Ustekinumab for Refractory Colitis Associated with Immune Checkpoint Inhibitors

Abstract

Ustekinumab for Refractory Colitis Associated with Immune Checkpoint InhibitorsTo the Editor: Immune-mediated colitis, an adverse effect of therapy with immune checkpoint inhibitors that block the production of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1), 1 is managed with glucocorticoids, followed by the administration of infliximab or vedolizumab.Recently, tofacitinib was reported to be effective in one refractory case, although data are lacking with respect to evaluation and management. 2 Transplantation of fecal microbiota has shown favorable results in aggressive cases. 3 Here, we present two cases of refractory immune-mediated colitis that were managed with ustekinumab, a human monoclonal antibody against interleukin-12/23 that is routinely used in patients with severe Crohn's disease. 4 Patient 1, a 56-year-old man with stage III right axillary malignant melanoma, was treated with surgical resection, adjuvant radiation, and nivolumab.The treatment was complicated by the development of grade 3 diarrhea (according to the Common Terminology Criteria for Adverse Events), and nivolumab therapy was withheld.Colonoscopy in which biopsy specimens were obtained showed lymphocytic colitis.The patient had clinical remission of the diarrhea after three infusions of vedolizumab, but the colitis returned and did not respond to glucocorticoids or additional vedolizumab.After induction and three maintenance doses of ustekinumab, the patient had clinical remission from immune-mediated colitis and was cancer-free (Fig. 1A).Patient 2, a 61-year-old woman with stage IV left midback melanoma, underwent surgical excision and was treated with PD-1-directed nivolumab and radiation.Immunotherapy was withheld owing to the development of immune-mediated hepatitis.Consequent metastases to the lungs,

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