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
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
Affiliations
Maadeha H. Zaidi
Department of Medicine Fudan University Shanghai China
Zaroon Haider
Department of Medicine CMH Lahore Medical College Lahore Pakistan
FNU Sadia
Department of Medicine Jinnah Sindh Medical University Karachi Pakistan
Muhammad Tayyab
Department of Medicine Faisalabad Medical University Faisalabad Pakistan
Muhammad Naveed Tariq
Department of Medicine Khyber Medical University Peshawar Pakistan
Hasaan H. Ans
Department of Medicine FMH College of Medicine & Dentistry Lahore Pakistan
Muhammad Bilal Javaid
Department of Medicine CMH Lahore Medical College Lahore Pakistan
Ahmad Khan
Department of Medicine Khyber Medical University Peshawar Pakistan
Muhammad Hassan Ahmad
Department of Medicine Allama Iqbal Medical College Lahore Pakistan
Rahman Rasheed
Department of Medicine Bahira University of Health Sciences Karachi Pakistan
Uzair Jafar
Department of Medicine King Edward Medical University Lahore Pakistan
Huzaifa Ahmad Cheema
Department of Medicine King Edward Medical University Lahore Pakistan
Asma'a Munasar Ali Alsubari
Faculty of Medicine Sana'a University Sana'a Yemen
Muhammad Shahzil
Department of Internal Medicine Milton S Hershey Medical Center, The Pennsylvania State University Hershey Pennsylvania USA
Essam Rashad
Department of Internal Medicine Parkview Regional Medical Center Fort Wayne Indiana USA
Rehmat Ullah Awan
Department of Gastroenterology and Hepatology West Virginia University Morgantown West Virginia USA
Hassam Ali
Department of Gastroenterology, Hepatology & Nutrition ECU Health Medical Center/Brody School of Medicine Greenville North Carolina USA
Prasun K. Jalal
Section of Gastroenterology and Hepatology, Department of Medicine Baylor College of Medicine Houston Texas USA
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.
