Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies
Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies
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DOI：
10.1007/s00262-017-2069-9
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发表时间：
2018-02-01
影响因子：
5.8
通讯作者：
Hassel, Jessica C.
中科院分区：
文献类型：
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作者：
Buder-Bakhaya, Kristina;Benesova, Karolina;Hassel, Jessica C.
背景 PD-1 抗体 (PD1ab) 越来越多地用于转移性黑色素瘤和其他恶性肿瘤。关节痛是 PD-1 抗体治疗的一种被低估的副作用，原因不明。我们的目的是表征 PD1ab 诱导的关节痛。 患者和方法 我们回顾性纳入 2013 年 1 月 1 日至 2016 年 9 月在国家肿瘤疾病中心（海德堡）接受派姆单抗或纳武单抗 +/- 伊匹单抗治疗的转移性皮肤恶性肿瘤患者。关节痛的特征是实验室诊断、影像学检查以及风湿科会诊（如有指征）。结果 195 名患者中有 26 名 (13.3%) 出现关节痛。症状出现的中位时间为 100 天（7-780 天）。最常见的是，关节痛以主要对称的方式涉及大关节（肩部、膝盖）。只有两名患者的类风湿因子和/或抗瓜氨酸蛋白抗体呈血清阳性。 10 名患者出现关节炎的临床表现，其中 7 名患者在 MRI 或 PET/CT 中显示滑膜炎。五名患者因骨关节炎而预先受损的关节出现炎症。 11 名患者的关节痛无法明确。大多数患者使用非甾体抗炎药 (NSAID) 得到满意的治疗，23.1% 的患者需要额外的低剂量皮质类固醇，只有 7.6% 的患者接受了进一步的免疫抑制治疗。关节痛患者表现出更好的治疗反应并改善 PFS 和 OS。结论 PD1ab 治疗期间关节痛很常见。临床表现在以大关节为主的滑膜炎、进行性骨关节炎和没有明显关节损伤的关节痛之间存在差异。绝大多数病例可以通过非甾体抗炎药和/或低剂量皮质类固醇得到满意的治疗。
Background PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia.Patients and methods We retrospectively included patients with metastatic cutaneous malignancies treated with pembrolizumab or nivolumab +/- ipilimumab at the National Center for Tumor Diseases (Heidelberg) between 01/2013 and 09/2016. Arthralgia was characterized by laboratory diagnostics, imaging, and if indicated, rheumatologic consultation.Results 26 of 195 patients (13.3%) developed arthralgia. The median onset of symptoms was 100 days (7-780 days). Most frequently, arthralgia involved large joints (shoulders, knees) in a predominantly symmetrical pattern. Only two patients were seropositive for rheumatoid factor and/or anti-citrullinated protein antibodies. Ten patients developed the clinical picture of arthritis, with seven of them showing synovitis in MRI or PET/CT. Five patients showed inflammation in joints pre-damaged by osteoarthritis. In 11 patients arthralgia could not be specified. The majority of patients was satisfactorily treated with non-steroidal anti-inflammatory drugs (NSAIDs), 23.1% required additional low-dose corticosteroids and only 7.6% of our patients received further immunosuppressive treatment. Patients with arthralgia showed a better treatment response and improved PFS and OS.Conclusion Arthralgia is frequent during PD1ab treatment. The clinical picture varies between synovitis of predominantly large joints, progressive osteoarthritis and arthralgia without evident joint damage. Vast majority of cases can be satisfactorily managed by NSAID and/or low-dose corticosteroids.