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P202. Ipilimumab colitis: a GETAID multicentric study

L. Marthey1, C. Mateus2, M. Nachury3, S. Nancey4, F. Grange5, C. Zallot6, J.F. Rahier7, M. Bourdier de Beauregard8, L. Peyrin-Biroulet6, L. Mortier9, C. Robert2, F. Carbonnel10, 1Beclere Hospital, Gastroenterology, Clamart, France, 2Gustave Roussy Institute, Dermatology, Villejuif, France, 3Huriez Hospital, Gastroenterology, Lille, France, 4Lyon Sud Hospital, Gastroenterology, Pierre Benite, France, 5Debre Hospital, Dermatology, Reims, France, 6Brabois Hospital, Gastroenterology, Vandoeuvre les Nancy, France, 7Mont Godinne Hospital, Gastroenterology, Yvoir, Belgium, 8Minjoz Hospital, Gastroenterology, Besançon, France, 9Huriez Hospital, Dermatology, Lille, France, 10Bicetre Hospital, Gastroenterology, Kremlin-Bicetre, France

Background

Ipilimumab (IPI), an anti-CTLA4 monoclonal antibody, induces proliferation and activation of T-cells and is an anti-tumoral treatment, particularly in melanoma. It provokes an immune-mediated colitis similar with IBD in 20% of patients. IPI colitis (IC) may provide clues to the immune mechanisms and treatment of IBD. The aim of this study was to provide a detailed description of IC.

Methods

From June 2011 to May 2013, patients treated for IC in GETAID centers were studied retrospectively. IPI was infused prior IC, colitis was endoscopically proven, infectious colitis was ruled out by stools searches. Quantitative variables are expressed as median [range].

Results

26 patients (16 males) aged 60.5 [23–80] were studied. 24 had melanoma, 2 had prostate carcinoma. 6 had immune disorders prior to IPI infusions. The median number of IPI infusions was 3 [1–8], the delay between first IPI infusion and IC was 36 days [4–91]. Symptoms of IC were: diarrhea (92%), abdominal pain (80%), hematochezia (56%), vomiting (44%), and fever (40%). Median body weight loss was 6% [0–18%]. 1 patient had an oral ulceration, 2 had ano-perineal lesion, 4 had extra intestinal manifestations. 2 patients had intra-abdominal abscess and 3 had colonic perforation. CRP was 93 mg/l [5–622], albumin was 26 g/l [14–39], faecal calprotectin was 4208 mg/g [932–12900]. No patient had serum ASCA or ANCA. All patients had partial colonoscopy and 19 had ileocolonoscopy: 16% had ileitis, 57% pancolitis; 77% had ulcerations, 57% had patchy distribution. Histopathological analysis of endoscopic biopsies showed mucosal inflammation with mononuclear cells infiltration, crypt dystrophy, cryptic abscesses and mucosal ulcerations. 3 patients had granuloma. 23 patients received steroids at a dose of 60 mg [16–120]. Complete or partial responses occurred in 8 and 11 patients, respectively. 9 responders relapsed: 2 had a new course of steroids and 5 received infliximab (IFX). 3 primary non responders to corticosteroids were prescribed IFX; 1 achieved remission and 2 had partial response. Overall, 8/26 patients (31%) required IFX. 3 patients (12%) underwent colectomy (1 subtotal, 2 partial) because of perforation and had severe post-operative complications. No patient died of IC.

Conclusion

IC appears to be similar with Crohn's disease: patchy distribution, ileal and perianal involvement, granuloma. It has an accelerated and severe course: only 36 days between IPI infusion and symptoms, 31% need IFX and 12% have perforation. Close collaboration between IPI prescriptors and gastroenterologists is required for optimal management of IC.