Peroxisome Proliferator-Activated Receptor (PPAR) Agonists for Patients With Primary Biliary Cholangitis With Inadequate Response to Ursodeoxycholic Acid (UDCA): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

IF 1.7 Q3 GASTROENTEROLOGY & HEPATOLOGY

JGH Open Pub Date : 2025-06-06 DOI:10.1002/jgh3.70196

Maadeha H. Zaidi, Zaroon Haider, FNU Sadia, Muhammad Tayyab, Muhammad Naveed Tariq, Hasaan H. Ans, Muhammad Bilal Javaid, Ahmad Khan, Muhammad Hassan Ahmad, Rahman Rasheed, Uzair Jafar, Huzaifa Ahmad Cheema, Asma'a Munasar Ali Alsubari, Muhammad Shahzil, Essam Rashad, Rehmat Ullah Awan, Hassam Ali, Prasun K. Jalal

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Abstract

Objective

Peroxisome proliferator-activated receptor (PPAR) agonists are agents used for patients with primary biliary cholangitis (PBC) who do not respond to conventional agents like ursodeoxycholic acid (UDCA). This meta-analysis aimed to assess the safety and efficacy of PPAR agonists, including fibrates and selective PPAR agonists, on biochemical response and safety outcomes in patients with primary biliary cholangitis who were non-responders to UDCA.

Methods

We searched various electronic databases, including MEDLINE (via PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov, to retrieve randomized controlled trials (RCTs) comparing PPAR agonists to placebo in patients with PBC.

Results

Our meta-analysis, including 12 RCTs involving 973 patients, showed that PPAR agonists, including fibrates and selective PPAR agonists, significantly reduce mean alkaline phosphatase (ALP) levels from baseline to follow-up as compared to placebo. They also increase the number of patients with the composite biochemical response (RR 5.51; 95% CI: 2.80, 10.86) and normalize ALP levels with a reduction in pruritus NRS Score and the incidence of pruritus. There was no significant change between the two groups when assessing the mean change in total bilirubin, adverse events, serious adverse events, or mean change in PBC-40 score.

Conclusion

In conclusion, our research underscores the potential of novel PPAR agonists in improving biochemical markers in PBC, particularly in patients unresponsive to UDCA. However, further studies with larger sample sizes, longer follow-up durations, and a focus on patient-centered outcomes are necessary. Additionally, exploring combination therapies and mechanistic insights will help us fully realize the therapeutic potential of PPAR agonists in PBC.

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过氧化物酶体增殖物激活受体（PPAR）激动剂用于对熊去氧胆酸（UDCA）反应不足的原发性胆管炎患者：随机对照试验的系统评价和荟萃分析

目的：过氧化物酶体增殖激活受体（PPAR）激动剂是用于原发性胆管炎（PBC）患者的药物，这些患者对熊去氧胆酸（UDCA）等常规药物没有反应。本荟萃分析旨在评估PPAR激动剂（包括贝特类和选择性PPAR激动剂）对UDCA无反应的原发性胆道炎患者生化反应和安全性结果的安全性和有效性。方法我们检索了各种电子数据库，包括MEDLINE（通过PubMed）、Embase、Cochrane图书馆和ClinicalTrials.gov，检索比较PPAR激动剂和安慰剂治疗PBC患者的随机对照试验（RCTs）。我们的荟萃分析，包括涉及973例患者的12项随机对照试验，显示PPAR激动剂，包括贝特类和选择性PPAR激动剂，与安慰剂相比，从基线到随访期间显著降低平均碱性磷酸酶（ALP）水平。它们还增加了出现复合生化反应的患者数量(RR 5.51；95% CI: 2.80, 10.86)， ALP水平正常化，瘙痒症NRS评分降低，瘙痒症发生率降低。在评估总胆红素的平均变化、不良事件、严重不良事件或PBC-40评分的平均变化时，两组之间没有显著变化。总之，我们的研究强调了新型PPAR激动剂在改善PBC生化指标方面的潜力，特别是在对UDCA无反应的患者中。然而，进一步研究更大的样本量，更长的随访时间，并关注以患者为中心的结果是必要的。此外，探索联合疗法和机制见解将有助于我们充分发挥PPAR激动剂在PBC中的治疗潜力。

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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