Grümme Lea, Schulze-Koops Hendrik
Sektion Rheumatologie und Klinische Immunologie, Medizinische Klinik und Poliklinik IV, LMU Klinikum München, Pettenkoferstr. 8a, 80336, München, Deutschland.
Z Rheumatol. 2023 Apr;82(3):187-194. doi: 10.1007/s00393-022-01311-4. Epub 2023 Jan 6.
The spectrum of tumors for which checkpoint inhibitor (CI) treatment is used is constantly expanding. The European Medicines Agency has currently approved nine CIs: one anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) CI, one anti-lymphocyte activation gene 3 (LAG-3) CI, four anti-programmed cell death protein 1 (PD-1) CIs and three anti-programmed death ligand 1 (PD-L1) CIs. By blocking immune checkpoints the physiological downregulation of T cell activity against autologous tissue is prevented. This results in an immunologically unregulated activation of T cells directed against malignant cells. Healthy tissue also expresses antigens and thereby continuously activates autologous T cells. Thus, the blockade of immune checkpoints can lead to T cell activity against healthy tissue (immune-related adverse events, irAE). The irAEs can occur in any organ system and approximately 10% of all patients under CI treatment develop rheumatological irAEs, mostly arthralgia and myalgia. The classification criteria of rheumatological diseases do not need to be met to initiate treatment and the primary goal of treatment of irAEs is to enable continuation of CI treatment. Rheumatological irAEs should be recognized and treated quickly. In the treatment of musculoskeletal irAEs, three stages can be defined. In the first stage, nonsteroidal anti-inflammatory drugs or intra-articular as well as systemic glucocorticoids are used. In the second stage, conventional synthetic and in the third stage, biologic disease-modifying antirheumatic drugs are used. The most severe musculoskeletal irAE is myositis with cardiac and/or respiratory involvement and/or myasthenia gravis. In addition to high-dose glucocorticoids, intravenous immunoglobulins or plasma exchange are used in treatment.
使用检查点抑制剂(CI)治疗的肿瘤谱正在不断扩大。欧洲药品管理局目前已批准了9种CI:1种抗细胞毒性T淋巴细胞相关抗原4(CTLA-4)CI、1种抗淋巴细胞激活基因3(LAG-3)CI、4种抗程序性细胞死亡蛋白1(PD-1)CI和3种抗程序性死亡配体1(PD-L1)CI。通过阻断免疫检查点,可防止针对自体组织的T细胞活性出现生理性下调。这会导致针对恶性细胞的T细胞在免疫上不受调控地激活。健康组织也表达抗原,从而持续激活自体T细胞。因此,免疫检查点的阻断可导致T细胞针对健康组织产生活性(免疫相关不良事件,irAE)。irAE可发生于任何器官系统,接受CI治疗的所有患者中约10%会出现风湿性irAE,主要是关节痛和肌痛。启动治疗无需满足风湿性疾病的分类标准,irAE治疗的主要目标是能够继续进行CI治疗。风湿性irAE应迅速得到识别和治疗。在肌肉骨骼irAE的治疗中,可分为三个阶段。第一阶段使用非甾体抗炎药或关节内及全身糖皮质激素。第二阶段使用传统合成药物,第三阶段使用生物性抗风湿药物。最严重的肌肉骨骼irAE是伴有心脏和/或呼吸受累和/或重症肌无力的肌炎。除大剂量糖皮质激素外,治疗中还使用静脉注射免疫球蛋白或血浆置换。