Division of Medical Oncology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Semin Arthritis Rheum. 2019 Jun;48(6):1127-1132. doi: 10.1016/j.semarthrit.2018.10.012. Epub 2018 Oct 16.
The use of immune checkpoint inhibition (ICI) has revolutionized cancer treatment. However, these medications are associated with significant and potentially debilitating immune-related adverse events (irAEs). While certain toxicities have been well studied, rheumatic complications have been less widely recognized and characterized.
We report our experience of patients who were evaluated by rheumatology after the development of a suspected rheumatic irAE following ICI treatment. Cases of rheumatic irAEs were included if active rheumatic signs or symptoms developed during or after ICI treatment and were confirmed by a treating rheumatologist.
Twenty-nine patients were evaluated by rheumatology for suspected rheumatic irAEs. Eighteen patients had confirmed toxicity including inflammatory arthritis (n = 12) and PMR (n = 6). Twelve patients had de novo toxicity and six had a flare of a pre-existing rheumatic condition. The onset of de novo toxicity occurred late into treatment (median 38 weeks), while patients with pre-existing rheumatic disease flared soon after initiation of ICI treatment (median 4.6 weeks). Management often required systemic or intra-articular steroids, with initiation of disease modifying anti-rheumatic drug (DMARD) therapy in those unable to wean off steroids.
De novo rheumatic irAEs are generally delayed in onset after ICI initiation, while flares of pre-existing rheumatic conditions occur shortly after ICI initiation. Effective management often requires systemic corticosteroids as well as DMARDs in a subset of patients. Future prospective studies are needed to accurately describe the incidence and spectrum of rheumatic irAEs and to identify the most effective management strategies.
免疫检查点抑制(ICI)的应用彻底改变了癌症治疗。然而,这些药物与严重且可能使人衰弱的免疫相关不良事件(irAEs)有关。虽然某些毒性已经得到了广泛研究,但风湿并发症的认识和特征还不够广泛。
我们报告了在接受 ICI 治疗后出现疑似风湿性 irAE 的患者,经风湿病学评估的经验。如果在 ICI 治疗期间或之后出现活动性风湿性体征或症状,并经治疗风湿病医生确认,则将风湿性 irAE 病例纳入研究。
有 29 名患者因疑似风湿性 irAE 接受了风湿病学评估。18 名患者被确诊为毒性反应,包括炎症性关节炎(n=12)和 PMR(n=6)。12 名患者为新发毒性反应,6 名患者为原有风湿性疾病的发作。新发毒性反应的发生时间较晚(中位数 38 周),而原有风湿性疾病的患者在开始 ICI 治疗后很快发作(中位数 4.6 周)。治疗通常需要全身或关节内类固醇,对于无法停用类固醇的患者,需要开始使用疾病修饰抗风湿药物(DMARD)治疗。
ICI 起始后新发风湿性 irAE 的发病时间通常较晚,而原有风湿性疾病的发作发生在 ICI 起始后不久。有效的治疗通常需要全身皮质类固醇以及一部分患者的 DMARDs。未来需要前瞻性研究来准确描述风湿性 irAE 的发生率和谱,并确定最有效的管理策略。