Department of Rheumatology and Clinical Immunology, Peking University First Hospital, No.8, Xishiku Street, West District, Beijing 100034, China.
Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China.
Autoimmun Rev. 2020 Dec;19(12):102687. doi: 10.1016/j.autrev.2020.102687. Epub 2020 Oct 22.
Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs), but patients with preexisting autoimmune disease (PAD) have been excluded from clinical trials, leaving serious gaps in knowledge.
To evaluate the safety and efficacy of ICIs in PAD patients and cancer and explore the impact of different PAD types and baseline receiving immunosuppressive therapy.
Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through August 2019 for observational studies reporting safety and efficacy data among ICI-treated patients with cancer and PAD.
619 ICI-treated patients with PAD in 14 publications were finally identified. In the random-effects meta-analysis, pooled incidence of PAD flares, de novo immune-related adverse events (irAEs) or both of any grade was 60% (95%CI = 52%-68%). Separately, there were 219 and 206 patients experiencing PAD exacerbation and de novo irAEs of any grade, yielding a pooled incidence of 35% (95%CI = 29%-41%) and 33% (95%CI = 24%-42%) respectively. Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR = 1.25-1.88). A total of 136 patients showed complete or partial response, corresponding to a pooled response rates of 30% (95%CI = 22%-39%). There were no statistical differences between patients with and without immunosuppressive therapy at ICI start regarding flare (RR = 1.08, 95%CI = 0.72-1.62), but a trend toward lower response rates was observed in patients with baseline immunosuppressants (RR = 0.58, 95%CI = 0.26-1.33).
Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. ICI treatment are also effective in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.
免疫检查点抑制剂（ICIs）常与免疫相关不良事件（irAEs）相关，但患有自身免疫性疾病（PAD）的患者已被排除在临床试验之外，导致知识严重缺失。
评估 ICIs 在 PAD 患者和癌症中的安全性和疗效，并探讨不同 PAD 类型和基线接受免疫抑制治疗的影响。
系统检索了 PubMed、EMBASE 和 Cochrane 图书馆从成立到 2019 年 8 月期间发表的观察性研究报告，这些研究报告了接受 ICI 治疗的癌症和 PAD 患者的安全性和疗效数据。
最终在 14 篇文献中确定了 619 例接受 ICI 治疗的 PAD 患者。在随机效应荟萃分析中，任何等级的 PAD 发作、新发免疫相关不良事件（irAEs）或两者均的累积发生率为 60%（95%CI=52%-68%）。另外，有 219 例和 206 例患者分别出现 PAD 加重和任何等级的新发 irAEs，累积发生率分别为 35%（95%CI=29%-41%）和 33%（95%CI=24%-42%）。与其他 PAD 相比，类风湿关节炎与发作发生率较高呈趋势相关（RR=1.25-1.88）。共有 136 例患者表现出完全或部分缓解，总体缓解率为 30%（95%CI=22%-39%）。在开始使用 ICI 时，是否使用免疫抑制剂治疗对发作（RR=1.08，95%CI=0.72-1.62）无统计学差异，但在基线使用免疫抑制剂的患者中，缓解率呈下降趋势（RR=0.58，95%CI=0.26-1.33）。
ICI 治疗的 PAD 患者中经常出现免疫毒性，但通常是轻微的，并且无需停止治疗即可控制。ICI 治疗在 PAD 患者中也是有效的，但应考虑密切监测和多学科合作，特别是对于同时接受免疫抑制剂治疗或患有类风湿关节炎的患者。
Zotero 插件