P313. The use of sirolimus for refractory inflammatory bowel disease: A single centre experience
M. Mutalib, S. Blackstock, S. Chadokufa, B. Huggett, N. Shah, M. Elawad, F. Kiparissi, K. Lindley, Great Ormond Street Hospital, Paediatric Gastroenterology, London, United Kingdom
Refractory inflammatory bowel disease (IBD) in children is challenging. The primary outcome of this study was to assess the therapeutic efficacy of Sirolimus in children with refractory IBD. Secondary outcomes included Sirolimus tolerance and duration of therapy.
We retrospectively reviewed medical and nursing records of all patients with IBD on Sirolimus (23 patients) between 2006 and 2012. Clinical response was assessed by PUCAI or PCDAI. All patients had an activity index at baseline and 3 months after induction of Sirolimus. Endoscopic and histological findings before starting Sirolimus were compared to the next available endoscopy at least 3 months later. A total of eight cases were excluded, 6 due to incomplete data and 2 due to short treatment time (less than one month).
15 cases had severe refractory IBD, 4 were Crohn's disease (CD), 11 were Ulcerative colitis (UC), 9 were males. The mean age of onset of disease was 8.7 years. The mean number of years after diagnosis until induction with Sirolimus was 3.1 years. The oral daily dose range was between 0.5 mg and 5 mg with a targeted serum trough level of 5–10 ng/ml. The mean trough level was 7.5 ng/ml. 16 patients had failed standard medical therapy and all stayed on conventional treatment while on Sirolimus. 15 patients had received steroids, thiopurines, 5-ASAs, 13 infliximab, 8 adalimumab, 5 methotrexate, 2 tacrolimus and two basiliximab prior to starting Sirolimus. 8/11 patients with UC had a response shown by improvement in their PUCAI score at 3 months, 3/11 had no response. Of the patients who responded 2 achieved remission with concomitant administration of Basiliximab, one was started on Mycophenalate while the fourth child required complete gut rest and parenteral nutrition for 6 weeks. 3/8 responders and 2/3 non responders went on to have Colectomys. 3 CD patients had clinical response to their PCDAI scores. 1 CD patient was successfully weaned off prednisolone, 1 off methotrexate. 5/11 patients with UC achieved histological mucosal healing while 4 patients still had some disease activity. Of the CD patients one achieved mucosal healing while 3 demonstrated ongoing inflammation, No side-effects were reported to Sirolimus in the included patients.
Our study was limited by its retrospective design; however we demonstrated clinical and histological response to Sirolimus in children with refractory IBD who failed conventional medical therapy. With careful patient selection, Sirolimus (as an adjunct immunosuppressant) appears to be safe and effective medical therapy to be considered in children with severe refractory IBD.