Introduction: Ustekinumab, a human monoclonal antibody to the interleukin (IL) 12/23 p40 subunit, is efficacious in the management of severe inflammatory bowel disease (IBD). Immune-mediated colitis (IMC) is a common immune checkpoint inhibitors (ICIs) toxicity that is similar to IBD. Robust data on optimal evidence-based management of IMC is lacking, and current medical therapy includes steroids, followed by infliximab (IFX) and/or vedolizumab (VDZ). Fecal microbiota transplantation (FMT) is used for colitis refractory to aforementioned therapies. To explore the efficacy of ustekinumab in managing refractory IMC, we present a case series of 19 patients who developed IMC and were treated with the same.
Methods: This is a retrospective chart review of cancer patients from two tertiary care centers who received ICI therapy and developed IMC refractory to standard of care treatments and were treated with ustekinumab. Clinical remission is defined as improvement in IMC grade to ≤ 1, and response as any improvement in GI symptoms.
Results: Of 19 patients in our cohort, the majority were Caucasians females with a median age of 63 years. The most common cancer type was melanoma (52.7%). Nine (47%) patients had received combination CTLA-4/PD-1 regimens prior to onset of IMC. Most (84.2%) patients had grade ≥3 diarrhea and 42.1% had ulcerative inflammation. All patients’ IMC remained clinically refractory to systemic steroids and IFX and/or VDZ, prompting initiation of ustekinumab. 13 (68.4%) improved following ustekinumab. Sixteen patients (84.2%) had clinical remission at last follow up. Eight patients in our cohort received FMT, 4 before and 4 after ustekinumab, six of whom improved after ustekinumab.
Discussion: IMC can be refractory to multiple lines of therapy including corticosteroids, IFX, VDZ, or FMT. IL12/23 inflammatory pathway may serve as a therapeutic target in managing such cases. The majority of patients in our case series had improvement in their IMC symptoms following ustekinumab, and only one patient experienced an adverse event. This result shows promise for the use of IL12/23 antagonists in the management of refractory IMC case, but further studies are still needed to validate its use.
