Lack of efficacy of infliximab in the treatment of primary sclerosing cholangitis in inflammatory bowel diseases in childhood Sabrina Cardile, Manila Candusso, Bronislava Papadatou, Fiammetta Bracci, Daniela Knafelz and Giuliano Torre, Hepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children’s Hospital, Rome, Italy Correspondence to Sabrina Cardile, MD, Hepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, Rome 00165, Italy Tel: +39 06 6859 2329; fax: +39 06 6859 3889; e-mail: sabrina.cardile@opbg.net Received 23 November 2016 Accepted 5 January 2017 Involvement of the liver and biliary systems represents a potential risk in inflammatory bowel diseases (IBDs), and primary sclerosing cholangitis (PSC) is the entity most expressed, with an incidence rate of 6.4–7.8% in children. The treatment of these patients is controversial and there are no pre-established therapeutic algorithms [1]. Biologic drugs are widely used in the management of pediatric patients with IBDs, but their effectiveness on the associated PSC is unknown, and only anecdotal cases have been reported in the literature [2,3]. Franceschet et al. [4] conducted a study in a population of IBD and PSC-associated patients (49 patients; mean age 29.2 ± 14.8 years) in which they used biologic agents [infliximab (IFX), adalimumab, and rituximab] in five patients, observing an improvement in intestinal disease and in liver function tests, although the reported data are not clear. In 2015, we completed a retrospective study (14 years) on pediatric patients affected by IBD and PSC (23 patients), con- sidering the ones treated with IFX for their intestinal disease, to assess its clinical effectiveness in both IBD and PCS. Of the 23 patients, four (17.4%, three male), all of them with ulcerative colitis, were treated with IFX with the following schedule: induction with 5 mg/kg (intravenouslly) at weeks 0, 2, and 6, followed by maintenance treatment with 5 mg/kg (intrave- nouslly) every 8 weeks. Age at diagnosis of IBD was 7.21 ± 5.32 years with a follow-up of 91.05 ± 69.03 months. IFX was started after 5.72 years from the diagnosis of ulcerative colitis (range: 0.54–9.92 years), or for steroid-resistant/depen- dent or severe intestinal disease. The IFX was discontinued in all patients after 0.53 ± 0.20 months (VI–IV infusion): in two patients because of poor control of the hepatobiliary disease [alanine aminotransferase 5.4 × upper limit of normal (ULN), aspartate aminotransferase 4.3 × ULN, γ-glutamyltransferase 9.8 × ULN] with necessity to change therapy; in one patient because of adverse reaction (flushing of the face, skin rash, tachycardia, and fainting); and in one patient because of relapse of severe intestinal disease, with contextual evidence of lack of control of the hepatobiliary disease. In all patients, we found an increase in cytolysis and cholestasis during IFX therapy (Fig. 1). We also noticed in these patients poor control of intestinal disease with 1–2 episodes of mild–moderate intestinal relapses per patient, and need to start steroids and antibiotics repeated over time, with persistent use of other immunosuppressants in two patients (azathioprine). In one patient relapse of severe intestinal disease required colectomy. Hepatobiliary involve- ment in IBDs, in particular in pediatric patients, still remains a challenge for clinicians because of the difficulty to diagnose and manage both diseases with current drugs in use. Our limited experience shows that IFX is not effective in the control of PSC- associated with IBD in pediatric patients, as it does not change its clinical course or outcome. Increasing awareness of the underlying pathogenic mechanisms could open up new fron- tiers for controlling inflammation and progression of these diseases, and other biological drugs with different mechanisms of action (e.g. vedolizumab) could represent the future in the treatment of these patients. Acknowledgements Conflicts of interest There are no conflicts of interest. References 1 Turner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, et al. European Crohn’s and Colitis Organization; European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr 2012; 55:340–361. 2 Siemanowski B, Regueiro M. Efficacy of infliximab for extraintestinal manifestations of inflammatory bowel disease. Curr Treat Options Gastroenterol 2007; 10:178–184. 3 Hommes DW, Erkelens W, Ponsioen C, Stokkers P, Rauws E, van der Spek M, et al. A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis. J Clin Gastroenterol 2008; 42:522–526. 4 Franceschet I, Cazzagon N, Del Ross T, D’Incà R, Buja A, Floreani A. Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options. Eur J Gastroenterol Hepatol 2016; 28:508–513. DOI: 10.1097/MEG.0000000000000847 Start IFX Stop IFX Fig. 1. Average parameters pre and post-IFX of our pediatric population. ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyltransferase; IFX, infliximab. European Journal of Gastroenterology & Hepatology 2017, 29:736–737 ’ Letters to the Editor 0954-691X Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. 736 Copyright r 2017 Wolters Kluwer Health, Inc. All rights reserved.