Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study

Background and aims The risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD.Metho...

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Main Authors: Wei Wei, Pauline Funchain, Ravi Shah, Joseph Sleiman, Muhammad Salman Faisal, Jessica Philpott
Format: Article
Language:English
Published: BMJ Publishing Group 2021-06-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/9/6/e002567.full
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author Wei Wei
Pauline Funchain
Ravi Shah
Joseph Sleiman
Muhammad Salman Faisal
Jessica Philpott
author_facet Wei Wei
Pauline Funchain
Ravi Shah
Joseph Sleiman
Muhammad Salman Faisal
Jessica Philpott
author_sort Wei Wei
collection DOAJ
description Background and aims The risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD.Methods Patients with IBD from a tertiary center cancer registry who underwent immune checkpoint inhibitor (ICI) therapy from 2011 to 2019 were identified. A 1:5 matched cohort of patients with and without a history of IBD was created, based on age, ICI therapy, and cancer type. Demographic data, clinical history of IBD, cancer, ICI agent, imDC events after ICI therapy, and overall survival were analyzed. Overall survival and time-to-imDC (TTimDC) were estimated by Kaplan-Meier and multivariate Cox proportional-hazards models.Results From a retrospective cohort of 3900 patients who received ICI therapy, 30 patients with IBD were matched with 150 patients without a history of IBD. Most patients received PD-1/PD-L1 inhibitor monotherapy (154/180, 85.6%). Individuals with preexisting IBD showed significantly shorter TTimDC than those in the non-IBD group (1-year imDC-free rate 67% vs 93%; HR 7.59, 95% CI 3.00 to 19.15, p<0.0001). Eleven (36%) from the IBD cohort experienced imDC events; none led to life-threatening conditions needing surgical interventions or death. Corticosteroids or biologics were needed in 8/11 (73%) patients, and discontinuation of therapy improved imDC in the remaining three. Half of patients required hospitalization. In contrast, no significant difference in overall survival was observed between IBD and non-IBD cohorts (HR 0.89, 95% CI 0.54 to 1.48). Both groups had overall comparable rates of other non-imDC immune-related adverse events.Conclusion Patients with preexisting IBD had worse time-to-imDC than non-IBD matched controls, yet did not exhibit worse overall survival. While close monitoring of patients with preexisting IBD is warranted while on immunotherapy, this comorbidity should not preclude ICI therapy if clinically required.
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spelling doaj-art-2bda733f61a847ab91079532f538fb5b2025-08-20T02:14:27ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-06-019610.1136/jitc-2021-002567Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective studyWei Wei0Pauline Funchain1Ravi Shah2Joseph Sleiman3Muhammad Salman Faisal4Jessica Philpott51 Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, ChinaCleveland Clinic Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USAEndocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USADepartment of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USADigestive Diseases & Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USABackground and aims The risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD.Methods Patients with IBD from a tertiary center cancer registry who underwent immune checkpoint inhibitor (ICI) therapy from 2011 to 2019 were identified. A 1:5 matched cohort of patients with and without a history of IBD was created, based on age, ICI therapy, and cancer type. Demographic data, clinical history of IBD, cancer, ICI agent, imDC events after ICI therapy, and overall survival were analyzed. Overall survival and time-to-imDC (TTimDC) were estimated by Kaplan-Meier and multivariate Cox proportional-hazards models.Results From a retrospective cohort of 3900 patients who received ICI therapy, 30 patients with IBD were matched with 150 patients without a history of IBD. Most patients received PD-1/PD-L1 inhibitor monotherapy (154/180, 85.6%). Individuals with preexisting IBD showed significantly shorter TTimDC than those in the non-IBD group (1-year imDC-free rate 67% vs 93%; HR 7.59, 95% CI 3.00 to 19.15, p<0.0001). Eleven (36%) from the IBD cohort experienced imDC events; none led to life-threatening conditions needing surgical interventions or death. Corticosteroids or biologics were needed in 8/11 (73%) patients, and discontinuation of therapy improved imDC in the remaining three. Half of patients required hospitalization. In contrast, no significant difference in overall survival was observed between IBD and non-IBD cohorts (HR 0.89, 95% CI 0.54 to 1.48). Both groups had overall comparable rates of other non-imDC immune-related adverse events.Conclusion Patients with preexisting IBD had worse time-to-imDC than non-IBD matched controls, yet did not exhibit worse overall survival. While close monitoring of patients with preexisting IBD is warranted while on immunotherapy, this comorbidity should not preclude ICI therapy if clinically required.https://jitc.bmj.com/content/9/6/e002567.full
spellingShingle Wei Wei
Pauline Funchain
Ravi Shah
Joseph Sleiman
Muhammad Salman Faisal
Jessica Philpott
Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
Journal for ImmunoTherapy of Cancer
title Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
title_full Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
title_fullStr Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
title_full_unstemmed Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
title_short Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study
title_sort incidence of immune checkpoint inhibitor mediated diarrhea and colitis imdc in patients with cancer and preexisting inflammatory bowel disease a propensity score matched retrospective study
url https://jitc.bmj.com/content/9/6/e002567.full
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