Development of a Conceptual Disease Model of Atopic Dermatitis Using Data from the Phase 3 ARCADIA 1 Trial
7 affiliations
- 1George Washington University School of Medicine and Health Sciences, Washington, DC USA
- 2PPD Evidera Patient Centered Research, Thermo Fisher Scientific, Waltham, MA USA
- 3University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL USA
- 4San Diego School of Medicine, University of California, San Diego, CA USA
- 5SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON Canada
- 6Dermatology Centre, Northern Care Alliance NHS Foundation Trust and Division of Musculoskeletal and Dermatological Sciences, Manchester NIHR Biomedical Research Centre, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
- 7Galderma, Zählerweg 10, 6300 Zug, Switzerland
Abstract
Introduction: Patients with atopic dermatitis (AD) often experience severe skin disease, intense itching, sleep disturbance, and impaired quality of life (QoL). This study aimed to generate a clinically credible, data-driven conceptual disease model (CDM) of AD using baseline data from the phase 3 ARCADIA 1 trial of nemolizumab in patients with moderate-to-severe AD (NCT03985943).
Methods: Latent constructs were defined for skin severity, itch severity, sleep disturbance, and QoL/health status using validated clinical outcome assessments (COAs). Baseline COA data were obtained for the adult intent-to-treat population in ARCADIA 1. Structural equation modelling was conducted to assess direct and indirect relationships among AD domains. Factor loadings were calculated to evaluate COA-to-latent construct relationships, and regression coefficients were calculated to ensure that constructs had clinically interpretable directionality. To achieve consensus on the final model structure, model development and refinement were complemented by a modified Delphi process. Dermatologists with extensive experience managing moderate-to-severe AD and conducting AD clinical trials iteratively reviewed COA selection and latent construct definitions and proposed directional pathways.
Results: COA data from 807 adults with moderate-to-severe AD were used to generate the CDM. In the model, itch severity has a substantial impact on QoL, exerting both a direct effect (β = 0.427) and an indirect effect via sleep disturbance (itch severity → sleep disturbance: β = 0.702; sleep disturbance → QoL: β = 0.431). A significant bidirectional relationship between skin severity and itch severity is also observed (β = 0.367). COAs show strong loadings on their respective latent constructs.
Conclusions: The CDM identifies itch severity as a central driver of the patient burden in moderate-to-severe AD and supports prioritization of itch and sleep disturbance in clinical assessment, therapeutic planning, and outcome evaluation in AD. Our model, whose validity is strengthened by expert consensus, can potentially guide clinical decision-making and evaluation of treatment responses across key domains of AD burden.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s13555-026-01905-9.
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BibTeX
@article{silverberg2026development,
title = {{Development of a Conceptual Disease Model of Atopic Dermatitis Using Data from the Phase 3 ARCADIA 1 Trial}},
author = {Jonathan I. Silverberg and Patrick Daniele and Danielle Rodriguez and Sarah Mulnick and Gil Yosipovitch and Lawrence F. Eichenfield and Melinda Gooderham and Richard Warren and Ramkumar Subramanian and Katrin Jack and Liliana Ulianov and Christophe Piketty and Rajesh Rout and Jorge Puelles},
journal = {Dermatology and Therapy},
year = {2026},
month = sep,
doi = {10.1007/s13555-026-01905-9},
url = {https://doi.org/10.1007/s13555-026-01905-9},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Development of a Conceptual Disease Model of Atopic Dermatitis Using Data from the Phase 3 ARCADIA 1 Trial
AU - Jonathan I. Silverberg
AU - Patrick Daniele
AU - Danielle Rodriguez
AU - Sarah Mulnick
AU - Gil Yosipovitch
AU - Lawrence F. Eichenfield
AU - Melinda Gooderham
AU - Richard Warren
AU - Ramkumar Subramanian
AU - Katrin Jack
AU - Liliana Ulianov
AU - Christophe Piketty
AU - Rajesh Rout
AU - Jorge Puelles
PY - 2026
DA - 2026/09/01
JO - Dermatology and Therapy
DO - 10.1007/s13555-026-01905-9
UR - https://doi.org/10.1007/s13555-026-01905-9
AB - Introduction: Patients with atopic dermatitis (AD) often experience severe skin disease, intense itching, sleep disturbance, and impaired quality of life (QoL). This study aimed to generate a clinically credible, data-driven conceptual disease model (CDM) of AD using baseline data from the phase 3 ARCADIA 1 trial of nemolizumab in patients with moderate-to-severe AD (NCT03985943). Methods: Latent constructs were defined for skin severity, itch severity, sleep disturbance, and QoL/health status using validated clinical outcome assessments (COAs). Baseline COA data were obtained for the adult intent-to-treat population in ARCADIA 1. Structural equation modelling was conducted to assess direct and indirect relationships among AD domains. Factor loadings were calculated to evaluate COA-to-latent construct relationships, and regression coefficients were calculated to ensure that constructs had clinically interpretable directionality. To achieve consensus on the final model structure, model development and refinement were complemented by a modified Delphi process. Dermatologists with extensive experience managing moderate-to-severe AD and conducting AD clinical trials iteratively reviewed COA selection and latent construct definitions and proposed directional pathways. Results: COA data from 807 adults with moderate-to-severe AD were used to generate the CDM. In the model, itch severity has a substantial impact on QoL, exerting both a direct effect (β = 0.427) and an indirect effect via sleep disturbance (itch severity → sleep disturbance: β = 0.702; sleep disturbance → QoL: β = 0.431). A significant bidirectional relationship between skin severity and itch severity is also observed (β = 0.367). COAs show strong loadings on their respective latent constructs. Conclusions: The CDM identifies itch severity as a central driver of the patient burden in moderate-to-severe AD and supports prioritization of itch and sleep disturbance in clinical assessment, therapeutic planning, and outcome evaluation in AD. Our model, whose validity is strengthened by expert consensus, can potentially guide clinical decision-making and evaluation of treatment responses across key domains of AD burden. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s13555-026-01905-9.
SN - 2193-8210
SN - 2190-9172
ER -