Cyclophosphamide versus placebo in scleroderma lung disease
Cyclophosphamide versus placebo in scleroderma lung disease
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DOI：
10.1056/nejmoa055120
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发表时间：
2006-06-22
影响因子：
158.5
通讯作者：
Metersky, Mark
中科院分区：
文献类型：
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作者：
Tashkin, Donald P.;Elashoff, Robert;Metersky, Mark
背景：我们进行了一项双盲、随机、安慰剂对照试验，以确定口服环磷酰胺对活动性肺泡炎和硬皮病相关性间质性肺疾病患者的肺功能和健康相关症状的影响。方法：在美国13个临床中心，我们招募了158名硬皮病、限制性肺生理、呼吸困难和炎性间质性肺病患者，他们接受了支气管肺泡灌洗液检查、胸部高分辨率计算机断层扫描或两者兼有的检查。患者接受口服环磷酰胺(每天每公斤体重小于或等于2毫克)或匹配的安慰剂治疗一年，并再随访一年。第一年每3个月评估一次肺功能，主要终点是根据基线FVC调整后12个月的用力肺活量(FVC，以预测值的百分比表示)。结果：在158例患者中，145例完成了至少6个月的治疗，并进入分析。环磷酰胺组和安慰剂组调整后12个月FVC预测百分比的平均绝对差值为2.53%(95%可信区间为0.28%至4.79%)，有利于环磷酰胺(P<；0.03)。在生理和症状结果上也存在与治疗相关的差异，FVC的差异维持在24个月。环磷酰胺组不良事件发生率较高，但两组严重不良事件发生次数差异无统计学意义。结论：环磷酰胺口服1年对硬皮病相关性间质性肺疾病患者的肺功能、呼吸困难、皮肤增厚及健康相关生活质量均有明显但不明显的改善作用。在24个月的研究过程中，对肺功能的影响一直保持不变。
Background: We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease.Methods: At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received oral cyclophosphamide (lessthan/equal 2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC.Results: Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P < 0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant.Conclusions: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.