Paediatric Primary Sclerosing Cholangitis-Ulcerative colitis. Audit of 2 year outcomes with oral Vancomycin treatment

Abstract

Background: Primary Sclerosing Cholangitis and Ulcerative colitis (PSC-UC) is an emerging phenotype, distinct from other Inflammatory Bowel Disease (IBD) with catastrophic liver and colonic outcomes, in particular higher rates of cancer and premature death. PSC-UC can prove resistant to conventional medical therapies (CMT). Oral Vancomycin Therapy (OVT) is proposed for PSC with uncertain impact on liver outcomes but recently reported efficacy for treatment of the colitis. Last year we reported experience in 17 children, we now report colitis outcomes and lack of emergence of Vancomycin Resistant Enterococcus (VRE) in a larger, well characterised cohort of children with PSCUC receiving OVT with 2 years follow up. Methodology: Children under 18 years of age, attending the Paediatric IBD clinic at Queensland Children's Hospital, a single tertiary centre, from September 2013-December 2020 given OVT for active colitis (elevated Faecal Calprotectin (FC) and/or colonoscopy) in the context of PSC were eligible for review. PSC was confirmed by evidence of cholangiopathy, MRCP and/or Liver biopsy. Only children receiving a minimum 3 months OVT, 50mg/kg/day were included. Main indication was failed Conventional Medical Therapy (CMT). We report induction and maintenance of colitis remission. Deep Remission was defined as Paediatric Ulcerative Colitis Activity Index (PUCAI) < 10, FC < 100 +/-Mucosal Healing (MH) on colonoscopy. Stool for VRE was tested in all patients during therapy. Results: 29 children (mean age 11 years, 1-17 years;18 Male), were given OVT. Median initial treatment duration was 6 months. At 6 months: 2/29 had ongoing active colitis; 27/29 in deep remission, PUCAI < 10, normal FC < 100 (24) and/or colonoscopy (11). Of these 11, 9 had complete MH, 2 near complete MH and received a further 6 months OVT achieving complete MH. At median 12 months, 2 were lost to follow up. 20/27 were in sustained remission, most had ceased OVT and on CMT alone. 18/18 had normal FC and/or 7 had normal colonoscopy. 5/27 had relapsed and all 5 responded clinically and to normal FC after retreatment with OVT. Hence at median of 12 months follow up, 25/27 patients on the OVT program were in deep remission 22 patients had 24 months follow up but 2 had no available data. 15/22 were in complete clinical (PUCAI 0) and deep remission (normal FC,12 and/or colonoscopy, 8) and 10 of these in sustained remission, mostly off OVT. No patient required Colectomy. None developed VRE during this period. Conclusion: OVT in children with UC and confirmed PSC, mostly failing conventional medical therapy, is highly efficacious at inducing and re-inducing deep remission of colitis. No VRE was demonstrated. It is time to study OVT in formal randomized trials which also address pathogenesis to aid in the selection of patients and optimal usage within informed treatment paradigms.L6351748502021-06-08 <br />