1485 Randomized clinical trial of infliximab versus vedolizumab for immune checkpoint inhibitor related colitis

<h3>Background</h3> Immune-mediated diarrhea and colitis (IMDC) is an inflammatory consequence of immunotherapy. Current management strategies are adopted from inflammatory bowel disease practice and rely on selective immunosuppressive therapy (SIT) with infliximab or vedolizumab in more severe cases. However, evidence supporting SIT use is limited to retrospective studies.^1–3 Here we present the preliminary findings of 29 patients from the first clinical trial comparing the efficacy and safety of infliximab and vedolizumab in treating IMDC. <h3>Methods</h3> We conducted a randomized controlled trial of infliximab and vedolizumab in the treatment of IMDC in combination with steroid treatment. Patients included must have received immunotherapy and developed IMDC at CTCAE grade ≥2. Infusions were given around weeks 0, 2, and 6, and disease activity and adverse events were recorded over 12 weeks. Response and remission was reported at different timepoints. Fecal transplantation or ustekinumab would be considered for refractory cases after two SIT doses. <h3>Results</h3> 29 patients have been enrolled thus far, four were removed due to treatment failure and one withdrew consent at 2 months. Twelve patients were randomized to each arm respectively. At two weeks, clinical remission rates are similarly high across infliximab (91.7%) and vedolizumab (91.7%) groups. Symptom improvement was typically seen in a median of 2.5 days (IQR: 1.2–4.5) across both groups. Ten patients (83.3%) in either arm had achieved 30 days steroid-free remission. Symptom recurrence occurred in 1 patient in each arm by 12 weeks, and 2 patients in infliximab arm by 6 months. Three patients from either group were able to resume immunotherapy. Otherwise, both groups had a similar rate of mild adverse events (AEs), most of which were deemed unrelated to SIT use. <h3>Conclusions</h3> 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 having recurrent disease. The two drugs have a comparable safety profile with only mild AEs. Our preliminary findings suggest that both drugs can be used effectively in first-line treatment of IMDC in combination with shorter steroid course, but further data is necessary to ascertain long-term outcomes. <h3>Trial Registration</h3> NCT04407247. <h3>References</h3> Hamzah Abu-Sbeih, Faisal Ali, Zimu Gong, Wenyi Luo, Yinghong Wang. Outcomes of vedolizumab treatment in patients with immune checkpoint inhibitor induced diarrhea and colitis: a multi-center study. <i>Journal For Immunotherapy of Cancer</i> 2018 Dec 5;<b>6</b>(1):142, PMID: 30518410. Hamzah Abu-Sbeih, Faisal S Ali, Xuemei Wang, Niharika Mallepally, Ellie Chen, Mehmet Altan, Robert S Bresalier, Ramona Dadu, Amir Jazaeri, Bret Lashner, Yinghong Wang. Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor–induced colitis. <i>J Immunother Cancer</i>. 2019 Apr 2;<b>7</b>(1):93. doi: 10.1186/s40425-019-0577-1. PMID: 30940209. Fangwen Zou, David Faleck, Anusha Thomas, Jessica Harris, Deepika Satish, Xuemei Wang, Aline Charabaty, Marc S Ernstoff, Isabella C Glitza Oliva, Stephen Hanauer, Jennifer McQuade, Michel Obeid, Amishi Shah, David M Richards, Elad Sharon, Jedd Wolchok, John Thompson, Yinghong Wang. Efficacy and safety of vedolizumab and infliximab treatment for immune-mediated diarrhea and colitis in patients with cancer: a two-center observational study. <i>J Immunother Cancer</i>. 2021 Nov;<b>9</b>(11):e003277. doi: 10.1136/jitc-2021-003277. PMID: 34789551. <h3>Ethics Approval</h3> The University of Texas MD Anderson Cancer Center institutional research board 2019-0276. Participants gave informed consent before taking part of the study. <h3>Consent</h3> Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.