Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
J Rheumatol. 2011 Oct;38(10):2186-92. doi: 10.3899/jrheum.110499. Epub 2011 Sep 1.
To evaluate the clinical benefits of the endothelin receptor antagonist bosentan on interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) who are ineligible for cyclophosphamide (CYC) therapy.
In this prospective open-label study, 9 patients with SSc and ILD received bosentan for 24 months. The main reasons for avoiding CYC included severely impaired lung function, long disease duration, and relapse after CYC treatment. Pulmonary function tests and Doppler echocardiograms were evaluated every 6 months, and high-resolution computed tomography (HRCT) was performed every 12 months. For an extended survival analysis, 17 historical controls who met the inclusion criteria at referral and had not used any immunosuppressive or antifibrotic agents thereafter were selected from the SSc database.
Two patients did not finish the study; one developed vasculitis requiring high-dose corticosteroids and another died of bacterial pneumonia. The remaining 7 patients tolerated bosentan and completed the study period. There were trends toward mildly reduced forced vital capacity, total lung capacity, and diffusing capacity for carbon monoxide over time. Two patients developed pulmonary hypertension during the 24-month period. HRCT scores for ground-glass opacity, pulmonary fibrosis, and honeycomb cysts gradually increased. In the extended study, there was no difference in cumulative survival rate between the bosentan-treated and historical control groups.
The gradual worsening of pulmonary function and HRCT findings in patients treated with bosentan was consistent with the natural course of SSc-associated ILD. This study does not support the use of bosentan for SSc-associated ILD even when CYC treatment is inadvisable.
评估内皮素受体拮抗剂波生坦治疗不能接受环磷酰胺（CYC）治疗的系统性硬化症（SSc）患者间质性肺病（ILD）的临床获益。
在这项前瞻性开放标签研究中，9 名 SSc 合并 ILD 患者接受波生坦治疗 24 个月。避免使用 CYC 的主要原因包括严重受损的肺功能、较长的疾病病程和 CYC 治疗后复发。每 6 个月评估肺功能测试和多普勒超声心动图，每 12 个月进行高分辨率计算机断层扫描（HRCT）。为了进行扩展生存分析，从 SSc 数据库中选择了 17 名符合纳入标准但在转诊后未使用任何免疫抑制剂或抗纤维化药物的历史对照。
2 名患者未完成研究；1 名患者发生血管炎，需要大剂量皮质类固醇治疗，另 1 名患者死于细菌性肺炎。其余 7 名患者耐受了波生坦并完成了研究期。用力肺活量、总肺活量和一氧化碳弥散量随时间呈轻度降低趋势。2 名患者在 24 个月期间发生肺动脉高压。磨玻璃影、肺纤维化和蜂窝状囊肿的 HRCT 评分逐渐增加。在扩展研究中，波生坦治疗组和历史对照组的累积生存率无差异。
波生坦治疗患者的肺功能和 HRCT 发现逐渐恶化，与 SSc 相关的 ILD 自然病程一致。即使 CYC 治疗不合适，本研究也不支持使用波生坦治疗 SSc 相关的 ILD。
