Efficacy of cyclophosphamide for skin fibrosis in systemic sclerosis: a systematic review and single-arm meta-analysis.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-04-08 DOI:10.1007/s00228-025-03837-3

Xin Tian, PengJiao An, RongJi Liu, Wei Zuo, Xin Liu, ZaiWei Song, Yang Hu, RongSheng Zhao, Bo Zhang

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引用次数: 0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: PROSPERO registration number: CRD42024502283. Registered on 25 January 2024.

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环磷酰胺治疗系统性硬化症皮肤纤维化的疗效：一项系统评价和单臂荟萃分析。

目的：系统性硬化症（SSc）是一种慢性结缔组织疾病，其特征是皮肤增厚并累及血管和内脏。环磷酰胺治疗ssc相关皮肤纤维化的疗效仍有争议。本研究的目的是评估环磷酰胺治疗SSc皮肤纤维化的有效性。方法：系统检索PubMed、Embase、Cochrane图书馆和ClinicalTrials.gov数据库，检索截至2025年1月15日所有已发表的关于环磷酰胺治疗SSc的临床试验。关注的结果是皮肤纤维化的程度，用改良罗德曼皮肤评分（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。meta分析采用Stata/SE软件。结果：共有20篇文章869例患者符合纳入标准。环磷酰胺在6、12、18、24和36个月分别使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）。通过汇总所有研究的mRSS在随访终点获得的估计效应量减少了4.71 （95% CI 2.72-6.70）。在弥漫性皮肤SSc （dcSSc）亚型中，总mRSS在6、12、18和24个月分别下降了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，随访结束时dcSSc的mRSS总体降低为7.30 （95% CI 5.61-8.99）。在这些研究中观察到显著的异质性，亚组分析显示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。结论：环磷酰胺可有效降低SSc，尤其是dcSSc的mRSS评分。虽然皮肤厚度的改善在24个月后会减弱，但对于皮肤纤维化恶化的患者来说，它仍然是一个可行的选择。试验注册：PROSPERO注册号：CRD42024502283。于2024年1月25日注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.