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Inflammation across tissues: can shared cell biology help design smarter trials?

Nature Reviews Rheumatology volume 19, pages 666–674 (2023)Cite this article

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An Author Correction to this article was published on 26 October 2023

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Abstract

Immune-mediated inflammatory diseases (IMIDs) are responsible for substantial global disease burden and associated health-care costs. Traditional models of research and service delivery silo their management within organ-based medical disciplines. Very often patients with disease in one organ have comorbid involvement in another, suggesting shared pathogenic pathways. Moreover, different IMIDs are often treated with the same drugs (including glucocorticoids, immunoregulators and biologics). Unlocking the cellular basis of these diseases remains a major challenge, leading us to ask why, if these diseases have so much in common, they are not investigated in a common manner. A tissue-based, cellular understanding of inflammation might pave the way for cross-disease, cross-discipline basket trials (testing one drug across two or more diseases) to reduce the risk of failure of early-phase drug development in IMIDs. This new approach will enable rapid assessment of the efficacy of new therapeutic agents in cross-disease translational research in humans.

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Fig. 1: Organ-based and molecular taxonomies of immune-mediated inflammatory diseases.
Fig. 2: The current approach to trials of new therapies in immune-mediated inflammatory diseases.

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Acknowledgements

S.P.L.T., H.H.U. and C.D.B. are supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), University of Oxford. H.H.U. is supported by The Leona M. and Harry B. Helmsley Charitable Trust.

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Authors and Affiliations

  1. Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK

    Tom Hosack, Tom Thomas, Rahul Ravindran, Simon Piers Leigh Travis & Christopher Dominic Buckley

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

    Tom Hosack, Tom Thomas, Rahul Ravindran, Hans Holm Uhlig & Simon Piers Leigh Travis

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

    Hans Holm Uhlig, Simon Piers Leigh Travis & Christopher Dominic Buckley

  4. Department of Paediatrics, University of Oxford, Oxford, UK

    Hans Holm Uhlig

  5. Institute for Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    Christopher Dominic Buckley

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All authors contributed to researching data for the article, discussion of content, writing the article and reviewing and editing the manuscript before submission.

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Competing interests

T.T. has received grants and research support from Celsius Therapeutics, and consulting fees from AbbVie and ZuraBio, and has been an employee of Janssen. H.H.U. has received research support and/or consultancy fees from BMS, Eli Lilly, Janssen, Mestag, OMass and UCB Pharma. S.P.L.T. has received grants and/or research support from AbbVie, Buhlmann, Celgene, Celsius Therapeutics, ECCO, Helmsley Trust, IOIBD, Janssen, Lilly, Pfizer, Takeda, UCB, UKIERI, Vifor and the Norman Collisson Foundation, and consulting fees from Abacus, AbbVie, Actial, ai4gi, Alcimed, Allergan, Amgen, Apexian, Aptel, Arena, Asahi, Aspen, Astellas, Atlantic, AstraZeneca, Bioclinica, Biogen, Boehringer Ingelheim, BMS, Buhlmann, Calcico, Celgene, Cellerix, Cerimon, ChemoCentryx, CisBio, Clario, Coronado, Cosmo, Dynavax, Enterome, EQrX, Equillium, Falk, Ferring, Galapagos, Genentech/Roche, Genzyme, Gilead, GSK, Immunocore, Immunometabolism, Janssen, Lilly, Medarex, Merck, Mestag, Neovacs, Novartis, Novo Nordisk, Otsuka, Pentax, Pfizer, Phesi, Phillips, Protagonist, Proximagen, Resolute, Sandoz, Sanofi, Satisfai, Sorriso, Syndermix, Synthon, Takeda, Theravance, Tigenix, Tillotts, Topivert, TxCell, UCB Pharma, Vertex, VHsquared, Vifor, Warner Chilcott and Zeria, and speaker fees from AbbVie, Amgen, Biogen, BMS, Falk, Ferring, Janssen, Lilly, Pfizer, Shire, Takeda and UCB. No stocks or shares. C.D.B. has received research support and/or consultancy fees from Janssen, GSK, BMS, Celsius, Novartis and Roche, and has stocks or share options for Mestag. T.H. and R.R. declare no competing interests.

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Hosack, T., Thomas, T., Ravindran, R. et al. Inflammation across tissues: can shared cell biology help design smarter trials?. Nat Rev Rheumatol 19, 666–674 (2023). https://doi.org/10.1038/s41584-023-01007-2

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