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INFLIXIMAB FOR ANTI-CTLA 4 ANTIBODY INDUCED COLITIS
D Krygier, N Chatur
Division of Gastroenterology, UBC, Vancouver, British Columbia
BACKGROUND: Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) is an inhibitor of T-cell activation and its blockade enhances antitumor reponses. Clinical trials of anti-CTLA 4 antibody in advanced melanoma have shown objective tumor response. Patients who receive this therapy often develop autoimmune toxicities, most commonly enterocolitis which occurs in up to 21% of patients. The majority of cases have responded to high dose corticosteroids and a very small number of steroid-refractory cases have responded to infliximab.
CASE: We report the case of a 62 year old Caucasian female diagnosed in 2005 with a malignant melanoma of the right leg. She underwent right inguinal lymph node dissection shortly thereafter and was found to have positive regional lymph nodes and metastatic deposits in the subcutaneous tissue of the chest and abdomen. In April 2007, she was enrolled in a phase 2 clinical trial and received a cycle of anti-CTLA 4 antibody (ticilimumab). She remained clinically well and in July 2007 she received a second cycle of the antibody. In late July, she developed profuse watery diarrhea with up to 20 loose, non-bloody stools per day associated with abdominal cramping and nausea. This resulted in hospital admission and initiation of prednisone and asacol on August 28, 2007 with minimal symptomatic improvement. Five days later she was transferred to a tertiary care hospital and placed on intravenous methylprednisilone 40mg twice daily. TPN was initiated. Stool samples revealed no evidence of infection and she continued to report 5-18 loose stools daily. Thirteen days after hospital admission she underwent colonoscopy after developing rectal bleeding with a 30 g/L decrease in her hemoglobin. Colonoscopy revealed diffuse hemorrhagic pancolitis with ulceration and cobblestoning in the transverse colon. The terminal ileum and rectum appeared normal. Colonic biopsies revealed mild chronic active colitis with crypt architectural distortion and no granulomas. Biopsies from the terminal ileum demonstrated one focus of mild acute cryptitis. She continued to experience frequent, loose, bloody stools despite high dose corticosteroids and required intermittent transfusions of packed red blood cells. Twenty-four days after hospital admission she received an intravenous infusion of 5mg/kg of infliximab and within 2 days noted significant improvement. Her stool frequency decreased to 3 formed, non-bloody bowel movements daily and she began to eat well enough to permit discontinuation of TPN and subsequent discharge home. Sigmoidoscopy with biopsies prior to discharge revealed complete mucosal healing.
CONCLUSIONS: Steroid-refractory anti-CTLA 4 antibody induced colitis appears responsive to a single infusion of 5mg/kg of infliximab.