Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?

Vincent Ting Fung Cheung; Tarun Gupta; Anna Olsson-Brown; Sreedhar Subramanian; Sarah Christina Sasson; Jonathan Heseltine; Eve Fryer; Elena Collantes; Joseph J Sacco; Munir Pirmohamed; Alison Simmons; Paul Klenerman; Mark Tuthill; Andrew S Protheroe; Meenali Chitnis; Benjamin Peter Fairfax; Miranda Jane Payne; Mark Ross Middleton; Oliver Brain

doi:10.1038/s41416-020-0882-y

Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?

Vincent Ting Fung Cheung
, Tarun Gupta
, Anna Olsson-Brown
, Sreedhar Subramanian
, Sarah Christina Sasson
, Jonathan Heseltine
, Eve Fryer
, Elena Collantes
, Joseph J Sacco
, Munir Pirmohamed
, Alison Simmons
, Paul Klenerman
, Mark Tuthill
, Andrew S Protheroe
, Meenali Chitnis
, Benjamin Peter Fairfax
, Miranda Jane Payne
, Mark Ross Middleton
, Oliver Brain

Cork University Dental School and Hospital

University of Oxford
Royal Liverpool University Hospital NHS Trust
Clatterbridge Cancer Centre NHS Foundation Trust
University of Liverpool
Oxford University Hospitals NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes.

METHODS: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018. Demographics, clinical data, endoscopies (reanalysed using Mayo/Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores), histology (scored with Nancy Index) and treatment outcomes were analysed.

RESULTS: In all, 1074 patients were analysed. Twelve percent (134) developed irAE colitis. Median patient age was 66, 59% were male. CTCAE diarrhoea grade does not correlate with steroid/ infliximab use. G3/4 colitis patients are more likely to need infliximab (p < 0.0001) but colitis grade does not correlate with steroid duration. CRP, albumin and haemoglobin do not correlate with severity. The UCEIS (p = 0.008) and Mayo (p = 0.016) scores correlate with severity/infliximab requirement. Patients with higher Nancy indices (3/4) are more likely to require infliximab (p = 0.03).

CONCLUSIONS: CTCAE assessment does not accurately reflect colitis severity and our data do not support its use in isolation, as this may negatively impact timely management. Our data support utilising endoscopic scoring for patients with >grade 1 CTCAE disease, and demonstrate the potential prognostic utility of objective histologic scoring.

Original language	English
Pages (from-to)	207-215
Number of pages	9
Journal	British Journal of Cancer
Volume	123
Issue number	2
DOIs	https://doi.org/10.1038/s41416-020-0882-y
Publication status	Published - Jul 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Aged
Carcinoma, Non-Small-Cell Lung/complications
Colitis/chemically induced
Colonoscopy
Drug-Related Side Effects and Adverse Reactions
Female
Humans
Immune Checkpoint Inhibitors/administration & dosage
Infliximab/administration & dosage
Male
Melanoma/complications
Middle Aged
Prognosis
Severity of Illness Index
Treatment Outcome
Urothelium/drug effects

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10.1038/s41416-020-0882-y

Cite this

Cheung, V. T. F., Gupta, T., Olsson-Brown, A., Subramanian, S., Sasson, S. C., Heseltine, J., Fryer, E., Collantes, E., Sacco, J. J., Pirmohamed, M., Simmons, A., Klenerman, P., Tuthill, M., Protheroe, A. S., Chitnis, M., Fairfax, B. P., Payne, M. J., Middleton, M. R., & Brain, O. (2020). Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way? British Journal of Cancer, 123(2), 207-215. https://doi.org/10.1038/s41416-020-0882-y

@article{e43ccbf08bb249839159936e72aba485,

title = "Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?",

abstract = "BACKGROUND: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes.METHODS: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018. Demographics, clinical data, endoscopies (reanalysed using Mayo/Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores), histology (scored with Nancy Index) and treatment outcomes were analysed.RESULTS: In all, 1074 patients were analysed. Twelve percent (134) developed irAE colitis. Median patient age was 66, 59\% were male. CTCAE diarrhoea grade does not correlate with steroid/ infliximab use. G3/4 colitis patients are more likely to need infliximab (p < 0.0001) but colitis grade does not correlate with steroid duration. CRP, albumin and haemoglobin do not correlate with severity. The UCEIS (p = 0.008) and Mayo (p = 0.016) scores correlate with severity/infliximab requirement. Patients with higher Nancy indices (3/4) are more likely to require infliximab (p = 0.03).CONCLUSIONS: CTCAE assessment does not accurately reflect colitis severity and our data do not support its use in isolation, as this may negatively impact timely management. Our data support utilising endoscopic scoring for patients with >grade 1 CTCAE disease, and demonstrate the potential prognostic utility of objective histologic scoring.",

keywords = "Aged, Carcinoma, Non-Small-Cell Lung/complications, Colitis/chemically induced, Colonoscopy, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Immune Checkpoint Inhibitors/administration \& dosage, Infliximab/administration \& dosage, Male, Melanoma/complications, Middle Aged, Prognosis, Severity of Illness Index, Treatment Outcome, Urothelium/drug effects",

author = "Cheung, \{Vincent Ting Fung\} and Tarun Gupta and Anna Olsson-Brown and Sreedhar Subramanian and Sasson, \{Sarah Christina\} and Jonathan Heseltine and Eve Fryer and Elena Collantes and Sacco, \{Joseph J\} and Munir Pirmohamed and Alison Simmons and Paul Klenerman and Mark Tuthill and Protheroe, \{Andrew S\} and Meenali Chitnis and Fairfax, \{Benjamin Peter\} and Payne, \{Miranda Jane\} and Middleton, \{Mark Ross\} and Oliver Brain",

year = "2020",

month = jul,

doi = "10.1038/s41416-020-0882-y",

language = "English",

volume = "123",

pages = "207--215",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "2",

}

Cheung, VTF, Gupta, T, Olsson-Brown, A, Subramanian, S, Sasson, SC, Heseltine, J, Fryer, E, Collantes, E, Sacco, JJ, Pirmohamed, M, Simmons, A, Klenerman, P, Tuthill, M, Protheroe, AS, Chitnis, M, Fairfax, BP, Payne, MJ, Middleton, MR & Brain, O 2020, 'Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?', British Journal of Cancer, vol. 123, no. 2, pp. 207-215. https://doi.org/10.1038/s41416-020-0882-y

TY - JOUR

T1 - Immune checkpoint inhibitor-related colitis assessment and prognosis

T2 - can IBD scoring point the way?

AU - Cheung, Vincent Ting Fung

AU - Gupta, Tarun

AU - Olsson-Brown, Anna

AU - Subramanian, Sreedhar

AU - Sasson, Sarah Christina

AU - Heseltine, Jonathan

AU - Fryer, Eve

AU - Collantes, Elena

AU - Sacco, Joseph J

AU - Pirmohamed, Munir

AU - Simmons, Alison

AU - Klenerman, Paul

AU - Tuthill, Mark

AU - Protheroe, Andrew S

AU - Chitnis, Meenali

AU - Fairfax, Benjamin Peter

AU - Payne, Miranda Jane

AU - Middleton, Mark Ross

AU - Brain, Oliver

PY - 2020/7

Y1 - 2020/7

N2 - BACKGROUND: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes.METHODS: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018. Demographics, clinical data, endoscopies (reanalysed using Mayo/Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores), histology (scored with Nancy Index) and treatment outcomes were analysed.RESULTS: In all, 1074 patients were analysed. Twelve percent (134) developed irAE colitis. Median patient age was 66, 59% were male. CTCAE diarrhoea grade does not correlate with steroid/ infliximab use. G3/4 colitis patients are more likely to need infliximab (p < 0.0001) but colitis grade does not correlate with steroid duration. CRP, albumin and haemoglobin do not correlate with severity. The UCEIS (p = 0.008) and Mayo (p = 0.016) scores correlate with severity/infliximab requirement. Patients with higher Nancy indices (3/4) are more likely to require infliximab (p = 0.03).CONCLUSIONS: CTCAE assessment does not accurately reflect colitis severity and our data do not support its use in isolation, as this may negatively impact timely management. Our data support utilising endoscopic scoring for patients with >grade 1 CTCAE disease, and demonstrate the potential prognostic utility of objective histologic scoring.

AB - BACKGROUND: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes.METHODS: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018. Demographics, clinical data, endoscopies (reanalysed using Mayo/Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores), histology (scored with Nancy Index) and treatment outcomes were analysed.RESULTS: In all, 1074 patients were analysed. Twelve percent (134) developed irAE colitis. Median patient age was 66, 59% were male. CTCAE diarrhoea grade does not correlate with steroid/ infliximab use. G3/4 colitis patients are more likely to need infliximab (p < 0.0001) but colitis grade does not correlate with steroid duration. CRP, albumin and haemoglobin do not correlate with severity. The UCEIS (p = 0.008) and Mayo (p = 0.016) scores correlate with severity/infliximab requirement. Patients with higher Nancy indices (3/4) are more likely to require infliximab (p = 0.03).CONCLUSIONS: CTCAE assessment does not accurately reflect colitis severity and our data do not support its use in isolation, as this may negatively impact timely management. Our data support utilising endoscopic scoring for patients with >grade 1 CTCAE disease, and demonstrate the potential prognostic utility of objective histologic scoring.

KW - Aged

KW - Carcinoma, Non-Small-Cell Lung/complications

KW - Colitis/chemically induced

KW - Colonoscopy

KW - Drug-Related Side Effects and Adverse Reactions

KW - Female

KW - Humans

KW - Immune Checkpoint Inhibitors/administration & dosage

KW - Infliximab/administration & dosage

KW - Male

KW - Melanoma/complications

KW - Middle Aged

KW - Prognosis

KW - Severity of Illness Index

KW - Treatment Outcome

KW - Urothelium/drug effects

U2 - 10.1038/s41416-020-0882-y

DO - 10.1038/s41416-020-0882-y

M3 - Article

C2 - 32418993

SN - 0007-0920

VL - 123

SP - 207

EP - 215

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?

Abstract

UN SDGs

Keywords

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