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

Journal: Nature reviews. Gastroenterology & hepatology 2024;20(12):810-828

PMID: 37789059

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.

© 2023. Springer Nature Limited.

Address: Translational Gastroenterology Unit, University of Oxford, Oxford, UK. [email protected].; Department of Paediatrics, University of Oxford, Oxford, UK. [email protected].; Biomedical Research Centre, University of Oxford, Oxford, UK. [email protected].; UCL Great Ormond Street Institute of Child Health, London, UK.; Department of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Paediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, Toronto, Canada.; Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, University of Toronto, Toronto, Canada.; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany.; Department of Rheumatology and Clinical Immunology, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany.; Institute of Immunology and Transplantation, Royal Free Hospital, University College London, London, UK.; Primary Immunodeficiency Group, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK.; Department of Gastroenterology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.; Paediatric Gastroenterology, Great Ormond Street Hospital, London, UK.; Kennedy Institute, University of Oxford, Oxford, UK.; Gastroenterology Department, Evelina London Children's Hospital, London, UK.; Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.; Dr. von Hauner Children's Hospital, Department of Paediatrics, University Hospital, LMU Munich, Munich, Germany.; Department of Paediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.; Dr. von Hauner Children's Hospital, Department of Paediatrics, University Hospital, LMU Munich, Munich, Germany.; German Center for Child and Adolescent Health, Munich, Germany.; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Dr. von Hauner Children's Hospital, Department of Paediatrics, University Hospital, LMU Munich, Munich, Germany.; German Center for Child and Adolescent Health, Munich, Germany.; Molecular 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.; Research Branch, Sidra Medicine, Doha, Qatar.; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.; F. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Marmara University Division of Allergy and Immunology, Istanbul, Turkey.; Department of Paediatric Gastroenterology, Erasmus University Medical Center Sophia Children's Hospital, Rotterdam, Netherlands.; Université Paris Cité, APHP, Hôpital Necker Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France.; Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, MA, USA.; Department of Paediatrics and Department of Medicine, Harvard Medical School, Boston, MA, USA.; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.; Biomedical Research Centre, University of Oxford, Oxford, UK.; Kennedy Institute, University of Oxford, Oxford, UK.; Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.; Child Life and Health, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.; Department of Paediatric Gastroenterology, The Royal Hospital for Children, and Young People, Edinburgh, UK.; SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, Toronto, Canada.; Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, University of Toronto, Toronto, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

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