Exposure–response of ciclosporin and methotrexate in children and young people with severe atopic dermatitis: a secondary analysis of the TREatment of severe Atopic dermatitis Trial (TREAT)
This is a secondary analysis of a multicentre randomized controlled trial of ciclosporin and methotrexate in children and young people (CYP) with severe atopic dermatitis (AD). Longitudinal trough ciclosporin and erythrocyte methotrexate polyglutamate (MTX-PG) concentrations were measured to evaluate their associations with treatment response and adverse events. Both ciclosporin (4 mg kg-1 daily) and methotrexate (0.4 mg kg-1 weekly) led to a significant reduction in disease severity scores over the 36-week treatment period. Higher trough ciclosporin concentrations were associated with lower disease severity scores and may serve as a useful tool for therapeutic drug monitoring of ciclosporin in CYP with AD. However, in contrast to a previously published study, steady-state erythrocyte-MTX-PG concentrations showed no significant association with treatment response. Drug concentrations were comparable between patients with and without drug-related adverse events.
Authors
- Tess McPherson (ORCID: https://orcid.org/0000-0001-9215-0302)
- Ashley P Jones (ORCID: https://orcid.org/0000-0001-5253-730X)
- Anna Rosala‐Hallas (ORCID: https://orcid.org/0000-0001-8012-9995)
- Catherine Spowart (ORCID: https://orcid.org/0000-0001-8641-2871)
- Mandy Wan (ORCID: https://orcid.org/0000-0001-8802-0425)
- Manish D. Sinha (ORCID: https://orcid.org/0000-0001-7593-1203)
- Monica Arenas-Hernandez
- Ben Esdaile
- Donal O’Kane (ORCID: https://orcid.org/0000-0003-0190-6114)
- Michael J. Cork (ORCID: https://orcid.org/0000-0003-4428-2428)
- Farhiya Ashoor
- Marie‐Louise Lovgren (ORCID: https://orcid.org/0000-0002-1220-716X)
- Lindsay Shaw (ORCID: https://orcid.org/0000-0002-2778-9035)
- Tracey Sach (ORCID: https://orcid.org/0000-0002-8098-9220)
- Carsten Flohr (ORCID: https://orcid.org/0000-0003-4884-6286)
- Danielle Greenblatt (ORCID: https://orcid.org/0000-0002-7505-3567)
- Fiona Browne (ORCID: https://orcid.org/0000-0002-0194-480X)
- J. E. Gach (ORCID: https://orcid.org/0000-0002-0333-7165)
- Emma Howard (ORCID: https://orcid.org/0000-0001-8411-5734)
- Susannah Baron (ORCID: https://orcid.org/0000-0003-2639-7854)
- Daniel K. Maskrey (ORCID: https://orcid.org/0000-0002-1514-1565)
- Paula Ruth Williamson (ORCID: https://orcid.org/0000-0001-9802-6636)
- Eva Hilger
- Alan D. Irvine (ORCID: https://orcid.org/0000-0002-9048-2044)
- Bjorn Thomas (ORCID: https://orcid.org/0000-0002-1815-3502)
- Jane Ravenscroft (ORCID: https://orcid.org/0000-0002-1609-7084)
- Sara Jo Brown (ORCID: https://orcid.org/0000-0002-3232-5251)
- Paula Beattie (ORCID: https://orcid.org/0009-0009-5205-0572)
- Ross Hearn
- Suzannah August
Institutions
- Belfast Health and Social Care Trust (GB)
- Nottingham University Hospitals NHS Trust (GB)
- University of Liverpool (GB)
- Queen Mary University of London (GB)
- King's College London (GB)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- Trinity College Dublin (IE)
- Royal Hospital for Children (GB)
- Poole Hospital (GB)
- Bristol Royal Hospital for Children (GB)
- Ninewells Hospital (GB)
- Whittington Hospital (GB)
- University Hospitals Coventry and Warwickshire NHS Trust (GB)
- Children's Health Ireland at Crumlin (IE)
- Birmingham Children's Hospital (GB)
- Thomas Foundation (AU)
- Sheffield Children's NHS Foundation Trust (GB)
- Whittington Health NHS Trust (GB)
- Evelina London Children's Healthcare (GB)
- Oxford University Hospitals NHS Trust (GB)
- Birmingham Women’s and Children’s NHS Foundation Trust (GB)
- University of Southampton (GB)
- University Hospitals Dorset NHS Foundation Trust
- University College London (GB)
- University of Sheffield (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Clinical and Experimental Dermatology
- Published
- 2025-03-30
- DOI
- https://doi.org/10.1093/ced/llaf147
- Primary Topic
- Dermatology and Skin Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00