TY - JOUR
T1 - Pharmacological Interventions for the Prevention and Treatment of Immune Checkpoint Inhibitor-Associated Enterocolitis
T2 - A Systematic Review
AU - Ma, Christopher
AU - MacDonald, John K.
AU - Nguyen, Tran M.
AU - Vande Casteele, Niels
AU - Linggi, Bryan
AU - Lefevre, Pavine
AU - Wang, Yinghong
AU - Feagan, Brian G.
AU - Jairath, Vipul
N1 - Funding Information:
CM has received consulting fees from AbbVie, AVIR Pharma Inc, Janssen, Takeda, Pfizer, Roche, Alimentiv (formerly Robarts Clinical Trials Inc); speaker's fees from AbbVie, Janssen, Takeda, and Pfizer; research support from the Canadian IBD Research Consortium, Ferring, and Pfizer. JKM is an employee of Alimentiv, Inc. TMN is an employee of Alimentiv, Inc. NVC has received research and consulting support from Takeda and UCB, research support from R-Biopharm and consulting support from Janssen, Pfizer, Progenity and Prometheus. BL is an employee of Alimentiv, Inc. PL is an employee of Alimentiv, Inc. YW has received consulting fees from Tillotts Pharma. BGF has received grant/research support from AbbVie Inc, Amgen Inc, AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals Ltd., Boehringer‐Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann‐La Roche Ltd., Gilead Sciences Inc, GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc, Receptos Inc/Celgene International, Sanofi, Santarus Inc, Takeda Development Center Americas Inc, Tillotts Pharma AG, and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc, Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc, Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., and Zyngenia; speakers bureau fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc, Boehringer‐Ingelheim, Bristol‐Myers Squibb, Celgene, Centocor Inc, Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; and is the Senior Scientific Officer of Alimentiv (formerly Robarts Clinical Trials Inc). VJ has received consulting fees from AbbVie, Takeda, Eli Lilly, Pfizer, Janssen, Ferring, Shire, Merck, GSK, Celltrion and Alimentiv (formerly Robarts Clinical Trials Inc); serves as an advisory board member for AbbVie, Takeda, Janssen, Arena, GSK, Eli Lilly and Ferring; has received speakers' bureau fees from Takeda, AbbVie, Janssen, Pfizer, Shire and Ferring.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/4
Y1 - 2022/4
N2 - Background: Patients treated with immune checkpoint inhibitors (ICIs) may develop ICI-associated enterocolitis, for which there is no approved treatment. Aims: We aimed to systematically review the efficacy and safety of medical interventions for the prevention and treatment of ICI-associated enterocolitis. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs), cohort and case–control studies, and case series/reports, evaluating interventions (including corticosteroids, biologics, aminosalicylates, immunosuppressants, and fecal transplantation) for ICI-associated enterocolitis. Clinical, endoscopic, and histologic efficacy endpoints were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to assess overall quality of evidence. Results: A total of 160 studies (n = 1514) were included (one RCT, 3 retrospective cohort studies, 156 case reports/case series). Very low quality evidence from one RCT suggests budesonide is not effective for prevention of ICI-associated enterocolitis in ipilimumab-treated patients (relative risk 0.93 [95% confidence interval 0.56, 1.56]). Very low quality evidence suggests that corticosteroids, infliximab, and vedolizumab may be effective for treatment of ICI-associated enterocolitis by inducing clinical response and remission. No validated indices for measuring disease activity were used. Biologic treatment was used in 42% (641/1528) of patients, as reported in 97 studies. ICIs were discontinued in 65% (457/702) of patients, as reported in 63 studies. Conclusions: Current treatment recommendations for ICI-associated enterocolitis are based on very low quality evidence, primarily from case reports and case series. Large-scale prospective cohort studies and RCTs are needed to develop prophylactic and therapeutic treatments to minimize interruption or discontinuation of oncological therapies.
AB - Background: Patients treated with immune checkpoint inhibitors (ICIs) may develop ICI-associated enterocolitis, for which there is no approved treatment. Aims: We aimed to systematically review the efficacy and safety of medical interventions for the prevention and treatment of ICI-associated enterocolitis. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs), cohort and case–control studies, and case series/reports, evaluating interventions (including corticosteroids, biologics, aminosalicylates, immunosuppressants, and fecal transplantation) for ICI-associated enterocolitis. Clinical, endoscopic, and histologic efficacy endpoints were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to assess overall quality of evidence. Results: A total of 160 studies (n = 1514) were included (one RCT, 3 retrospective cohort studies, 156 case reports/case series). Very low quality evidence from one RCT suggests budesonide is not effective for prevention of ICI-associated enterocolitis in ipilimumab-treated patients (relative risk 0.93 [95% confidence interval 0.56, 1.56]). Very low quality evidence suggests that corticosteroids, infliximab, and vedolizumab may be effective for treatment of ICI-associated enterocolitis by inducing clinical response and remission. No validated indices for measuring disease activity were used. Biologic treatment was used in 42% (641/1528) of patients, as reported in 97 studies. ICIs were discontinued in 65% (457/702) of patients, as reported in 63 studies. Conclusions: Current treatment recommendations for ICI-associated enterocolitis are based on very low quality evidence, primarily from case reports and case series. Large-scale prospective cohort studies and RCTs are needed to develop prophylactic and therapeutic treatments to minimize interruption or discontinuation of oncological therapies.
KW - Checkpoint inhibitor
KW - Cytotoxic T lymphocyte-associated protein
KW - Enterocolitis
KW - Immunotherapy
KW - Programmed cell death receptor
UR - http://www.scopus.com/inward/record.url?scp=85103351279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103351279&partnerID=8YFLogxK
U2 - 10.1007/s10620-021-06948-w
DO - 10.1007/s10620-021-06948-w
M3 - Review article
C2 - 33770330
AN - SCOPUS:85103351279
SN - 0163-2116
VL - 67
SP - 1128
EP - 1155
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 4
ER -