Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors

Background Limited data exist for management strategies targeting immunotherapy-related enteritis (irEnteritis). Systemic corticosteroids are commonly used but often are limited by adverse events. Enteric corticosteroids such as budesonide offer an attractive alternative; however, the ileocolonic re...

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Main Authors: Amitabh Srivastava, Michael Postow, David Faleck, Patrick Tiongco Magahis, Tara Corso, Pamela Livingstone, Erika Tom
Format: Article
Language:English
Published: BMJ Publishing Group 2024-07-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/7/e009051.full
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author Amitabh Srivastava
Michael Postow
David Faleck
Patrick Tiongco Magahis
Tara Corso
Pamela Livingstone
Erika Tom
author_facet Amitabh Srivastava
Michael Postow
David Faleck
Patrick Tiongco Magahis
Tara Corso
Pamela Livingstone
Erika Tom
author_sort Amitabh Srivastava
collection DOAJ
description Background Limited data exist for management strategies targeting immunotherapy-related enteritis (irEnteritis). Systemic corticosteroids are commonly used but often are limited by adverse events. Enteric corticosteroids such as budesonide offer an attractive alternative; however, the ileocolonic release of enteric-coated budesonide has limited utility for diffuse enteritis. Open-capsule budesonide (OCB) is a novel therapeutic approach that offers drug delivery throughout the small bowel. We report outcomes in patients treated with OCB for confirmed or suspected irEnteritis.Methods This retrospective cohort included all individuals treated with OCB for irEnteritis at Memorial Sloan Kettering from July 2018 to August 2023. Primary outcomes included clinical response, clinical remission, and corticosteroid-free remission following OCB. Secondary outcomes were OCB-related adverse events and efficacy by gastrointestinal toxicity location.Results 19 patients (53% female) with irEnteritis were treated with OCB. All patients presented with diarrhea; 15 (79%) reported anorexia with median 6 kg weight loss. 17 patients (89%) underwent esophagogastroduodenoscopy with biopsies revealing enteritis in all; 8 (42%) had concomitant colitis. 15 (79%) patients were treated previously with systemic corticosteroids: 8 (53%) were corticosteroid-dependent while 7 (47%) demonstrated non-response. 18 patients (95%) achieved clinical response, 15 (79%) attained clinical remission, and 11 (58%) had corticosteroid-free remission. Response to OCB was rapid with improvement noted after a median 4 days. 14 (74%) patients restored their pre-irEnteritis weight by OCB cessation. One mild, self-resolving adverse event was reported.Conclusions OCB is a safe and effective therapy for irEnteritis. OCB avoids systemic immunosuppression and successfully achieves clinical response and remission even in patients previously nonresponsive to systemic corticosteroids. Future studies are needed to optimize indications and duration.
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spelling doaj-art-ed4d97b7e2d04749a60fd5d35c7d1c652025-08-20T03:00:04ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-07-0112710.1136/jitc-2024-009051Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitorsAmitabh Srivastava0Michael Postow1David Faleck2Patrick Tiongco Magahis3Tara Corso4Pamela Livingstone5Erika Tom6Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USAMemorial Sloan Kettering Cancer Center, New York, NY, USAWeill Cornell Medical College, New York, New York, USAWeill Cornell Medical College, New York, New York, USAGastroenterology, Hepatology, and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USAGastroenterology, Hepatology, and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USAGastroenterology, Hepatology, and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USABackground Limited data exist for management strategies targeting immunotherapy-related enteritis (irEnteritis). Systemic corticosteroids are commonly used but often are limited by adverse events. Enteric corticosteroids such as budesonide offer an attractive alternative; however, the ileocolonic release of enteric-coated budesonide has limited utility for diffuse enteritis. Open-capsule budesonide (OCB) is a novel therapeutic approach that offers drug delivery throughout the small bowel. We report outcomes in patients treated with OCB for confirmed or suspected irEnteritis.Methods This retrospective cohort included all individuals treated with OCB for irEnteritis at Memorial Sloan Kettering from July 2018 to August 2023. Primary outcomes included clinical response, clinical remission, and corticosteroid-free remission following OCB. Secondary outcomes were OCB-related adverse events and efficacy by gastrointestinal toxicity location.Results 19 patients (53% female) with irEnteritis were treated with OCB. All patients presented with diarrhea; 15 (79%) reported anorexia with median 6 kg weight loss. 17 patients (89%) underwent esophagogastroduodenoscopy with biopsies revealing enteritis in all; 8 (42%) had concomitant colitis. 15 (79%) patients were treated previously with systemic corticosteroids: 8 (53%) were corticosteroid-dependent while 7 (47%) demonstrated non-response. 18 patients (95%) achieved clinical response, 15 (79%) attained clinical remission, and 11 (58%) had corticosteroid-free remission. Response to OCB was rapid with improvement noted after a median 4 days. 14 (74%) patients restored their pre-irEnteritis weight by OCB cessation. One mild, self-resolving adverse event was reported.Conclusions OCB is a safe and effective therapy for irEnteritis. OCB avoids systemic immunosuppression and successfully achieves clinical response and remission even in patients previously nonresponsive to systemic corticosteroids. Future studies are needed to optimize indications and duration.https://jitc.bmj.com/content/12/7/e009051.full
spellingShingle Amitabh Srivastava
Michael Postow
David Faleck
Patrick Tiongco Magahis
Tara Corso
Pamela Livingstone
Erika Tom
Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
Journal for ImmunoTherapy of Cancer
title Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
title_full Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
title_fullStr Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
title_full_unstemmed Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
title_short Open-capsule budesonide for the treatment of immune-related enteritis from checkpoint inhibitors
title_sort open capsule budesonide for the treatment of immune related enteritis from checkpoint inhibitors
url https://jitc.bmj.com/content/12/7/e009051.full
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