Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Patras, Greece.
Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41 110, Larissa, Greece.
Rheumatol Int. 2021 Jan;41(1):33-42. doi: 10.1007/s00296-020-04665-7. Epub 2020 Aug 2.
Immune checkpoint inhibitors (ICI) associate with a wide range of immune-related adverse events (Ir-AE), including musculoskeletal manifestations. We aimed at identifying all studies reporting musculoskeletal Ir-AE. An electronic (Medline, Scopus and Web of Science) search was performed using two sets of key words. The first set consisted of: arthritis, musculoskeletal, polymyalgia rheumatica and myositis. The second set consisted of: anti-PD-1, anti-PD-L1, anti-CTLA-4, ipilimumab, tremelimumab, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab. We identified 3 prospective studies, 17 retrospective studies and 4 case series reporting 363 patients in total. Combined data from all three prospective studies provide a prevalence rate of 6.13%. Most patients were males (59.68%) and the vast majority (73%) were on programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors. Most studies report a median time of ≤ 12 weeks from first ICI administration to symptom onset. The main clinical phenotypes reported were: (a) inflammatory arthritis (57.57%), (b) myositis (14.04%) and (c) polymyalgia rheumatica (PMR) (12.12%). A total of 256 patients required steroids (70.52%) and 67 patients (18.45%) were treated with DMARDs. Positive auto-antibodies and family history of any autoimmune disease were present in 18.48% and 19.04% of cases, respectively. Only a few patients (19%) had to discontinue treatment due to musculoskeletal Ir-AE. Two prospective studies show that significantly more patients with musculoskeletal Ir-AE exhibit a favorable oncologic response compared to patients not exhibiting such manifestations whereas retrospective studies show that 77.22% of patients with musculoskeletal Ir-AE have a good tumor response. One out of 15 patients treated with ICI will develop musculoskeletal Ir-AE; in most cases the severity of these manifestations is mild/moderate and usually ICI may be continued. Rheumatologists should familiarize with this new clinical entity and develop relevant therapeutic algorithms.
免疫检查点抑制剂（ICI）与广泛的免疫相关不良事件（Ir-AE）相关，包括肌肉骨骼表现。我们旨在确定所有报告肌肉骨骼 Ir-AE 的研究。使用两组关键词进行了电子（Medline、Scopus 和 Web of Science）搜索。第一组包括：关节炎、肌肉骨骼、风湿性多肌痛和肌炎。第二组包括：抗 PD-1、抗 PD-L1、抗 CTLA-4、伊匹单抗、替西木单抗、帕博利珠单抗、纳武单抗、阿特珠单抗、avelumab 和度伐鲁单抗。我们总共确定了 3 项前瞻性研究、17 项回顾性研究和 4 项病例系列研究，共报告了 363 例患者。所有三项前瞻性研究的数据合并后，患病率为 6.13%。大多数患者为男性（59.68%），绝大多数（73%）接受程序性死亡-1（PD-1）/程序性死亡配体-1（PD-L1）抑制剂治疗。大多数研究报告从首次接受 ICI 治疗到症状出现的中位时间为≤12 周。报告的主要临床表型包括：（a）炎症性关节炎（57.57%）、（b）肌炎（14.04%）和（c）风湿性多肌痛（PMR）（12.12%）。总共 256 例患者需要使用类固醇（70.52%），67 例患者（18.45%）接受 DMARD 治疗。阳性自身抗体和任何自身免疫性疾病家族史分别存在于 18.48%和 19.04%的病例中。只有少数患者（19%）因肌肉骨骼 Ir-AE 而不得不停止治疗。两项前瞻性研究表明，与未出现此类表现的患者相比，肌肉骨骼 Ir-AE 患者表现出更好的肿瘤反应的比例显著更高，而回顾性研究表明，77.22%的肌肉骨骼 Ir-AE 患者具有良好的肿瘤反应。在接受 ICI 治疗的 15 例患者中，有 1 例出现肌肉骨骼 Ir-AE；在大多数情况下，这些表现的严重程度为轻度/中度，通常可以继续使用 ICI。风湿病学家应该熟悉这一新的临床实体，并制定相关的治疗方案。
