Randomized clinical trial of infliximab versus vedolizumab for immune checkpoint inhibitor related colitis.
Authors: Wang Yinghong , Varatharajalu Krishnavathana , Shatila Malek , Junek Kristin , Ninoska Ninoska Nataly , Msaouel Pavlos , Campbell Matthew T , Amaria Rodabe Navroze , Thomas Anusha 
Published: June 2024

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Background: Immune-mediated diarrhea and colitis (IMDC) is an inflammatory consequence of immunotherapy that frequently necessitates discontinuation of immunotherapy. Current management strategies are adopted from inflammatory bowel disease practice and rely on selective immunosuppressive therapy (SIT) with infliximab or vedolizumab as first-line in more severe cases. While this practice is widely accepted, evidence supporting SIT use is limited to retrospective studies. Here we present the preliminary findings of 22 patients from the first clinical trial comparing the efficacy and safety of infliximab and vedolizumab in treating IMDC. Methods: We conducted a randomized controlled trial of infliximab and vedolizumab in the treatment of IMDC. To be included, patients must have received immunotherapy and developed immune-mediated diarrhea or colitis at CTCAE grade ≥2. Infusions were given around weeks 0, 2, and 6, and disease activity and incidence of adverse events were recorded over 12 weeks of follow-up. Remission was defined as symptom improvement to CTCAE grade ≤1 by week 2. Fecal transplantation or ustekinumab would be considered for patients who are refractory to two SIT doses. Results: 22 patients have been enrolled thus far, three of whom were removed from the study and one who withdrew consent at 2 months. Ten patients were randomized to the infliximab arm and nine to the vedolizumab arm. At two weeks, clinical remission rates are similarly high across infliximab (90%) and vedolizumab (88.9%) groups, with the one patient in the vedolizumab group having symptom improvement but failing to meet criteria for clinical remission and one in the infliximab group with treatment failure. Symptom improvement was typically seen in a median of 3 days (IQR: 1.5-5.5) across both groups. Eight patients (80%) in the infliximab group and seven patients (77.8%) in the vedolizumab group had steroid-free remission at one month. Four patients (40%) from the infliximab group and three (33.3%) from the vedolizumab group had symptom recurrence in a median of 43 days across both groups (IQR: 39-93). Three patients from either group were able to resume immunotherapy. In terms of safety, both groups had a similar rate of mild adverse events (AEs), most of which were deemed unrelated to SIT use. Conclusions: This is the first randomized controlled trial to evaluate the safety and efficacy of infliximab and vedolizumab in the management of IMDC. Our results suggest that both agents are equally effective at controlling symptoms within two weeks of the first infusion, with a small number of patients receiving either having recurrent disease. The two drugs have a comparable safety profile with primarily mild AEs occurring. Our preliminary findings suggest that both drugs can be used effectively in first-line treatment of IMDC, but further data is necessary to ascertain long-term outcomes. Clinical trial information: NCT04407247 .