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首页> 外文期刊>Rheumatology >A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications: safety and efficacy of combination therapy with imatinib and cyclophosphamide.
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A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications: safety and efficacy of combination therapy with imatinib and cyclophosphamide.

机译：一种新的治疗硬皮病相关肺部并发症的方法：伊马替尼和环磷酰胺联合治疗的安全性和有效性。

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OBJECTIVE: Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. METHODS: Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. RESULTS: Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. CONCLUSION: The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.
机译：目的：与硬皮病相关的间质性肺疾病（SSc-ILD）由于发病机理不清楚，因此治疗选择有限。最近，已经假定PDGF受体（PDGFR）的扩增会引起纤维化。我们假设免疫抑制剂的组合例如环磷酰胺（CYC）和伊马替尼（PDGFR抑制剂），可能用于治疗与SSc相关的ILD。我们的目的是评估这种组合疗法在硬皮病相关的肺部疾病中的安全性和有效性。方法：对5例晚期SSc-ILD患者进行了全面的心肺评估，然后口服伊马替尼（200 mg /天）和静脉CYC（每3周500 mg）。通过密切监测全血细胞计数，肝和心脏功能来评估安全性。通过测量6个月和12个月的肺功能来评估疗效。结果：在研究的五名患者中，四名患有严重的肺病，另一名患有轻度的限制性肺病。所有患者均耐受联合治疗，无骨髓抑制，肝功能恶化或心脏状态恶化。只有一名患者出现轻度液体超负荷，需要利尿剂。两名患者完成了1年的治疗。仅患有轻度限制性肺部疾病的患者显示肺功能有所改善。结论：静脉内CYC联合口服伊马替尼耐受性好，无重大副作用。仅轻度限制性疾病患者可见临床改善。据我们所知，这是第一个研究伊马替尼联合CYC在硬皮病相关肺疾病中的安全性，耐受性和功效的研究。需要进行大规模的前瞻性试验，以进一步确定该方案的最佳时机，剂量和持续时间。

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