title: The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children.
abstract: BACKGROUND
  Management of refractory inflammatory bowel disease (IBD) in children is challenging and once response to conventional medical therapy deviates from the expected, options are often limited. Sirolimus is commonly used in post-transplantation management and is used sparsely as rescue therapy in refractory Crohn's disease. In the present study, we report the efficacy of sirolimus as an adjuvant immunosuppressive therapy in a retrospective case review of a selected group of IBD children who were refractory to the conventional treatments.
  
  
  METHODS
  Medical records of children with refractory IBD unresponsive to conventional therapy and started on sirolimus between 2006 and 2012 were retrospectively reviewed. Clinical response, through Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI), as well as intestinal inflammation, through specific histological scores, was evaluated.
  
  
  RESULTS
  The records of 14 patients were analyzed. Eleven of them had ulcerative colitis (UC) and 3 Crohn's disease (CD); mean age at diagnosis was 9.1 years (standard deviation 3.8). Of UC patients, 5 (45%) achieved clinical remission and 2 (18%) showed clinical response. All CD patients went into clinical remission. Mucosal healing was achieved by 5 children (45%) with UC and 2 (67%) with CD patients. One child with ulcerative colitis was weaned off adalimumab, while 2 children with CD were weaned off prednisolone and methotrexate successfully.
  
  
  CONCLUSIONS
  Our data provide evidence that sirolimus seems to be effective as rescue therapy in a subgroup of children with severe IBD refractory to conventional therapies by inducing both clinical remission and mucosal healing.
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom. Electronic address: mohamed.mutalib@gosh.nhs.uk.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mutalib
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Borrelli
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Blackstock
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom.
authors.forename: Fevronia
authors.initials: F
authors.lastname: Kiparissi
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom.
authors.forename: Mamoun
authors.initials: M
authors.lastname: Elawad
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Paediatric Gastroenterology, Great Ormond Street Hospital for Sick Children NHS Foundation Trust, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Lindley
mesh_terms: D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Crohn's disease; IBD; Inflammatory bowel disease; Sirolimus; Ulcerative colitis