https://orcid.org/0000-0001-5436-1977
Lay Summary
Immune checkpoint inhibitor-induced (CPI) enterocolitis is a frequent complication of cancer immunotherapy. This case details the treatment of CPI enterocolitis with risankizumab (anti-IL23) and the use of intestinal ultrasound (IUS) to noninvasively monitor treatment response. This report is clinically relevant given the frequency of CPI enterocolitis and the expanding applications of IUS.
Introduction
Checkpoint inhibitor (CPI) enterocolitis is usually treated with prednisone, anti-TNF (infliximab), or anti-α4β7 (vedolizumab).1,2 Ustekinumab (anti-IL12/23) and fecal microbiota transplant have also been described.3,4 Here, we report risankizumab (anti-IL23) to treat and prevent recurrent CPI enterocolitis and demonstrate the utility of intestinal ultrasound (IUS) for diagnosing and monitoring CPI enterocolitis.
Case Report
A 47-year-old woman with psoriasis, quiescent on maintenance risankizumab, developed progression of metastatic melanoma while receiving pembrolizumab monotherapy (anti-PD-1). Her risankizumab was held and she received ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). After 3 cycles, and approximately 8 weeks after stopping risankizumab, she developed severe Grade 3 bloody diarrhea concerning for CPI enterocolitis. She had minimal response to prednisone 2 mg/kg daily. Sigmoidoscopy confirmed moderate proctosigmoiditis and biopsies revealed active colitis. IUS demonstrated increased bowel wall thickness (BWT) with hyperemia detected by color Doppler throughout most of the colon and terminal ileum, consistent with active inflammation (Figure 1A and B). Involvement in the ascending colon and terminal ileum was most prominent, with a Modified Limberg score of 3 for both segments and average BWT of 3.0 and 3.2 mm, respectively. The sigmoid colon also had an increased BWT of 3.3 mm with a Modified Limberg score of 2.
Intestinal ultrasound images of the sigmoid colon and terminal ileum before (A, B) and following (C, D) treatment with risankizumab. Pretreatment images show increased bowel wall thickness (BWT) >3.0 mm in both segments, with normalization of BWT post-treatment.
Given the diagnosis of CPI enterocolitis, she resumed risankizumab 150 mg subcutaneous (SC) injection. Her symptoms persisted, so her dose was escalated to Crohn’s disease induction dosing, 600 mg intravenous infusion, and her diarrhea resolved within 3 days. After 3 monthly infusions of risankizumab, her post-induction IUS showed normal BWT without hyperemia throughout, indicating complete sonographic resolution of enterocolitis (Figure 1C and D). She tapered off prednisone and resumed nivolumab with maintenance risankizumab 180 mg SC every 8 weeks without recurrence of colitis. Her risankizumab was temporarily held in the setting of pneumonia and bronchitis and later restarted after her pneumonia resolved.
Discussion
This case report demonstrates that risankizumab can effectively treat CPI enterocolitis, but higher dosing may be necessary to induce remission. Few reports describe using a maintenance biologic to safely resume immunotherapy in patients with CPI enterocolitis.5 Here, we report risankizumab as prophylaxis to prevent recurrent CPI enterocolitis when resuming immunotherapy.
IUS is an ideal noninvasive, point-of-care method for evaluating the extent of CPI enterocolitis and monitoring response to treatment. IUS is becoming the standard of care in inflammatory bowel disease, but there is only one other description of IUS for monitoring CPI enterocolitis.6 IUS does not require bowel preparation or fasting and noninvasively assesses ileal and colonic inflammation, making it ideal for monitoring CPI enterocolitis.
Acknowledgments
We acknowledge the patient, who consented to writing this case report.
Funding
None declared.
Conflicts of Interest
The Kattah lab receives research support from Eli Lilly. M.K. is a member of the scientific advisory boards of Santa Ana Bio and Switchback Therapeutics and has received consulting fees from Cellarity, Spyre Therapeutics, Morphic Therapeutic, Sonoma Biotherapeutics, and Surrozen. D.Y.O. has received research support from Merck, PACT Pharma, the Parker Institute for Cancer Immunotherapy, Poseida Therapeutics, TCR2 Therapeutics, Roche/Genentech, and Nutcracker Therapeutics; travel and accommodations from Roche/Genentech; and has consulted for Revelation Partners. K.K.T. reports institutional research support from ABM Therapeutics, AstraZeneca, BioAtla, Genentech, Ideaya Biosciences, Merck, OnKure, Pfizer, and Replimune; consulting honoraria from BMS.
