Tashkin Donald P, Elashoff Robert, Clements Philip J, Goldin Jonathan, Roth Michael D, Furst Daniel E, Arriola Edgar, Silver Richard, Strange Charlie, Bolster Marcy, Seibold James R, Riley David J, Hsu Vivien M, Varga John, Schraufnagel Dean E, Theodore Arthur, Simms Robert, Wise Robert, Wigley Fredrick, White Barbara, Steen Virginia, Read Charles, Mayes Maureen, Parsley Ed, Mubarak Kamal, Connolly M Kari, Golden Jeffrey, Olman Mitchell, Fessler Barri, Rothfield Naomi, Metersky Mark
University of California at Los Angeles, Los Angeles, USA.
N Engl J Med. 2006 Jun 22;354(25):2655-66. doi: 10.1056/NEJMoa055120.
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.
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 (< or =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.
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.
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.
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有活动性肺泡炎和硬皮病相关间质性肺病证据的患者肺功能和健康相关症状的影响。
在美国的13个临床中心，我们纳入了158例患有硬皮病、限制性肺生理学、呼吸困难且经支气管肺泡灌洗、胸部高分辨率计算机断层扫描或两者检查有炎症性间质性肺病证据的患者。患者接受口服环磷酰胺（≤2毫克/千克体重/天）或匹配的安慰剂治疗一年，并随访额外一年。在第一年中每三个月评估一次肺功能，主要终点是在调整基线用力肺活量（FVC）后12个月时的用力肺活量（以预测值的百分比表示）。
158例患者中，145例完成了至少六个月的治疗并纳入分析。环磷酰胺组和安慰剂组之间调整后的12个月FVC预测百分比的平均绝对差异为2.53%（95%置信区间，0.28%至4.79%），支持环磷酰胺组（P<0.03）。在生理和症状结果方面也存在与治疗相关的差异，并且FVC的差异在24个月时仍然存在。环磷酰胺组不良事件的发生率更高，但两组之间严重不良事件的数量差异不显著。
对有症状的硬皮病相关间质性肺病患者口服环磷酰胺一年对肺功能、呼吸困难、皮肤增厚和健康相关生活质量有显著但适度的有益影响。在研究的24个月期间，对肺功能的影响持续存在。
