It may be associated with a diffuse and continuous inflammation of the colon without small intestinal involvement

It may be associated with a diffuse and continuous inflammation of the colon without small intestinal involvement. responded. Six patients underwent colectomy (perforation = 5; toxic megacolon = 1); one of them died postoperatively. Four patients had a Rabbit Polyclonal to p90 RSK persistent enterocolitis at follow-up colonoscopy. Patients with enterocolitis were more frequently prescribed NSAIDs compared with patients without enterocolitis (31 vs 5%, = 0.003). Conclusions: Ipilimumab and tremelimumab may induce a severe and extensive form of inflammatory bowel disease. Rapid escalation to infliximab should be advocated in patients who do not respond to steroids. Patients treated with anti-CTLA-4 should be advised to avoid NSAIDs. toxin), were excluded. Ipilimumab was administered by intravenous infusion every 3 weeks during an induction phase, at a dose of 3 or 10mg/kg of body weight. Patients could continue ipilimumab infusions with a maintenance treatment every 12 weeks in case of tumour response or stable disease. Tremelimumab was administered by intravenous infusion every 4 weeks, at a dose of 3 or 10mg/kg of body weight. Socio-demographic, clinical, biological and endoscopic data were recorded using pre-specified forms. Gastric, duodenal and colonic endoscopic biopsies and colectomy specimens of patients referred from Gustave Roussy to Bictre Hospital were reviewed by a single pathologist (C. Mussini). We classified anti-CTLA-4 enterocolitis into 3 groups based on clinical management of the enterocolitis: (1) those who had a spontaneous favourable outcome; (2) those who required steroids; and (3) those who required immediate colectomy. For each of these groups, we noted the short- and long-term outcomes of the enterocolitis. We also recorded the effects of anti-CTLA-4 re-infusions. Finally, the association between clinical factors and occurrence of enterocolitis was studied. For this purpose, patients with melanoma treated by ipilimumab who had enterocolitis were compared with a control group of patients with Flupirtine maleate melanoma treated with ipilimumab at Gustave Roussy and who did not Flupirtine maleate have enterocolitis. We also performed a sensitivity analysis restricted to the patients treated at Gustave Roussy. For this purpose, we compared patients with melanoma and enterocolitis treated with ipilimumab at Gustave Roussy with a control group of patients with melanoma and no enterocolitis, treated with ipilimumab at Gustave Roussy. Quantitative data are described with the median (range) and qualitative data are described as number and percentage. Quantitative data were compared using Student’s test and qualitative data using the 2 2 test. The study was submitted to the ethics committee of Paris-Ile de France VII. This committee stated that there was no ethical issue related to this study. 3. Results Seven centres participated in this study. Thirty-nine patients with anti-CTLA-4 enterocolitis were reported. The baseline characteristics of these patients are summarized in Table 1. Most patients received ipilimumab for melanoma; none of them received any concomitant chemotherapy or immunosuppressive treatment. Two patients (5%) received tremelimumab and gefitinib for non-small-cell lung carcinoma. Eighteen patients received anti-CTLA-4 at a dose of 3mg/kg, five received a dose of 10mg/kg and Flupirtine maleate 16 received either 3 or 10mg/kg in blinded trials (GEFTREM trial “type”:”clinical-trial”,”attrs”:”text”:”NCT02040064″,”term_id”:”NCT02040064″NCT02040064; BMS CA184-169 trial “type”:”clinical-trial”,”attrs”:”text”:”NCT01515189″,”term_id”:”NCT01515189″NCT01515189; Ipilimumab + Stereotactic Radiotherapy EUDRACT 2012-000852-32; MelIpiRx trial EUDRACT 2010-020317-93; EORTC 18071 trial EUDRACT 2007-001974-10). The median number of anti-CTLA-4 infusions was 2 (1C8). Eight patients (20.5%) had a personal history of autoimmune or inflammatory disorders prior to anti-CTLA-4 infusion. One patient (2.5%) had a family history of Crohns disease. Table 1. Characteristics of patients with anti-CTLA-4-induced enterocolitis (= 39). = 5), hypophysitis (= 2), hepatitis (= 1), nephritis (= 1), pericarditis (= 1), pancreatitis (= 1), thyroiditis (= 1) and pyoderma gangrenosum (= 1). Five patients had a colon perforation, of.