Ueda Takahiro, Sakagami Takuro, Kikuchi Toshiaki, Takada Toshinori
Clinical and Translational Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Respir Investig. 2018 Jan;56(1):14-20. doi: 10.1016/j.resinv.2017.11.004. Epub 2017 Dec 6.
Systemic sclerosis (SSc) is an intractable disease that causes fibrosis in all organs. Approximately 40% of patients with SSc have some degree of interstitial lung disease (ILD). One third of patients with SSc and ILD, approximately 15% of all patients, have pulmonary lesions, which slowly progress to respiratory failure resistant to corticosteroid and other treatments. A randomized controlled trial conducted in the United States indicated that one year of treatment with oral cyclophosphamide in patients with SSc-ILD had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and health-related quality of life. However, all the effects, except for a sustained impact on dyspnea, disappeared approximately one year after stopping oral administration of cyclophosphamide. A randomized controlled trial using cyclophosphamide and mycophenolate mofetil (MMF) was then held in the United States for 142 patients with SSc-ILD. Treatment of SSc-ILD with MMF for two years or cyclophosphamide for one year both resulted in significant improvements in lung function over the 2-year course of the study. Leukopenia and thrombocytopenia occurred less often in patients administered MMF than in those administered cyclophosphamide. MMF is currently not approved for the treatment of SSc-ILD in Japan. Both MMF and cyclophosphamide were effective against ILD associated with SSc and, in particular, MMF was useful in terms of tolerability. When MMF is approved, it should be positioned as one of the first treatment options for SSc-ILD, which will further enhance the treatment of this disease in Japan.
系统性硬化症（SSc）是一种难治性疾病，可导致所有器官发生纤维化。约40%的SSc患者有一定程度的间质性肺疾病（ILD）。三分之一的SSc合并ILD患者，约占所有患者的15%，有肺部病变，这些病变会缓慢进展为对皮质类固醇和其他治疗耐药的呼吸衰竭。在美国进行的一项随机对照试验表明，SSc-ILD患者口服环磷酰胺治疗一年对肺功能、呼吸困难、皮肤增厚及健康相关生活质量有显著但适度的有益影响。然而，除了对呼吸困难有持续影响外，停止口服环磷酰胺约一年后，所有这些影响均消失。随后在美国对142例SSc-ILD患者进行了一项使用环磷酰胺和霉酚酸酯（MMF）的随机对照试验。在为期2年的研究过程中，用MMF治疗SSc-ILD两年或用环磷酰胺治疗一年均使肺功能有显著改善。接受MMF治疗的患者白细胞减少和血小板减少的发生率低于接受环磷酰胺治疗的患者。目前MMF在日本未被批准用于治疗SSc-ILD。MMF和环磷酰胺对SSc相关的ILD均有效，特别是MMF在耐受性方面很有用。当MMF获得批准时，应将其定位为SSc-ILD的首选治疗方案之一，这将进一步加强日本对该疾病的治疗。
