Recurrent Checkpoint Inhibitor Colitis Complicated by Treatment Induced Liver Injury Requiring Vedolizumab Therapy

Introduction: With the rise in use of immune checkpoint inhibitors (ICI) in the treatment of cancer, it is important to recognize potential adverse events. Immune-mediated colitis (IMC) occurs in 35% to 50% of patients receiving ICIs with symptom onset typically weeks to months after ICI initiation, including abdominal cramping, rectal bleeding, and most commonly, diarrhea. We present a unique case of IMC refractory to steroids, complicated by DILI attributed to infliximab, and ultimately requiring vedolizumab therapy. Case Description/Methods: A 37-year-old woman with a past medical history of basal cell carcinoma syndrome on cemiplimab, and endocervical adenocarcinoma in situ status-post hysterectomy presented to the emergency department with 4 days of persistent nausea, vomiting, and frequent watery diarrhea. Infectious workup including GI PCR panel, Clostridioides difficile, HIV, CMV, EBV, Quantiferon, VZV, and MMR was unrevealing. Colonoscopy revealed severe diffuse pancolitis with mucosal ulceration. Biopsies showed chronic active colitis with cryptitis and crypt abscesses. Systemic steroids were initiated, and she experienced mild improvement in symptoms. With plateauing of her response, she received an induction dose of infliximab with marked improvement in symptoms. She was discharged with a steroid taper, however, with poor GI followup given controlled symptoms. Two months later, she was readmitted with worsening symptoms and was restarted on steroids. Repeat colonoscopy again showed severe pancolitis, and infliximab therapy was restarted. As she was responding to anti-TNF therapy, her transaminases also increased significantly with a peak ALT of 401. At present, she was transitioned to vedolizumab therapy and is scheduled for future endoscopic evaluation to determine further therapy (Figure 1). Discussion: In our case, given the nonspecific histologic findings on colonoscopy, the diagnosis of IBD was considered; however given the timeline of symptoms, IMC was favored. In steroid refractory IMC, about one-third to two-thirds of patients benefit from infliximab. Treatment with infliximab may cause a rise in serum aminotransferases following 2 to 5 infusions, and have led to hepatitis and liver failure requiring transplantation. To prevent infliximab hepatotoxicity, alternative therapy should be considered when DILI is suspected. Alternative therapy may involve vedolizumab, ustekinumab, tofacitinib, or fecal microbiota transplantation.Figure 1.: Colonoscopy exhibiting pancolitis. A-F respectively: Rectosigmoid junction (A), descending colon (B), splenic flexure (C), transverse colon (D), hepatic flexure (E), ascending colon (F). Histology exhibiting chronic active colitis with cryptitis and crypt abscesses along with glandular distortion (G, H).