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

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)810-828
Number of pages19
JournalNature Reviews Gastroenterology and Hepatology
Volume20
Issue number12
DOIs
Publication statusPublished - 3 Oct 2023

Bibliographical note

Funding Information:
The authors thank patients and their families who have shared their experiences and contributed to research. The authors thank the Crohn’s in Childhood Research Association (CICRA), the XLP Research Trust and the Chronic Granulomatous Disorder Society (CGD Society) for their supportive feedback. A.M.M., H.H.U., C.K., D.K., S.B.S., J.C. and D.P.B.McG. are supported by the Leona M. and Harry B. Helmsley Charitable Trust. S.P.T. and H.H.U. are supported by the NIHR Oxford Biomedical Research Centre, University of Oxford; K.J. and C.B. are supported by the GOSH NIHR Biomedical Research Centre, London. B.G. is supported by RESIST-EXC 2155-Project (ID 390874280) and the BMBF (GAIN 01GM1910A). S.B.S is funded by the Wolpow Family Chair in IBD Treatment and Research, the Egan Family Foundation Chair, the Children’s Rare Disease Cohort Initiative, and NIDDK RC2DK122532. A.M.M. is funded by the Canada Research Chair (Tier 1) in Paediatric IBD, CIHR Foundation Grant, and NIDDK NIH (RC2DK118640 and RC2DK122532).

Publisher Copyright:
© 2023, Springer Nature Limited.

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