Nivolumab-Induced Colitis Treated by Infliximab

Abstract

A 51-year-old man was admitted to our institution for abdominal pain and bloody diarrhea. The patient had been diagnosed as having uveal melanoma of the right eye 17 years previously, which had been treated by enucleation and radiotherapy. Because of the recurrent melanoma in the right orbit with multiple metastases in the liver and stomach, immunotherapy with triweekly infusion of nivolumab (200 mg, 2 mg/kg) was started. After the fourth infusion of nivolumab, he manifested abdominal pain and bloody diarrhea. The laboratory test results were as follows: white blood cell count, 5370/mL; hemoglobin level, 15.5 g/dL; platelet count, 180,000/ mm 3 ; serum protein level, 6.7 g/dL; albumin level, 4.3 g/dL; and C-reactive protein level, 3.3 mg/L (normal, 0-1.4 mg/L). The computed tomography scan showed thickening of the sigmoid colon and the rectum. Colonoscopy showed reddish, edematous mucosa with increased mucous exudate and loss of normal vascularity throughout the entire colorectum ( Figures A and B).

The characteristics of nivolumab-induced colitis: an evaluation of three cases and a literature review

“…1d). According to recent reports [7–10], similar findings were observed following treatment with nivolumab. We observed the same clinical findings, which included continuous mucosal inflammation, in the patients described in this study (Table 1).…”

“…As neither is a characteristic finding, it is difficult to differentiate based on pathological findings. However, Yanai et al reported that prominent apoptosis in the colorectal epithelium appears to be a characteristic histological finding of nivolumab-induced colitis [10]. To clarify the differences between UC and nivolumab-induced colitis, further evidence derived from reported cases is needed.…”

“…The potential risk of gastrointestinal perforation should be considered for patients in emergency situations. Infliximab therapy can be considered for patients who do not respond to steroids [10, 23] but cannot be used when gastrointestinal perforation or sepsis is observed.…”

“…These findings suggest that colitis is less frequent during treatment with PD-1/PD-L1 inhibitors than during treatment with CTLA-4 inhibitors [3, 5, 6]. Moreover, little is known about the endoscopic features of PD-1/PD-L1 inhibitors except for what has been documented in the four case reports published to date [7–10]. In this report, we describe three cases of anti-PD-1 antibody nivolumab cessation because of severe colitis and consider the clinical features of this condition.…”

Severe Gastritis after Administration of Nivolumab and Ipilimumab

“…Notably, enterocolitis has been reported in up to approximately 8$ of patients who have received ipilimumab [5]. In contrast, nivolumab-induced colitis is rare, and only 2 cases have been reported to date [6, 7]. As ipilimumab is a monoclonal antibody against CTLA-4, which negatively regulates T-cell activation, ipilimumab-induced colitis might result from an increase in cytotoxic CD8+ T cells relative to regulatory FoxP3+ T cells in the colon [8].…”