Rheumatology Unit, Azienda Ospedaliera San Camillo - Forlanini, Rome, Italy.
Rheumatology Institute, University of Siena, Italy.
Autoimmun Rev. 2019 Aug;18(8):805-813. doi: 10.1016/j.autrev.2019.06.005. Epub 2019 Jun 7.
Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Immune checkpoint inhibitors (ICPIs) are new cancer drugs that target self-tolerance pathways exploited by tumors to escape immune destruction, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand (PD-L1). Several ICPIs have been approved by Food and Drug Administration, increasing overall survival with different cancers. However, their use can determine development of many different inflammatory side effects, that are defined immune-related adverse effects (irAEs); among others, rheumatological irAEs can develop in these patients. Currently, we have limited data about these adverse effects; particularly, few evidence come from clinical trials about patients with pre-existing autoimmune diseases because they were excluded from them. Therefore we analysed the existing scientific literature dealing with this issue, in order to answer to different clinical questions. According to all reviewed data, rheumatological irAEs are not infrequent, in both previously diseased and undiseased patients, but they are often mild and reversible. Close monitoring and interdisciplinary management and monitoring is necessary in order to ensure best care. Many questions remain unanswered or not completely answered; further data are necessary to implement our knowledge in this field and to standardize and optimize clinical practice.
免疫检查点是免疫细胞表达的小分子，在维持免疫稳态方面发挥着关键作用。免疫检查点抑制剂（ICPI）是针对肿瘤利用自身耐受途径逃避免疫破坏的新型癌症药物，如细胞毒性 T 淋巴细胞抗原 4（CTLA-4）和程序性细胞死亡 1（PD-1）或其配体（PD-L1）。几种免疫检查点抑制剂已被美国食品和药物管理局（FDA）批准，不同癌症的总生存率有所提高。然而，它们的使用可能会导致许多不同的炎症副作用，即免疫相关不良反应（irAEs）；其中，风湿性 irAEs 可能在这些患者中发生。目前，我们对这些不良反应的数据有限；特别是，由于这些患者被排除在临床试验之外，因此很少有关于患有自身免疫性疾病的患者的临床试验证据。因此，我们分析了处理这个问题的现有科学文献，以回答不同的临床问题。根据所有审查的数据，风湿性 irAEs 在既往患病和未患病患者中都不罕见，但通常是轻微和可逆的。需要密切监测和多学科管理和监测，以确保提供最佳护理。仍有许多问题未得到解答或未得到完全解答；需要进一步的数据来增强我们在这一领域的知识，并规范和优化临床实践。
