Tian Xin, An PengJiao, Liu RongJi, Zuo Wei, Liu Xin, Song ZaiWei, Hu Yang, Zhao RongSheng, Zhang Bo
Department of Pharmacy, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
Department of Pharmacy, Peking University Third Hospital, No.49 Huayuan North Road, Haidian District, Beijing, 100191, China.
Eur J Clin Pharmacol. 2025 Jun;81(6):863-874. doi: 10.1007/s00228-025-03837-3. Epub 2025 Apr 8.
Systemic sclerosis (SSc) is a chronic connective tissue disorder characterized by skin thickening with vascular and visceral involvements. The efficacy of cyclophosphamide for SSc-related skin fibrosis remains controversial. The aim of this study was to evaluate the effectiveness of cyclophosphamide for skin fibrosis in SSc.
PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov databases were systematically searched for all published clinical trials on the treatment of SSc with cyclophosphamide until January 15, 2025.The outcome of interest was the extent of skin fibrosis, measured by the modified Rodnan skin score (mRSS). Two authors independently screened studies, extracted data, and evaluated the risk of bias. Meta-analysis was conducted with Stata/SE software.
A total of 20 articles involving 869 patients met the inclusion criteria. Cyclophosphamide reduced mRSS score by 2.30 (95% CI 0.72-3.88), 4.53 (95% CI 2.91-6.14), 6.72 (95% CI 2.74-10.70), 5.70 (95% CI 4.04-7.36), and 4.60 (95% CI 3.18-6.02) at 6-, 12-, 18-, 24- and 36-month, respectively. The estimated effect size, obtained by pooling mRSS from all studies at the follow-up endpoint, decreased by 4.71 (95% CI 2.72-6.70). In diffuse cutaneous SSc (dcSSc) subtype, the pooled mRSS decreased by 3.02 (95% CI 1.46-4.58), 6.45 (95% CI 5.02-7.87), 8.03 (95% CI 5.26-10.80), and 6.34 (95% CI 6.00-6.68) at 6-, 12-, 18-, and 24-month, respectively. And the overall reduction in mRSS at the end of follow-up in dcSSc was 7.30 (95% CI 5.61-8.99) across 11 studies. Significant heterogeneity was observed among these studies, and subgroup analysis revealed that study size and disease subtype partially explained the heterogeneity. Sensitivity analysis indicated good study stability.
Cyclophosphamide effectively reduced mRSS scores in SSc, particularly in dcSSc. While skin thickness improvement diminishes after 24 months, it remains a viable option for patients with worsening skin fibrosis.
PROSPERO registration number: CRD42024502283. Registered on 25 January 2024.
系统性硬化症（SSc）是一种慢性结缔组织疾病，其特征为皮肤增厚并伴有血管和内脏受累。环磷酰胺治疗SSc相关皮肤纤维化的疗效仍存在争议。本研究旨在评估环磷酰胺对SSc皮肤纤维化的有效性。
系统检索PubMed、Embase、Cochrane图书馆和ClinicalTrials.gov数据库，以获取截至2025年1月15日所有已发表的关于用环磷酰胺治疗SSc的临床试验。感兴趣的结局是皮肤纤维化程度，通过改良Rodnan皮肤评分（mRSS）来衡量。两位作者独立筛选研究、提取数据并评估偏倚风险。使用Stata/SE软件进行荟萃分析。
共有20篇涉及869例患者的文章符合纳入标准。环磷酰胺在6个月、12个月、18个月、24个月和36个月时分别使mRSS评分降低2.30（95%CI 0.72 - 3.88）、4.53（95%CI 2.91 - 6.14）、6.72（95%CI 2.74 - 10.70）、5.70（95%CI 4.04 - 7.36）和4.60（95%CI 3.18 - 6.02）。通过在随访终点汇总所有研究的mRSS获得的估计效应量降低了4.71（95%CI 2.72 - 6.70）。在弥漫性皮肤型SSc（dcSSc）亚型中，在6个月、12个月、18个月和24个月时，汇总的mRSS分别降低3.02（95%CI 1.46 - 4.58）、6.45（95%CI 5.02 - 7.87）、8.03（95%CI 5.26 - 10.80）和6.34（95%CI 6.00 - 6.68）。在11项研究中，dcSSc随访结束时mRSS的总体降低为7.30（95%CI 5.61 - 8.99）。这些研究之间观察到显著的异质性，亚组分析表明研究规模和疾病亚型部分解释了异质性。敏感性分析表明研究稳定性良好。
环磷酰胺可有效降低SSc患者的mRSS评分，尤其是在dcSSc患者中。虽然24个月后皮肤厚度改善有所减少，但对于皮肤纤维化恶化的患者而言，它仍是一个可行的选择。
PROSPERO注册号：CRD42024502283。于2024年1月25日注册。
