Kamrul-Hasan Abul Bashar Mohammad, Borozan Sanja, Jena Sweekruti, Nagendra Lakshmi, Dutta Deep, Bhattacharya Saptarshi, Islam Md Saiful, Pappachan Joseph M
Department of Endocrinology, Mymensingh Medical College, Mymensingh 2200, Bangladesh.
Department of Endocrinology, Clinical Centre of Montenegro, Podgorica 81000, Montenegro.
World J Gastrointest Pharmacol Ther. 2025 Sep 5;16(3):110709. doi: 10.4292/wjgpt.v16.i3.110709.
Efruxifermin (EFX), a fibroblast growth factor 21 analogue, has demonstrated the potential to improve liver fat and markers of liver injury, fibrosis, and key metabolic biomarkers in individuals with metabolic dysfunction-associated steatohepatitis (MASH) in phase 2 clinical trials.
To summarize the safety and effectiveness of EFX in managing MASH.
Electronic databases and registries were systematically searched from their inception to May 15, 2025, for randomized-controlled trials (RCTs) that included EFX in the intervention arm and placebo in the control arm in individuals with MASH. The primary outcome was the safety of EFX, while additional outcomes included its efficacy in altering hepatic and metabolic parameters. Meta-analyses were conducted using the RevMan web computer program with the random-effects model.
Four phase 2 RCTs (five reports), mostly with low risk of bias, involving 450 subjects, were analyzed. Compared to the placebo, EFX 50 mg was associated with higher risks of treatment-emergent adverse events (TEAEs) [risk ratio (RR) = 1.05], TEAEs leading to discontinuation (RR = 3.05), nausea (RR = 1.78), and diarrhea (RR = 1.9). EFX 28 mg increased risks of vomiting (RR = 2.17) and frequent bowel movements (RR = 8.98). Both doses of EFX were associated with higher risks of drug-related TEAEs (28 mg: RR = 1.45; 50 mg: RR = 1.67) and increased appetite (28 mg: RR = 3.16; 50 mg: RR = 5.66). EFX (28 and 50 mg) and placebo exhibited identical risks for severe TEAEs, serious AEs, abdominal pain, fatigue, headache, injection site erythema, and injection site reactions. EFX (28 and 50 mg) was associated with improvements in hepatic safety outcomes, including liver enzymes and urate levels. EFX outperformed the placebo in both relative and absolute reductions in hepatic fat fraction. Reductions in enhanced liver fibrosis score, Pro-C3, and liver stiffness were also more robust with EFX. EFX was superior in terms of MASH resolution and improvement in fibrosis stage, MASH resolution and no worsening of the fibrosis stage, and fibrosis regression by ≥ 1 stage and no worsening in steatohepatitis. Furthermore, EFX also improved metabolic parameters, including reductions in HbA1c and insulin resistance, as well as improvements in adiponectin and lipid parameters.
EFX demonstrates promising dual efficacy on liver histology and metabolic markers in MASH. However, gastrointestinal side effects and the need for parenteral administration require caution. Long-term data are still necessary to fully evaluate safety and long-term effectiveness.
艾弗西费明（EFX）是一种成纤维细胞生长因子21类似物，在2期临床试验中已显示出改善代谢功能障碍相关脂肪性肝炎（MASH）患者肝脏脂肪、肝损伤标志物、纤维化及关键代谢生物标志物的潜力。
总结艾弗西费明治疗MASH的安全性和有效性。
系统检索电子数据库和注册库，检索时间从建库至2025年5月15日，查找在干预组中使用艾弗西费明、对照组中使用安慰剂的MASH患者的随机对照试验（RCT）。主要结局是艾弗西费明的安全性，其他结局包括其改变肝脏和代谢参数的疗效。使用RevMan网络计算机程序采用随机效应模型进行荟萃分析。
分析了4项2期RCT（5份报告），大多偏倚风险较低，涉及450名受试者。与安慰剂相比，50mg艾弗西费明出现治疗期间出现的不良事件（TEAE）的风险更高[风险比（RR）=1.05]，因TEAE导致停药的风险更高（RR = 3.05），恶心（RR = 1.78）和腹泻（RR = 1.9）。28mg艾弗西费明增加了呕吐（RR = 2.17）和排便次数增多（RR = 8.98）的风险。两种剂量的艾弗西费明出现与药物相关的TEAE的风险均更高（28mg：RR = 1.45；50mg：RR = 1.67），且食欲增加（28mg：RR = 3.16；50mg：RR = 5.66）。艾弗西费明（28mg和50mg）与安慰剂在严重TEAE、严重不良事件、腹痛、疲劳、头痛、注射部位红斑和注射部位反应方面的风险相同。艾弗西费明（28mg和50mg）与肝脏安全性结局的改善相关，包括肝酶和尿酸水平。在肝脏脂肪分数的相对和绝对降低方面，艾弗西费明均优于安慰剂。艾弗西费明在增强肝纤维化评分、前C3和肝脏硬度降低方面也更显著。在MASH缓解和纤维化分期改善、MASH缓解且纤维化分期无恶化以及纤维化消退≥1期且脂肪性肝炎无恶化方面，艾弗西费明更具优势。此外，艾弗西费明还改善了代谢参数，包括糖化血红蛋白和胰岛素抵抗降低，以及脂联素和血脂参数改善。
艾弗西费明在MASH的肝脏组织学和代谢标志物方面显示出有前景的双重疗效。然而，胃肠道副作用和需要胃肠外给药需要谨慎。仍需要长期数据来全面评估安全性和长期有效性。
