Predictors of Steroid Failure and Outcomes of Rescue Therapy in Severe ICI-Induced Colitis: A Multicenter Study from GETECCU.

Abstract

INTRODUCTION Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are frequently associated with immune-mediated colitis (IMC), a potentially severe complication. However, evidence on treatment effectiveness and predictors of response is limited. MATERIALS AND METHODS We conducted a multicenter, retrospective study promoted by GETECCU including adult patients with solid tumors who developed grade 3-4 IMC requiring hospitalization between 2014 and 2024. All patients received intravenous corticosteroids; those refractory to steroids could receive targeted therapies. Clinical symptoms were assessed using a modified partial Mayo score including abdominal pain, and endoscopic activity was evaluated with the UCEIS index. Treatment failure was defined as the need for rescue therapy, surgery, or death. RESULTS We included 211 patients (40% women, mean age 62 years). Corticosteroid response was achieved in 50.2% of cases. Non-responders had shorter time to IMC onset, prior outpatient steroid use, higher symptom severity, and more frequent moderate-to-severe endoscopic findings. Independent predictors of corticosteroid failure were prior oral corticosteroid use (OR 4.4), higher UCEIS score (OR 1.31), and higher modified Mayo score (OR 1.45). A total of 113 rescue therapies were administered, primarily infliximab, vedolizumab, or ustekinumab, with overall effectiveness rates of 65-72%. Clinical severity was the only factor associated with reduced response to rescue therapy. CONCLUSION Corticosteroid efficacy in severe IMC is limited. Clinical symptom severity and endoscopic ulcerations predict poor response to corticosteroids, while symptom severity also influences outcomes of biologic rescue therapy. Early identification of high-risk patients may improve treatment strategies.