Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment
Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment
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DOI：
10.1136/annrheumdis-2017-211216
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发表时间：
2017-10-01
影响因子：
27.4
通讯作者：
Mariette, Xavier
中科院分区：
文献类型：
--
作者：
Belkhir, Rakiba;Le Burel, Sebastien;Mariette, Xavier
目的 靶向细胞毒性 T 淋巴细胞相关蛋白 4 和程序性细胞死亡蛋白 1 (PD-1) 的免疫检查点抑制剂 (ICIs) 已被证明可以改善多种癌症的生存率。然而，这些新药类别导致免疫相关不良事件 (IrAE) 增加。风湿性 IrAE 尚未在临床试验中得到充分描述。我们在此报告 ICI 治疗后发生类风湿性关节炎 (RA) 和风湿性多肌痛 (PMR) 的病例。 方法 这是一项对接受 ICI 的患者进行的回顾性研究，这些患者出现关节炎或关节痛症状并诊断为 RA 或 PMR。 结果 在 10 名接受 ICI 治疗的患者中（均为抗 PD-1 或抗 PDL1 抗体），RA 或 PMR 在暴露后平均 1 个月（1 至 9 个月）出现。没有患者患有风湿病或自身免疫性疾病。 6 名患者出现 RA；所有六名患者的抗环瓜氨酸肽（抗 CCP）抗体呈阳性，四名患者的类风湿因子抗体呈阳性。在免疫治疗前接受测试的三分之二的患者中检测到了抗 CCP 抗体。三名患者需要缓解病情的抗风湿药物；另外三人接受皮质类固醇或非类固醇抗炎药。四名患者被诊断为 PMR，所有患者均对皮质类固醇有反应。尽管存在这些 IrAE，但除一名患者外，所有患者均继续接受免疫治疗，直至癌症进展。 结论 这是首次描述癌症 ICI 治疗后发生的 RA。 PMR 也可能在 ICI 之后发生，特别是在抗 PD-1 治疗后。所有病例均对皮质类固醇或免疫抑制治疗有反应。风湿病学家和肿瘤学家之间的合作至关重要，可以更好地认识和护理这些患者。
Objectives Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment.Methods This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR.Results In 10 patients who received ICI therapy (all anti-PD-1 or anti-PDL1 antibodies), RA or PMR developed at a median of 1 month (1 to 9) after exposure. No patient had pre-existing rheumatic or autoimmune disease. RA developed in six patients; all six were positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies and four for rheumatoid factor. Anti-CCP antibodies were detected in two out of three patients tested before immunotherapy. Disease-modifying antirheumatic drugs were needed for three patients; the three others received corticosteroids or non-steroid anti-inflammatory drugs. PMR was diagnosed in four patients, all responded to corticosteroids. Despite these IrAEs, immunotherapy was pursued for all but one patient until cancer progression.Conclusions This is the first description of RA occurring after ICI therapy for cancer. PMR can also occur after ICI, particularly after anti-PD-1 therapy. All cases responded to corticosteroids or with immunosuppressive therapy. Collaboration between rheumatologists and oncologists is crucial and could lead to better recognition and care of these patients.