Background

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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系统评价：单克隆抗体诱导的亚急性皮肤红斑狼疮。

背景

亚急性皮肤红斑狼疮 (SCLE) 缺乏一致的诊断标准，发病机制也知之甚少。单克隆抗体 (mAbs) 诱导 SCLE 的报道越来越多，但关于该疾病的病因、临床特征和自然病程的数据有限。

方法

我们与多国多专业小组合作设计了一套 SCLE 诊断标准。对于 mAb 诱导的 SCLE 病例（PROSPERO 注册协议 CRD42019116521），该系统评价采用了五个数据库的两层搜索策略。为了探讨相对 mAb 使用与报告的 SCLE 病例数之间的关系，对 2013 年至 2018 年的全球商业数据和估计的年度治疗成本对 mAb 用户的估计数量进行了建模。

结果

从 40 篇论文中，我们确定了 52 例 mAb 诱导的 SCLE，发生在女性占 73% 且中位年龄为 61 岁的队列中。50% 的病例是由抗肿瘤坏死因子 (TNF)-ɑ 药物诱导的。SCLE 发作前平均三个药物剂量，停药后病变持续平均 7 周。最常使用口服和外用皮质类固醇。根据全球销售数据，在获得许可的 mAb 中，阿达木单抗、地诺单抗、利妥昔单抗、依那西普和英夫利昔单抗的年度用户相对数量最高。将 mAb 诱导的 SCLE 病例数与估计的年使用量进行比较，检查点抑制剂派姆单抗和纳武单抗相对于其全球使用显示出惊人的高 SCLE 发生率，但伊匹单抗没有。

结论

我们提出了第一篇系统评价，从触发因素、临床症状、实验室检查结果、预后和治疗方法方面对 mAb 诱导的 SCLE 进行了表征。我们确定了与使用检查点抑制剂和抗 TNFɑ 药物相关的升高率。