Oral Beclomethasone Dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis
File(s)
Published version
Author(s)
Alexander, James
Powell, Nick
Ibraheim, Hajir
Teare, Julian
Type
Journal Article
Abstract
Introduction
Systemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically-acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesised that BD would be an effective treatment for CPI-induced colitis.
Methods
We performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centres between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment.
Results
Twenty-two patients (fourteen male) with a median age of 64 (range 45-84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (CTCAE grade diarrhoea = 2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo endoscopic score [MES] = 2) in two patients (9%), mild inflammation (MES = 1) in nine patients (41%) and normal findings (MES = 0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhoea = 0). 10 patients (45%) had symptomatic relapse on cessation of BD, half within seven days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD.
Conclusions
Topical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflammation. In this study, BD was effective and safe at inducing remission in CPI-induced colitis, which was refractory to systemic corticosteroids. Further randomised studies are needed to confirm these findings and determine the optimum dosing regimen.
Systemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically-acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesised that BD would be an effective treatment for CPI-induced colitis.
Methods
We performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centres between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment.
Results
Twenty-two patients (fourteen male) with a median age of 64 (range 45-84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (CTCAE grade diarrhoea = 2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo endoscopic score [MES] = 2) in two patients (9%), mild inflammation (MES = 1) in nine patients (41%) and normal findings (MES = 0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhoea = 0). 10 patients (45%) had symptomatic relapse on cessation of BD, half within seven days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD.
Conclusions
Topical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflammation. In this study, BD was effective and safe at inducing remission in CPI-induced colitis, which was refractory to systemic corticosteroids. Further randomised studies are needed to confirm these findings and determine the optimum dosing regimen.
Date Issued
2022-09-16
Date Acceptance
2022-08-26
Citation
Journal for ImmunoTherapy of Cancer, 2022, 10 (9), pp.1-10
ISSN
2051-1426
Publisher
BMJ Publishing Group
Start Page
1
End Page
10
Journal / Book Title
Journal for ImmunoTherapy of Cancer
Volume
10
Issue
9
Copyright Statement
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See https://creativecommons.org/licenses/by/4.0/.
License URL
Sponsor
Freed Foundation
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://jitc.bmj.com/content/10/9/e005490
Grant Number
Freed Foundation
WT101159
RDA01
Subjects
Immunotherapy
Inflammation
Publication Status
Published
Date Publish Online
2022-09-16