Ipilimumab-induced colitis: experience from a tertiary referral center. (July 2016)

• Record Type: Journal Article
• Authors: O'Connor, Anthony; Marples, Maria; Mulatero, Clive; Hamlin, John; Ford, Alexander C.
• Is Part Of: Therapeutic advances in gastroenterology. Volume 9:Number 4(2016:Jul.)
• Page Start: 457
• Page End: 462
• Publication Date: 2016-07
• Subjects: colitis -- diarrhoea -- infliximab -- ipilimumab -- melanoma; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Liver -- Diseases -- Treatment -- Periodicals; Pharmacology -- Periodicals; Gastroenterology -- Periodicals; Gastrointestinal Diseases -- therapy -- Periodicals; Liver Diseases -- therapy -- Periodicals; Pharmacology -- Periodicals; Gastroentérologie -- Périodiques; Appareil digestif -- Maladies -- Traitement -- Périodiques; Tractus gastro-intestinal -- Maladies -- Traitement -- Périodiques; Hépatologie -- Périodiques; Foie -- Maladies -- Périodiques; Pharmacologie -- Périodiques; 616.3005
• DOI: 10.1177/1756283X16646709
• Languages: English
• ISSNs: 1756-283X

Abstract

Background: Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody used for the treatment of malignant melanoma. It can cause immune-mediated inflammatory adverse events, including diarrhoea and even intestinal perforation or death in clinical trials but there is a dearth of data on postmarketing outcomes. Methods: A total of 546 patients attending for treatment of metastatic melanoma between 1 January 2009 and 31 August 2015 were identified by interrogation of the oncology database. A total of 83 of these patients received ipilimumab. Clinical information was extracted from chart reviews, endoscopy and radiology reports, and prescription data. Results: A total of 83 patients received ipilimumab. Only 19.3% ( n = 16) of patients developed a diarrhoeal illness not attributable to other causes. The median grade of diarrhoea among included patients was 2 (range 1–4). In two cases, diarrhoea settled spontaneously without any specific treatment. A total of 87.5% of patients received antidiarrhoeal agents such as loperamide or codeine. These resolved symptoms in all patients with grade 1 diarrhoea. For other treatment, 50% patients received systemic glucocorticosteroids and 31.3% required infliximab. Infliximab resolved symptoms in 100% of cases compared with 50% for systemic glucocorticosteroids. Conclusions: The rate of diarrhoea related to ipilimumab in real-world practice is substantial, but below the range observed in data from RCTs. Grade 1 colitis can usually be managed symptomatically, without recourse to stopping ipilimumab. When diarrhoea was grade 2 or above, results from glucocorticosteroids use proved disappointing; but infliximab has been shown to work well. Further research is required into the earlier use of infliximab as an effective treatment for ipilimumab-induced diarrhoea.