Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab.
Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab.
复制标题
DOI：
10.1136/annrheumdis-2016-209595
复制
发表时间：
2017-01
影响因子：
27.4
通讯作者：
Bingham CO 3rd
中科院分区：
文献类型：
--
作者：
Cappelli LC;Gutierrez AK;Baer AN;Albayda J;Manno RL;Haque U;Lipson EJ;Bleich KB;Shah AA;Naidoo J;Brahmer JR;Le D;Bingham CO 3rd
针对细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)通路的免疫检查点抑制物(ICIS)已证明可改善多种晚期癌症的生存率，但也会导致免疫相关不良事件(IRAE)。具有与风湿性疾病相似的临床特征的IRAE尚未得到很好的描述。我们报告了继发于ICIS的炎性关节炎和干燥综合征的患者。我们报告了2012至2016年间在约翰霍普金斯风湿病诊所接受评估的患者，在使用ipilimumab(抗CTLA-4)和/或nivolumab(抗PD-1)治疗实体肿瘤的背景下，发现有新的风湿病症状。我们确定了13名接受ICIS并发展为风湿性IRAE的患者。平均年龄58.7岁。癌症类型包括黑色素瘤、非小细胞肺癌、小细胞肺癌和肾癌。ICI方案包括尼伏单抗或ipilimumab作为单一治疗方案(n=5)，或nivolumab和ipilimumab联合治疗(n=8)。13例患者中有9例发展为炎性关节炎，4例经影像检查(3例超声、1例MRI)确诊为滑膜炎，4例为炎性滑液。4例患者出现干燥综合征，并伴有严重的唾液功能减退。其他IRAE包括：肺炎、结肠炎、间质性肾炎和甲状腺炎。13例患者中有5例抗核抗体阳性。13例患者均接受了糖皮质激素治疗，但疗效各不相同。两名患者接受甲氨蝶呤和抗肿瘤坏死因子治疗炎性关节炎。随着ICIS越来越多地用于一系列恶性肿瘤，可能会出现新的风湿性IRAE病例。需要进一步的研究来了解机制，确定风险因素，并开发风湿性IRAE的管理算法。
Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours. We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis. As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.