Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards

Holm H. Uhlig; Claire Booth; Judy Cho; Marla Dubinsky; Anne M. Griffiths; Bodo Grimbacher; Sophie Hambleton; Ying Huang; Kelsey Jones; Jochen Kammermeier; Hirokazu Kanegane; Sibylle Koletzko; Daniel Kotlarz; Christoph Klein; Michael J. Lenardo; Bernice Lo; Dermot P.B. McGovern; Ahmet Özen; Lissy de Ridder; Frank Ruemmele; Dror S. Shouval; Scott B. Snapper; Simon P. Travis; Dan Turner; David C. Wilson; Aleixo M. Muise

doi:10.1038/s41575-023-00838-4

Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards

Holm H. Uhlig^*, Claire Booth, Judy Cho, Marla Dubinsky, Anne M. Griffiths, Bodo Grimbacher, Sophie Hambleton, Ying Huang, Kelsey Jones, Jochen Kammermeier, Hirokazu Kanegane, Sibylle Koletzko, Daniel Kotlarz, Christoph Klein, Michael J. Lenardo, Bernice Lo, Dermot P.B. McGovern, Ahmet Özen, Lissy de Ridder, Frank RuemmeleDror S. Shouval, Scott B. Snapper, Simon P. Travis, Dan Turner, David C. Wilson, Aleixo M. Muise

^*Corresponding author for this work

Pediatrics

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

9 Scopus citations

Abstract

Owing to advances in genomics that enable differentiation of molecular aetiologies, patients with monogenic inflammatory bowel disease (mIBD) potentially have access to genotype-guided precision medicine. In this Expert Recommendation, we review the therapeutic research landscape of mIBD, the reported response to therapies, the medication-related risks and systematic bias in reporting. The mIBD field is characterized by the absence of randomized controlled trials and is dominated by retrospective observational data based on case series and case reports. More than 25 off-label therapeutics (including small-molecule inhibitors and biologics) as well as cellular therapies (including haematopoietic stem cell transplantation and gene therapy) have been reported. Heterogeneous reporting of outcomes impedes the generation of robust therapeutic evidence as the basis for clinical decision making in mIBD. We discuss therapeutic goals in mIBD and recommend standardized reporting (mIBD REPORT (monogenic Inflammatory Bowel Disease Report Extended Phenotype and Outcome of Treatments) standards) to stratify patients according to a genetic diagnosis and phenotype, to assess treatment effects and to record safety signals. Implementation of these pragmatic standards should help clinicians to assess the therapy responses of individual patients in clinical practice and improve comparability between observational retrospective studies and controlled prospective trials, supporting future meta-analysis.

Original language	English
Pages (from-to)	810-828
Number of pages	19
Journal	Nature Reviews Gastroenterology and Hepatology
Volume	20
Issue number	12
DOIs	https://doi.org/10.1038/s41575-023-00838-4
State	Published - Dec 2023

Funding

Funders	Funder number
NIHR Oxford Biomedical Research Centre
Egan Family Foundation
Children’s Rare Disease Cohort Initiative
Crohn's in Childhood Research Association
Leona M. and Harry B. Helmsley Charitable Trust
Canada Research Chairs
Canadian Institutes of Health Research
University of Oxford
XLP Research Trust
NIHR Great Ormond Street Hospital Biomedical Research Centre	390874280
Japan Society for the Promotion of Science	22K07887
NIDDK NIH	RC2DK118640
National Institute of Diabetes and Digestive and Kidney Diseases	RC2DK122532
Bundesministerium für Bildung und Forschung	GAIN 01GM1910A

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Uhlig, H. H., Booth, C., Cho, J., Dubinsky, M., Griffiths, A. M., Grimbacher, B., Hambleton, S., Huang, Y., Jones, K., Kammermeier, J., Kanegane, H., Koletzko, S., Kotlarz, D., Klein, C., Lenardo, M. J., Lo, B., McGovern, D. P. B., Özen, A., de Ridder, L., ... Muise, A. M. (2023). Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards. Nature Reviews Gastroenterology and Hepatology, 20(12), 810-828. https://doi.org/10.1038/s41575-023-00838-4

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title = "Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards",

abstract = "Owing to advances in genomics that enable differentiation of molecular aetiologies, patients with monogenic inflammatory bowel disease (mIBD) potentially have access to genotype-guided precision medicine. In this Expert Recommendation, we review the therapeutic research landscape of mIBD, the reported response to therapies, the medication-related risks and systematic bias in reporting. The mIBD field is characterized by the absence of randomized controlled trials and is dominated by retrospective observational data based on case series and case reports. More than 25 off-label therapeutics (including small-molecule inhibitors and biologics) as well as cellular therapies (including haematopoietic stem cell transplantation and gene therapy) have been reported. Heterogeneous reporting of outcomes impedes the generation of robust therapeutic evidence as the basis for clinical decision making in mIBD. We discuss therapeutic goals in mIBD and recommend standardized reporting (mIBD REPORT (monogenic Inflammatory Bowel Disease Report Extended Phenotype and Outcome of Treatments) standards) to stratify patients according to a genetic diagnosis and phenotype, to assess treatment effects and to record safety signals. Implementation of these pragmatic standards should help clinicians to assess the therapy responses of individual patients in clinical practice and improve comparability between observational retrospective studies and controlled prospective trials, supporting future meta-analysis.",

author = "Uhlig, {Holm H.} and Claire Booth and Judy Cho and Marla Dubinsky and Griffiths, {Anne M.} and Bodo Grimbacher and Sophie Hambleton and Ying Huang and Kelsey Jones and Jochen Kammermeier and Hirokazu Kanegane and Sibylle Koletzko and Daniel Kotlarz and Christoph Klein and Lenardo, {Michael J.} and Bernice Lo and McGovern, {Dermot P.B.} and Ahmet {\"O}zen and {de Ridder}, Lissy and Frank Ruemmele and Shouval, {Dror S.} and Snapper, {Scott B.} and Travis, {Simon P.} and Dan Turner and Wilson, {David C.} and Muise, {Aleixo M.}",

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year = "2023",

month = dec,

doi = "10.1038/s41575-023-00838-4",

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Uhlig, HH, Booth, C, Cho, J, Dubinsky, M, Griffiths, AM, Grimbacher, B, Hambleton, S, Huang, Y, Jones, K, Kammermeier, J, Kanegane, H, Koletzko, S, Kotlarz, D, Klein, C, Lenardo, MJ, Lo, B, McGovern, DPB, Özen, A, de Ridder, L, Ruemmele, F, Shouval, DS, Snapper, SB, Travis, SP, Turner, D, Wilson, DC & Muise, AM 2023, 'Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards', Nature Reviews Gastroenterology and Hepatology, vol. 20, no. 12, pp. 810-828. https://doi.org/10.1038/s41575-023-00838-4

TY - JOUR

T1 - Precision medicine in monogenic inflammatory bowel disease

T2 - proposed mIBD REPORT standards

AU - Uhlig, Holm H.

AU - Booth, Claire

AU - Cho, Judy

AU - Dubinsky, Marla

AU - Griffiths, Anne M.

AU - Grimbacher, Bodo

AU - Hambleton, Sophie

AU - Huang, Ying

AU - Jones, Kelsey

AU - Kammermeier, Jochen

AU - Kanegane, Hirokazu

AU - Koletzko, Sibylle

AU - Kotlarz, Daniel

AU - Klein, Christoph

AU - Lenardo, Michael J.

AU - Lo, Bernice

AU - McGovern, Dermot P.B.

AU - Özen, Ahmet

AU - de Ridder, Lissy

AU - Ruemmele, Frank

AU - Shouval, Dror S.

AU - Snapper, Scott B.

AU - Travis, Simon P.

AU - Turner, Dan

AU - Wilson, David C.

AU - Muise, Aleixo M.

PY - 2023/12

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N2 - Owing to advances in genomics that enable differentiation of molecular aetiologies, patients with monogenic inflammatory bowel disease (mIBD) potentially have access to genotype-guided precision medicine. In this Expert Recommendation, we review the therapeutic research landscape of mIBD, the reported response to therapies, the medication-related risks and systematic bias in reporting. The mIBD field is characterized by the absence of randomized controlled trials and is dominated by retrospective observational data based on case series and case reports. More than 25 off-label therapeutics (including small-molecule inhibitors and biologics) as well as cellular therapies (including haematopoietic stem cell transplantation and gene therapy) have been reported. Heterogeneous reporting of outcomes impedes the generation of robust therapeutic evidence as the basis for clinical decision making in mIBD. We discuss therapeutic goals in mIBD and recommend standardized reporting (mIBD REPORT (monogenic Inflammatory Bowel Disease Report Extended Phenotype and Outcome of Treatments) standards) to stratify patients according to a genetic diagnosis and phenotype, to assess treatment effects and to record safety signals. Implementation of these pragmatic standards should help clinicians to assess the therapy responses of individual patients in clinical practice and improve comparability between observational retrospective studies and controlled prospective trials, supporting future meta-analysis.

AB - Owing to advances in genomics that enable differentiation of molecular aetiologies, patients with monogenic inflammatory bowel disease (mIBD) potentially have access to genotype-guided precision medicine. In this Expert Recommendation, we review the therapeutic research landscape of mIBD, the reported response to therapies, the medication-related risks and systematic bias in reporting. The mIBD field is characterized by the absence of randomized controlled trials and is dominated by retrospective observational data based on case series and case reports. More than 25 off-label therapeutics (including small-molecule inhibitors and biologics) as well as cellular therapies (including haematopoietic stem cell transplantation and gene therapy) have been reported. Heterogeneous reporting of outcomes impedes the generation of robust therapeutic evidence as the basis for clinical decision making in mIBD. We discuss therapeutic goals in mIBD and recommend standardized reporting (mIBD REPORT (monogenic Inflammatory Bowel Disease Report Extended Phenotype and Outcome of Treatments) standards) to stratify patients according to a genetic diagnosis and phenotype, to assess treatment effects and to record safety signals. Implementation of these pragmatic standards should help clinicians to assess the therapy responses of individual patients in clinical practice and improve comparability between observational retrospective studies and controlled prospective trials, supporting future meta-analysis.

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Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards

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