Zaidi Maadeha H, Haider Zaroon, Sadia Fnu, Tayyab Muhammad, Tariq Muhammad Naveed, Ans Hasaan H, Javaid Muhammad Bilal, Khan Ahmad, Ahmad Muhammad Hassan, Rasheed Rahman, Jafar Uzair, Cheema Huzaifa Ahmad, Alsubari Asma'a Munasar Ali, Shahzil Muhammad, Rashad Essam, Ullah Awan Rehmat, Ali Hassam, Jalal Prasun K
Department of Medicine Fudan University Shanghai China.
Department of Medicine CMH Lahore Medical College Lahore Pakistan.
JGH Open. 2025 Jun 6;9(6):e70196. doi: 10.1002/jgh3.70196. eCollection 2025 Jun.
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.
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.
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.
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.
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）等传统药物无反应的原发性胆汁性胆管炎（PBC）患者。本荟萃分析旨在评估PPAR激动剂（包括贝特类药物和选择性PPAR激动剂）对UDCA无反应的原发性胆汁性胆管炎患者生化反应和安全性结局的安全性和有效性。
我们检索了多个电子数据库，包括MEDLINE（通过PubMed）、Embase、Cochrane图书馆和ClinicalTrials.gov，以检索比较PPAR激动剂与安慰剂治疗PBC患者的随机对照试验（RCT）。
我们的荟萃分析纳入了12项涉及973例患者的RCT，结果显示，与安慰剂相比，PPAR激动剂（包括贝特类药物和选择性PPAR激动剂）从基线到随访显著降低了平均碱性磷酸酶（ALP）水平。它们还增加了具有复合生化反应的患者数量（RR 5.51；95%CI：2.80，10.86），并使ALP水平正常化，同时降低了瘙痒数字评分量表（NRS）评分和瘙痒发生率。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，需要进行更大样本量、更长随访时间且以患者为中心结局为重点的进一步研究。此外，探索联合治疗和机制见解将有助于我们充分实现PPAR激动剂在PBC中的治疗潜力。
