Oral beclomethasone dipropionate is an effective treatment for immune checkpoint inhibitor induced colitis.

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 hypothesized 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 centers between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5 mg 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 (14 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 (common terminology criteria for adverse events, CTCAE grade diarrhea=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 diarrhea=0). Ten patients (45%) had symptomatic relapse on cessation of BD, half within 7 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 randomized studies are needed to confirm these findings and determine the optimum dosing regimen.
Competing Interests: Competing interests: JLA reports meeting travel support from Vifor Pharma. NP reports he has served as a speaker for Allergan, Bristol Myers Squibb, Falk, Ferring, Janssen, Pfizer, Tillotts, and Takeda, and as a consultant and/or an advisory board member for AbbVie, Allergan, Celgene, Bristol Myers Squibb, Ferring, and Vifor Pharma. JL reports institution grants from Achilles therapeutics, BMS, Merck Sorono, Nektar, Novartis, Pfizer, Roche, Immunocore, Aveo and Pharmacyclics, consulting fees from Iovance, Boston Biomedical, Pfizer, BMS, GSK, Novartis, Incyte, Immunocore, YKT Global, iOnctura and Apple Tree, honoraria from Roche, Novartis, iOnctura, BMS, Pfizer, Incyte, Dynavax, CRUK, GSK, Eisai, Merck, TouchIME and Touch Experts and support for meeting attendance and/or travel from BMS, iOnctura, Roche, Pfizer, Incyte, Merck, Novartis, Pierre Fabre, BUG, ESMO, AIM, AstraZeneca, NCRI, Syneos Health, EUSA, KCA, Bioevents, MedConcept, GSK and RVMais. ST reports grants or contracts from Cancer Research UK (grant reference number C50947/A18176), The National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), The Kidney and Melanoma Cancer Fund of the Royal Marsden Cancer Charity, The Rosetrees Trust (grant reference number A2204) and Ventana Medical Systems Inc (grant reference numbers 10467 and 10530), honoraria from Jules Bordet Institute, Erasmus, Open Health and MD Anderson, support for attending meetings and/or travel from Jules Bordet Institute, ESMO, SMR, Broad, KCA, IFOM, EORTC, ASCO, Ventana, Roche, Institute of Molecular medicine, KTH Sweden, Pfizer, Erasmus, Systems biology, MD Anderson, WK Weiser, AACR, Research degrees Team, Melanoma Focus and SITC, patents Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB.
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