Efficacy and safety of aldafermin for the treatment of metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2025-03-25 DOI:10.1016/j.clinre.2025.102579

Samira Mohamad Khalil , Matheus Henrique Gonçalves de Souza , Fabiana Dolovitsch de Oliveira , Emmily Daiane Buarque de Santana Sato , Gilmara Coelho Meine

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引用次数: 0

Abstract

Background

We aimed to assess the efficacy and safety of Aldafermin in treating patients with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH).

Methods

We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing Aldafermin to placebo for treating patients with MASH up to December 8, 2024. The risk ratios (RR) with 95 % confidence intervals (CI) were pooled for binary outcomes using a random-effects model. Additionally, we conducted subgroup analysis by fibrosis stage and Aldafermin dosage, and meta-regression analysis assuming the dosage of Aldafermin as a covariate.

Results

We included 4 RCTs, encompassing 491 patients. Compared to placebo, Aldafermin had a higher probability of MASH resolution without worsening of fibrosis (RR 3.04; 95 %CI 1.12–8.28), composite of fibrosis improvement and MASH resolution (RR 5.86; 95 %CI 1.15–29.94), and reduction ≥30 % in hepatic fat fraction by MRI-PDFF (RR 3.14; 95 %CI 1.44–6.85). There were no significant differences in fibrosis improvement ≥1 stage without worsening of MASH (RR 1.48; 95 %CI 0.93–2.35), and overall AEs (RR 1.02; 95 %CI 0.95–1.11) between the groups. Subgroup analysis by fibrosis stage and Aldafermin dosage showed consistent results, and meta-regression analysis by dosage showed a dose-dependent improvement for the outcome of ≥30 % reduction in hepatic fat fraction by MRI-PDFF.

Conclusion

In conclusion, Aldafermin improved MASH resolution without worsening fibrosis, enhanced the composite of fibrosis improvement and MASH resolution, reduced hepatic fat fraction by MRI-PDFF, and was safe for treating patients with biopsy-confirmed MASH compared to placebo.

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背景我们旨在评估阿尔达非明治疗活检证实的代谢功能障碍相关性脂肪性肝炎（MASH）患者的疗效和安全性：我们检索了PubMed、Embase和Cochrane图书馆截至2024年12月8日的随机对照试验（RCT），这些试验对Aldafermin和安慰剂治疗MASH患者进行了比较。采用随机效应模型对二元结局的风险比 (RR) 和 95% 置信区间 (CI) 进行了汇总。此外，我们还按纤维化分期和阿尔达非明剂量进行了亚组分析，并假设阿尔达非明剂量为协变量进行了元回归分析：结果：我们纳入了 4 项 RCT，涉及 491 名患者。与安慰剂相比，Aldafermin具有更高的MASH缓解而纤维化不恶化的概率（RR 3.04；95%CI 1.12-8.28）、纤维化改善和MASH缓解的复合概率（RR 5.86；95%CI 1.15-29.94）以及通过MRI-PDFF使肝脏脂肪分数减少≥30%的概率（RR 3.14；95%CI 1.44-6.85）。在纤维化改善≥1期且MASH不恶化（RR 1.48；95%CI 0.93-2.35）和总体AEs（RR 1.02；95%CI 0.95-1.11）方面，两组间无明显差异。按纤维化分期和Aldafermin剂量进行的亚组分析显示出一致的结果，按剂量进行的元回归分析显示，MRI-PDFF显示肝脏脂肪分数减少≥30%的结果具有剂量依赖性：总之，与安慰剂相比，Aldafermin能改善MASH的缓解而不加重纤维化，提高纤维化改善和MASH缓解的综合效果，通过MRI-PDFF降低肝脏脂肪率，并且治疗活检证实的MASH患者是安全的。

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来源期刊

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.