Mark R Deneau1, Cara Mack2, Douglas Mogul3, Emily R Perito4, Pamela L Valentino5, Achiya Z Amir6, Matthew DiGuglielmo7, Laura G Draijer8, Wael El-Matary9, Katryn N Furuya10,11, Nitika Gupta12, Jessica T Hochberg13, Simon Horslen14, M Kyle Jensen1, Maureen M Jonas15, Nanda Kerkar16, Bart G P Koot8, Trevor J Laborda1, Christine K Lee15, Kathleen M Loomes17, Mercedes Martinez18, Alexander Miethke19, Tamir Miloh13, Saeed Mohammad20, Nadia Ovchinsky21, Girish Rao22, Amanda Ricciuto23, Pushpa Sathya24, Kathleen B Schwarz3,25, Uzma Shah26, Ruchi Singh19, Bernadette Vitola27, Andréanne Zizzo28, Stephen L Guthery1. 1. University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, UT. 2. University of Colorado School of Medicine, Aurora, CO. 3. Johns Hopkins University, Baltimore, MD. 4. University of California, San Francisco, San Francisco, CA. 5. Yale University School of Medicine, New Haven, CT. 6. The Dana-Dwek Children's Hospital, The Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel. 7. Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE. 8. Amsterdam University Medical Center, Amsterdam, The Netherlands. 9. University of Manitoba, Winnipeg, Manitoba, Canada. 10. Mayo Clinic, Rochester, MN. 11. University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI. 12. Emory University School of Medicine, Atlanta, GA. 13. University of Miami, Miami, FL. 14. University of Washington, Seattle, WA. 15. Boston Children's Hospital and Harvard Medical School, Boston, MA. 16. University of Rochester Medical Center, Rochester, NY. 17. Children's Hospital of Philadelphia, Philadelphia, PA. 18. Columbia University, New York, NY. 19. Cincinnati Children's Hospital Medical Center, Cincinnati, OH. 20. Lurie Children's Hospital, Chicago, IL. 21. Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY. 22. Indiana University, Indianapolis, IN. 23. University of Toronto, Toronto, Ontario, Canada. 24. Memorial University, St. John's, Newfoundland and Labrador, Canada. 25. University of California San Diego, San Diego, CA. 26. Massachusetts General Hospital, Harvard Medical School, Boston, MA. 27. Medical College of Wisconsin, Milwaukee, WI. 28. London Health Sciences Center, Western University, London, Ontario, Canada.
Abstract
BACKGROUND AND AIMS: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.
BACKGROUND AND AIMS: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.
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