Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective

Author:

Ramessur Ravi12,Dand Nick2ORCID,Langan Sinéad M3,Saklatvala Jake2,Fritzsche Marie-Christine45,Holland Suzi6,Arents Bernd W M7,McAteer Helen8,Proctor Andrew9,McMahon David10,Greenwood Michelle10,Buyx Alena M45,Messer Tamara11,Weiler Nina11,Hicks Alexandra12,Hecht Peter13,Weidinger Stephan14,Ndlovu Matladi N15,Chengliang Dai16,Hübenthal Matthias17,Egeberg Alexander1819,Paternoster Lavinia2021,Skov Lone1922ORCID,De Jong Elke M G J23,Middelkamp-Hup Maritza A24,Mahil Satveer K12,Barker Jonathan N12,Flohr Carsten25ORCID,Brown Sara J2627,Smith Catherine H1ORCID

Affiliation:

1. St John’s Institute of Dermatology

2. Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London , London , UK

3. London School of Hygiene & Tropical Medicine , London , UK

4. Institute of History and Ethics in Medicine, TUM School of Medicine

5. Department of Science, Technology and Society, School of Social Sciences and Technology, Technical University of Munich , Munich , Germany

6. Eczema Outreach Support , Linlithgow , UK

7. Dutch Association for People with Atopic Dermatitis , Nijkerk , the Netherlands

8. The Psoriasis Association , Northampton , UK

9. National Eczema Society , London , UK

10. Irish Skin Foundation , Dublin , Ireland

11. EURICE – European Research and Project Office GmbH , St. Ingbert , Germany

12. Immunology & Inflammation Research Therapeutic Area , Sanofi, Cambridge, MA , USA

13. Public Private Partnerships, Sanofi Partnering , Frankfurt , Germany

14. Department of Dermatology, Venerology and Allergology, University Hospital Schleswig-Holstein , Kiel , Germany

15. UCB Pharma , Brussels , Belgium

16. Translational Medicine Department , UCB S.A., London , UK

17. Department of Dermatology, Quincke Research Center, University Hospital Schleswig-Holstein , Campus Kiel, Kiel , Germany

18. Department of Dermatology, Bispebjerg Hospital , Copenhagen , Denmark

19. Department of Clinical Medicine, University of Copenhagen , Copenhagen , Denmark

20. MRC Integrative Epidemiology Unit at the University of Bristol , Bristol , UK

21. Population Health Sciences, Bristol Medical School , Bristol, Bristol , UK

22. Department of Dermatology and Allergy, Copenhagen University Hospital – Herlev and Gentofte , Copenhagen , Denmark

23. Department of Dermatology, Radboud University Medical Centre , Nijmegen , the Netherlands

24. Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Amsterdam UMC, Academic Medical Center, University of Amsterdam , Amsterdam , the Netherlands

25. Unit for Paediatric and Population-Based Dermatology Research, St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London , London , UK

26. Centre for Genomic and Experimental Medicine, University of Edinburgh , Edinburgh , UK

27. Department of Dermatology , NHS Lothian, Edinburgh , UK

Abstract

Abstract More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.

Funder

Innovative Medicines Initiative 2 Joint Undertaking

European Union’s Horizon

European Federation of Pharmaceutical Industries and Associations

Health Data Research UK

National Institute for Health and Care Research

Wellcome Trust

Publisher

Oxford University Press (OUP)

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