A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma
A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma
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DOI：
10.1002/art.22204
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发表时间：
2006-12-01
影响因子：
--
通讯作者：
du Bois, Roland M.
中科院分区：
文献类型：
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作者：
Hoyles, Rachel K.;Ellis, Ross W.;du Bois, Roland M.
目标。系统性硬化症（SSc）肺纤维化的随机对照试验（rct）的缺乏阻碍了循证治疗方法的发展。本随机对照试验旨在探讨静脉注射（IV）环磷酰胺（CYC）和硫唑嘌呤（AZA）治疗SSc肺纤维化的效果。方法。45名患者随机接受低剂量强的松龙和6次CYC输注（每月），随后口服AZA或安慰剂。主要结局指标为预测用力肺活量（FVC）百分比的变化和单呼吸一氧化碳扩散能力（DLco）的变化。次要结果测量包括高分辨率计算机断层扫描和呼吸困难评分的外观变化。进行意向治疗统计分析。结果。在基线时，与结果相关的因素，包括肺纤维化的严重程度和自身抗体状态，没有显著的组间差异。62%的患者完成了第一年的治疗。停药包括9例患者（6例来自安慰剂组），肺功能明显下降，2例有治疗副作用（均来自积极治疗组），6例有非试验相关的合并症。未见出血性膀胱炎或骨髓抑制。对基线FVC和治疗中心校正后的相对治疗效果（积极治疗vs安慰剂）的估计显示，FVC的有利结果为4.19%；组间差异有统计学意义（P = 0.08）。未发现DLco或次要结局指标的改善。结论。该试验未显示积极治疗组与安慰剂组相比在主要或次要终点有显著改善。两组间FVC差异有统计学意义。这表明，低剂量强的松龙和IV CYC联合AZA治疗SSc肺纤维化可以稳定一部分患者的肺功能。治疗耐受性良好，严重不良事件未增加。
Objective. The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence-based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc. Methods. Forty-five patients were randomized to receive low-dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single-breath diffusing capacity for carbon monoxide (DLco). Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores. An intent-to-treat statistical analysis was performed. Results. At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty-two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non-trial-related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between-group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLco or secondary outcome measures were identified. Conclusion. This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.