Rheumatology Unit, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Rheumatology Unit, Sheba Medical Center, Israel.
Autoimmun Rev. 2018 Mar;17(3):284-289. doi: 10.1016/j.autrev.2018.01.003. Epub 2018 Jan 16.
The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported.
To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel METHODS: The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts.
Rheumatic manifestations were encountered in 14 of 400 patients (3.5%) who had received immunotherapy between January 1st 2013 and April 30th, 2017. The most common rheumatic manifestation was inflammatory arthritis (85%) for which a third (4/11) had a clear cut predisposing factor such as a personal or family history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid therapy was beneficial in doses ≥20 mg/d. Methotrexate enabled steroid tapering without an excess of side effects or tumor progression in the short follow-up available. Overall, rheumatic manifestations tended to occur later in the course of immunotherapy as compared to other iAE.
Our findings underscore that rheumatic iAE are part of the side effect profile of ICIs and require heightened awareness as these therapies are becoming the standard of care for various malignancies. We show that these appear later in the course of iAEs and respond preferentially to high dose steroids. MTX appears effective as a steroid sparing agent.
自 2014 年首次批准以来，免疫检查点抑制剂（ICI）的使用一直在不断增长。这些单克隆抗体抑制 T 细胞激活，导致肿瘤反应明显，生存改善。然而，免疫疗法经常受到免疫不良反应（iAE）的阻碍，如垂体炎、结肠炎、肝炎、肺炎和皮疹。直到最近，风湿性副作用才被频繁报道。
描述在以色列一家大型三级癌症中心接受 ICI 治疗的患者中遇到的风湿表现。
筛选癌症中心的患者登记处，以寻找曾在 2013 年 1 月 1 日至 2017 年 4 月 30 日期间接受过伊匹单抗、派姆单抗和/或纳武单抗治疗的患者，并从临床图表中收集相关数据。
在 2013 年 1 月 1 日至 2017 年 4 月 30 日期间接受免疫治疗的 400 名患者中，有 14 名（3.5%）出现了风湿表现。最常见的风湿表现为炎症性关节炎（85%），其中三分之一（4/11）有明确的诱发因素，如个人或家族银屑病史、先前的虹膜炎或 ACPA 阳性。另外两名患者被诊断为肺结节病和活检证实的嗜酸性筋膜炎。非甾体抗炎药治疗大多无效，而剂量≥20mg/d 的类固醇治疗则有益。在可用的短期随访中，甲氨蝶呤使类固醇逐渐减少，且没有过度的副作用或肿瘤进展。总的来说，与其他 iAE 相比，风湿性 iAE 往往在免疫治疗过程中出现较晚。
我们的发现强调了风湿性 iAE 是 ICI 副作用谱的一部分，需要提高认识，因为这些疗法正成为各种恶性肿瘤的标准治疗方法。我们表明，这些在 iAE 过程中出现较晚，并且对高剂量类固醇有更好的反应。甲氨蝶呤作为一种类固醇节约剂似乎是有效的。
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