Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases, and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the US Food and Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-associated ILD (SSc-ILD): nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, 2 generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy for the management of SSc-ILD is still to be determined. The objectives of this review are 2-fold: 1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and 2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical versus clinical ILD) and associated risk of progression (low versus high risk). The pharmacologic and nonpharmacologic options for first- and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD.

中文翻译：

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系统性硬化症相关间质性肺病：如何在临床实践中结合两种食品和药物管理局批准的疗法

系统性硬化症（SSc；硬皮病）在所有风湿性疾病中的个体死亡率最高，而间质性肺病（ILD）是 SSc 相关死亡的主要原因之一。两种药物现已获得美国食品和药物管理局 (FDA) 批准，用于减缓 SSc 相关间质性肺病 (SSc-ILD) 患者肺功能下降的速度：尼达尼布（一种酪氨酸激酶抑制剂）和托珠单抗（一种酪氨酸激酶抑制剂）第一种靶向 SSc 中白细胞介素 6 通路的生物制剂）。此外，霉酚酸酯和环磷酰胺这两种具有细胞毒性和免疫调节活性的仿制药在 II 期试验中显示出相当的疗效，但尚未获得 FDA 批准用于 SSc-ILD。鉴于疾病的异质性，管理 SSc-ILD 的最佳治疗策略仍有待确定。本综述的目标有两个：1) 回顾以 SSc-ILD 的诊断和治疗为重点的研究主体；2) 提出一种实用的诊断、分层、管理和治疗决策的方法。本综述根据疾病严重程度（亚临床与临床 ILD）和相关进展风险（低风险与高风险）对 SSc 患者进行了实用分类。根据最近批准用于 SSc-ILD 的托珠单抗，讨论了一线和二线治疗的药物和非药物选择，以及潜在的组合方法。和治疗决策在这种临床背景下。本综述根据疾病严重程度（亚临床与临床 ILD）和相关进展风险（低风险与高风险）对 SSc 患者进行了实用分类。根据最近批准用于 SSc-ILD 的托珠单抗，讨论了一线和二线治疗的药物和非药物选择，以及潜在的组合方法。和治疗决策在这种临床背景下。本综述根据疾病严重程度（亚临床与临床 ILD）和相关进展风险（低风险与高风险）对 SSc 患者进行了实用分类。根据托珠单抗最近批准用于 SSc-ILD 的情况，讨论了一线和二线治疗的药物和非药物选择，以及潜在的组合方法。