量与估计的年使用人数进行比较,检查点抑制剂 pembrolizumab 和 nivolumab 相对于其全球使用量,显示出 SCLE 发生率极高,但 ipilimumab 则没有。
我们首次系统评价了 mAb 诱导的 SCLE 与触发因素、临床特征、实验室发现、预后和治疗方法的关系。我们发现,与检查点抑制剂和抗 TNFɑ 药物的使用相关的发病率较高。