硬皮病肺研究期间的不良事件。

Adverse events during the Scleroderma Lung Study.

机构信息

David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90025, USA.

出版信息

Am J Med. 2011 May;124(5):459-67. doi: 10.1016/j.amjmed.2010.12.009.

DOI:10.1016/j.amjmed.2010.12.009

PMID:21531236

Abstract

BACKGROUND

The Scleroderma Lung Study (SLS) was a 1-year, randomized, controlled trial of oral cyclophosphamide for scleroderma-related pulmonary alveolitis. It concluded that oral cyclophosphamide slowed the decline in the forced vital capacity (% predicted) and had a beneficial effect on dyspnea, skin changes, and several quality of life measures of systemic sclerosis. We now report an in-depth assessment of the toxicity of cyclophosphamide during the year of therapy and the year after therapy was completed, during which time the investigators were still masked to the treatment assignment.

METHODS

One-year, double-blind, randomized controlled trial of oral cyclophosphamide versus placebo with 1-year masked follow-up. Adverse events (AEs) were tabulated, described, and compared using descriptive statistics (eg, mean and median) and t, Wilcoxon rank sum, chi-squared, or Fisher's exact tests as appropriate.

RESULTS

During year 1, treatment-related overall AEs occurred more frequently in cyclophosphamide (CYC)-treated patients (overall AEs for CYC=154 events vs placebo=60 events; P=0.002), and especially for mild to moderate leukopenia (CYC=19 subjects vs placebo=0 subjects; P < .0001). For cancer, we followed patients beyond 2 years. There were no differences in the occurrence of cancer (CYC=4 subjects vs placebo=2 subjects), serious related AEs (CYC=8 events vs placebo=13 events), or deaths (CYC=6 subjects vs placebo=6 subjects).

CONCLUSION

Over 2 years, cyclophosphamide was associated with more AEs than placebo, including overall AEs and relative leukopenia. There were no differences in other AEs, including serious AEs, cancers, or deaths.

摘要

背景

硬皮病肺研究（SLS）是一项为期 1 年的随机对照试验，旨在研究口服环磷酰胺治疗硬皮病相关肺泡炎的疗效。该试验的结论是，口服环磷酰胺可减缓用力肺活量（%预计值）的下降速度，并对呼吸困难、皮肤变化和系统性硬化症的几个生活质量指标有有益影响。我们现在报告对治疗期间和治疗结束后 1 年环磷酰胺毒性的深入评估，在此期间，研究人员仍对治疗分配情况进行了盲法评估。

方法

一项为期 1 年的口服环磷酰胺与安慰剂的双盲随机对照试验，随后进行了 1 年的随访。使用描述性统计（例如，均值和中位数）和 t 检验、Wilcoxon 秩和检验、卡方检验或 Fisher 确切检验等适当的方法，对不良事件（AE）进行列表、描述和比较。

结果

在第 1 年，环磷酰胺（CYC）治疗组患者发生的与治疗相关的总体 AE 更为频繁（CYC 组的总体 AE 为 154 例，安慰剂组为 60 例；P=0.002），尤其是轻度至中度白细胞减少症（CYC 组 19 例，安慰剂组 0 例；P<.0001）。对于癌症，我们对患者进行了超过 2 年的随访。在癌症（CYC 组 4 例，安慰剂组 2 例）、严重相关 AE（CYC 组 8 例，安慰剂组 13 例）或死亡（CYC 组 6 例，安慰剂组 6 例）的发生方面，两组无差异。