Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis
Background Immune-related colitis is a common, often serious complication of immune checkpoint inhibition (ICI). Although endoscopy is not strictly recommended for any grade of diarrhea/colitis, emerging evidence suggests that endoscopic evaluation may have important therapeutic implications. In thi...
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000451.full |
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| author | Melissa Lumish Ryan J. Sullivan Douglas B. Johnson Michael Dougan Anita Giobbie-Hurder Meghan J Mooradian Daniel Y Wang Alexandra Coromilas Tianqi Chen |
| author_facet | Melissa Lumish Ryan J. Sullivan Douglas B. Johnson Michael Dougan Anita Giobbie-Hurder Meghan J Mooradian Daniel Y Wang Alexandra Coromilas Tianqi Chen |
| author_sort | Melissa Lumish |
| collection | DOAJ |
| description | Background Immune-related colitis is a common, often serious complication of immune checkpoint inhibition (ICI). Although endoscopy is not strictly recommended for any grade of diarrhea/colitis, emerging evidence suggests that endoscopic evaluation may have important therapeutic implications. In this retrospective study, we sought to comprehensively characterize the clinical and histologic features of ICI-induced colitis with a specific focus on evaluating the prognostic role of endoscopy.Methods Data were collected from the medical records of 130 patients with confirmed ICI-induced colitis. In a subset of patients (n=44) with endoscopic and pathologic data, endoscopic data were scored using the Mayo Endoscopic Score (MES) with scores ranging from 0 (no inflammation) to 3 (colonic ulceration). The impact of infliximab on antitumor outcomes was evaluated using progression-free survival (PFS) and overall survival (OS).Results We identified 130 patients with ICI-induced colitis across two institutions. All patients were treated with corticosteroids. Additional and/or alternative immunosuppression was employed in 59 cases, with 52 patients (42%) requiring at least one infusion of infliximab 5 mg/kg. Endoscopic assessment with biopsy was performed in 123 cases of suspected colitis (95%), with 44 cases available for MES tabulation. Presence of ulceration (MES 3) was associated with use of infliximab (p=0.008) and MES was significantly higher in patients who received infliximab compared with those who did not (p=0.003) with a median score of 2.5; conversely, those with an MES of zero rarely required secondary immunosuppression. Notably, symptoms of colitis based on Common Terminology Criteria for Adverse Events grade had no association with endoscopic findings based on MES classification. After adjustment for baseline patient and disease characteristics, there was no significant difference in steroid duration or cancer-related outcomes in patients treated with infliximab.Conclusions In our study, we demonstrate the association of endoscopic features, specifically the MES, with immunosuppressive needs. Importantly, we also show that MES was not related to severity of patient symptoms. The data suggest that endoscopic features can guide clinical decision-making better than patient symptoms, both identifying high-risk patients who will require infliximab and those who are likely to respond to initial corticosteroids. |
| format | Article |
| id | doaj-art-d3b12f2b32434816bb4e27679556ac4b |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d3b12f2b32434816bb4e27679556ac4b2025-08-20T02:49:50ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000451Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitisMelissa Lumish0Ryan J. Sullivan1Douglas B. Johnson2Michael Dougan3Anita Giobbie-Hurder4Meghan J Mooradian5Daniel Y Wang6Alexandra Coromilas7Tianqi Chen85 Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USAAff18 grid.32224.350000000403869924Massachusetts General Hospital Boston MA USA3 Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA1 Harvard Medical School, Boston, Massachusetts, USADivision of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA3 Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA3 Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA5 Department of Medicine, Columbia University, New York, New York, USA6 Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USABackground Immune-related colitis is a common, often serious complication of immune checkpoint inhibition (ICI). Although endoscopy is not strictly recommended for any grade of diarrhea/colitis, emerging evidence suggests that endoscopic evaluation may have important therapeutic implications. In this retrospective study, we sought to comprehensively characterize the clinical and histologic features of ICI-induced colitis with a specific focus on evaluating the prognostic role of endoscopy.Methods Data were collected from the medical records of 130 patients with confirmed ICI-induced colitis. In a subset of patients (n=44) with endoscopic and pathologic data, endoscopic data were scored using the Mayo Endoscopic Score (MES) with scores ranging from 0 (no inflammation) to 3 (colonic ulceration). The impact of infliximab on antitumor outcomes was evaluated using progression-free survival (PFS) and overall survival (OS).Results We identified 130 patients with ICI-induced colitis across two institutions. All patients were treated with corticosteroids. Additional and/or alternative immunosuppression was employed in 59 cases, with 52 patients (42%) requiring at least one infusion of infliximab 5 mg/kg. Endoscopic assessment with biopsy was performed in 123 cases of suspected colitis (95%), with 44 cases available for MES tabulation. Presence of ulceration (MES 3) was associated with use of infliximab (p=0.008) and MES was significantly higher in patients who received infliximab compared with those who did not (p=0.003) with a median score of 2.5; conversely, those with an MES of zero rarely required secondary immunosuppression. Notably, symptoms of colitis based on Common Terminology Criteria for Adverse Events grade had no association with endoscopic findings based on MES classification. After adjustment for baseline patient and disease characteristics, there was no significant difference in steroid duration or cancer-related outcomes in patients treated with infliximab.Conclusions In our study, we demonstrate the association of endoscopic features, specifically the MES, with immunosuppressive needs. Importantly, we also show that MES was not related to severity of patient symptoms. The data suggest that endoscopic features can guide clinical decision-making better than patient symptoms, both identifying high-risk patients who will require infliximab and those who are likely to respond to initial corticosteroids.https://jitc.bmj.com/content/8/1/e000451.full |
| spellingShingle | Melissa Lumish Ryan J. Sullivan Douglas B. Johnson Michael Dougan Anita Giobbie-Hurder Meghan J Mooradian Daniel Y Wang Alexandra Coromilas Tianqi Chen Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis Journal for ImmunoTherapy of Cancer |
| title | Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis |
| title_full | Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis |
| title_fullStr | Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis |
| title_full_unstemmed | Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis |
| title_short | Mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis |
| title_sort | mucosal inflammation predicts response to systemic steroids in immune checkpoint inhibitor colitis |
| url | https://jitc.bmj.com/content/8/1/e000451.full |
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