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托珠单抗成功治疗免疫检查点抑制剂相关关节炎:病例系列。

Successful treatment of arthritis induced by checkpoint inhibitors with tocilizumab: a case series.

机构信息

Department of General Internal Medicine, Section of Rheumatology and Clinical Immunology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

出版信息

Ann Rheum Dis. 2017 Dec;76(12):2061-2064. doi: 10.1136/annrheumdis-2017-211560. Epub 2017 Aug 22.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with numerous cancers. However, these therapies are associated with immune-related adverse events (irAEs), which are inflammatory side effects potentially affecting any organ. Cases of ICI-induced inflammatory arthritis have also been reported. In general, mild irAEs are treated with corticosteroids, while tumour necrosis factor-α (TNFα) inhibitors are reserved for refractory cases. However, prolonged use of TNFα inhibitor (TNFαi) can induce widespread, significant immunosuppression, which can negatively impact the antitumour efficacy of ICI therapy. Therefore, in clinical scenarios where patients develop severe immunotherapy-induced irAEs, an unmet need exists for alternative therapeutic strategies that are effective and without immune dampening effects.

CASE REPORTS

The anti-interleukin (IL)-6 receptor antibody, tocilizumab, is a biological agent Food and Drug Administration approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Here, we report on three patients who developed severe polyarthritis while receiving ICI therapy and were treated with tocilizumab. All three patients demonstrated significant clinical improvement; one patient maintained a durable antitumour response derived from checkpoint inhibition.

CONCLUSIONS

These three cases suggest that anti-IL-6 receptor antibody may be an effective alternative to corticosteroids or TNFαi for the treatment of arthritis irAEs.

摘要

背景

免疫检查点抑制剂(ICI)显著改善了许多癌症患者的预后。然而,这些疗法与免疫相关的不良反应(irAE)有关,这些不良反应可能影响任何器官的炎症副作用。ICI 诱导的炎性关节炎的病例也有报道。一般来说,轻度 irAE 用皮质类固醇治疗,而肿瘤坏死因子-α(TNFα)抑制剂则保留用于难治性病例。然而,TNFα 抑制剂(TNFαi)的长期使用会引起广泛的、显著的免疫抑制,从而对 ICI 治疗的抗肿瘤疗效产生负面影响。因此,在患者发生严重免疫治疗诱导的 irAE 的临床情况下,需要有效的替代治疗策略,而这些策略不应具有免疫抑制作用。

病例报告

抗白细胞介素(IL)-6 受体抗体托珠单抗是一种已获美国食品和药物管理局批准用于治疗类风湿关节炎和幼年特发性关节炎的生物制剂。在这里,我们报告了三例在接受 ICI 治疗时发生严重多关节炎的患者,并接受了托珠单抗治疗。所有三名患者均表现出显著的临床改善;一名患者保持了来自检查点抑制的持久抗肿瘤反应。

结论

这三个案例表明,抗 IL-6 受体抗体可能是皮质类固醇或 TNFαi 治疗关节炎 irAE 的有效替代药物。

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