Ipilimumab and Nivolumab Induced Steroid-Refractory Colitis Treated With Infliximab

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Introduction We report a case of severe steroid-refractory colitis induced by the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab in a patient with metastatic renal cell carcinoma, and its resolution after treatment with Infliximab. Case Description A 63 year male with metastatic renal carcinoma presents to the hospital with a several day history of diarrhea. The patient had received his third combination infusion of Ipilimumab and Nivolumab and developed severe watery non-bloody diarrhea the same day. He continued to have upwards of 10 watery bowel movements and presented to the hospital where he was found to be severely dehydrated and in acute renal failure (Table 1). He was started on broad spectrum antibiotics, IV fluids and electrolyte replenishment. An infectious workup for diarrhea was performed which was negative (Table 2). His antibiotics were discontinued and the patient was started on high dose IV steroids but his diarrhea persisted. Ten days after receiving his treatment the Gastroenterology service was consulted. The patient had been on high dose steroids, lomotil and loperamide without relief or resolution. He was placed on a trial of mesalamine and subcutaneous octreotide. Given the temporal relationship between the onset of his symptoms and his immune treatment, an immune-mediated colitis was suspected. The patient received a colonoscopy the next day with no endoscopic evidence of disease. Random biopsies showed mild colitis, and testing for HSV and CMV were negative. After testing for hepatitis B and tuberculosis, the patient received an Infliximab 5 mg/kg infusion and noted improvement later the same day. The following day the patient had complete resolution of his diarrhea without any bowel movements. His metabolic derangements normalized and all medications were gradually discontinued. He was discharged with a steroid taper and instructed to follow up as an outpatient. Discussion Ipilimumab has been associated with severe immune-mediated colitis refractory to high dose steroids. Infliximab is thought to work in these cases by opposing the activation of T cells by CTLA-4 antibodies by suppressing the pro-inflammatory cytokines IL 1 and IL6. Given the increasing use of immune therapy in a variety of cancers, it is important that gastroenterologists be familiar with their gastrointestinal side effects as well as their management.1616_A Figure 1 No Caption available.1616_B Figure 2 No Caption available.

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