Abstract

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

Nat Rev Gastroenterol Hepatol. 2023 Oct 3. doi: 10.1038/s41575-023-00838-4.Online ahead of print.

 

Holm H Uhlig 1 2 3Claire Booth 4 5Judy Cho 6Marla Dubinsky 7Anne M Griffiths 8 9Bodo Grimbacher 10 11 12Sophie Hambleton 13Ying Huang 14Kelsey Jones 15 16Jochen Kammermeier 17Hirokazu Kanegane 18Sibylle Koletzko 19 20Daniel Kotlarz 19 21 22Christoph Klein 19 21Michael J Lenardo 23Bernice Lo 24 25Dermot P B McGovern 26Ahmet Özen 27Lissy de Ridder 28Frank Ruemmele 29Dror S Shouval 30 31Scott B Snapper 32 33Simon P Travis 34 35 16Dan Turner 36David C Wilson 37 38Aleixo M Muise 8 9 39 40 41

 
     

Author information

1Translational Gastroenterology Unit, University of Oxford, Oxford, UK. holm.uhlig@ndm.ox.ac.uk.

2Department of Paediatrics, University of Oxford, Oxford, UK. holm.uhlig@ndm.ox.ac.uk.

3Biomedical Research Centre, University of Oxford, Oxford, UK. holm.uhlig@ndm.ox.ac.uk.

4UCL Great Ormond Street Institute of Child Health, London, UK.

5Department of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

6Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

7Department of Paediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

8SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, Toronto, Canada.

9Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, University of Toronto, Toronto, Canada.

10Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany.

11Department of Rheumatology and Clinical Immunology, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany.

12Institute of Immunology and Transplantation, Royal Free Hospital, University College London, London, UK.

13Primary Immunodeficiency Group, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK.

14Department of Gastroenterology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.

15Paediatric Gastroenterology, Great Ormond Street Hospital, London, UK.

16Kennedy Institute, University of Oxford, Oxford, UK.

17Gastroenterology Department, Evelina London Children's Hospital, London, UK.

18Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

19Dr. von Hauner Children's Hospital, Department of Paediatrics, University Hospital, LMU Munich, Munich, Germany.

20Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.

21German Center for Child and Adolescent Health, Munich, Germany.

22Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

23Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

24Research Branch, Sidra Medicine, Doha, Qatar.

25College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.

26F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

27Marmara University Division of Allergy and Immunology, Istanbul, Turkey.

28Department of Paediatric Gastroenterology, Erasmus University Medical Center Sophia Children's Hospital, Rotterdam, Netherlands.

29Université Paris Cité, APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France.

30Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

31Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

32Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA, USA.

33Department of Paediatrics and Department of Medicine, Harvard Medical School, Boston, MA, USA.

34Translational Gastroenterology Unit, University of Oxford, Oxford, UK.

35Biomedical Research Centre, University of Oxford, Oxford, UK.

36Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

37Child Life and Health, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.

38Department of Paediatric Gastroenterology, The Royal Hospital for Children, and Young People, Edinburgh, UK.

39Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.

40Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.

41Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

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.

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