@article{1b8742490d5a476e8e80fb0a734f50ae,
title = "Definition of Clinically Meaningful Within-Patient Changes in POEM and CDLQI in Children 6 to 11 Years of Age with Severe Atopic Dermatitis",
abstract = "Introduction: The Patient-Oriented Eczema Measure (POEM) assesses patient-reported severity of atopic dermatitis (AD) symptoms, whereas the Children{\textquoteright}s Dermatology Life Quality Index (CDLQI) measures how AD affects health-related quality of life (HRQoL) in children. Although the POEM and CDLQI have established thresholds for clinically meaningful within-patient change in adolescents (aged 12–17 years), there are no defined within-patient responder thresholds for clinically meaningful change in children aged 6–11 years. Methods: Data from the LIBERTY AD PEDS phase 3 randomized, double-blind, placebo-controlled trial of dupilumab in children aged 6–11 years with severe AD were used to define the threshold for within-patient meaningful change in POEM and CDLQI scores. Anchor-based methods were applied to estimate mean change in POEM and CDLQI scores from baseline to week 16, with anchors of a 1-point improvement in the Patient Global Impression of Disease (PGID) scale and an improvement in score of {\textquoteleft}{\textquoteleft}A little better{\textquoteright}{\textquoteright} on the Patient Global Impression of Change (PGIC) scale. The distribution-based methods, a one-half standard deviation (SD) at baseline and a standard error mean (SEM) were also used. Results: The mean POEM change scores associated with the anchors were a change of − 8.40 with the PGID anchor and − 6.30 with the PGIC anchor. Distribution-based estimates for POEM were one-half SD at baseline of 2.76, with a SEM of 3.32. Mean CDLQI change scores corresponding to the PGID and PGIC anchors were − 7.30 and − 6.80, respectively, while distribution-based estimates for CDLQI were a one-half SD at baseline of 3.69, with a SEM of 3.52. Conclusions: In children with severe AD, an appropriate minimum threshold of clinically meaningful within-patient change was estimated as 6 points for both the POEM and CDLQI scores. Trial registration: ClinicalTrials.gov Identifier: NCT03345914. [MediaObject not available: see fulltext.]",
keywords = "Atopic dermatitis, CDLQI, Clinically meaningful, Dupilumab, POEM, Pediatric, Psychometric, Responder threshold, Validation",
author = "Simpson, {Eric L.} and {de Bruin-Weller}, Marjolein and Ashish Bansal and Zhen Chen and Lauren Nelson and Diane Whalley and Randy Prescilla and Isabelle Guillemin and Dimittri Delevry",
note = "Funding Information: The study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The journal Rapid Service Fee was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Funding Information: The study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The journal Rapid Service Fee was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Medical writing and editorial assistance provided by Juliet Bell, PhD, and Liselotte van Delden, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors contributed to manuscript concept and design. ELS and MdB-W acquired data. ZC conducted the statistical analyses on the data. All authors interpreted the data, provided critical feedback on the manuscript, approved the final manuscript for submission, and are accountable for the accuracy and integrity of the manuscript. The authors acknowledge Dr. Abhijit Gadkari and Dr. Laurent Eckert for earlier contributions to the study design and data analysis. Eric L. Simpson reports personal fees from AbbVie, Boehringer-Ingelheim, Collective Acument LLC, Eli Lilly, Forte Bio, Incyte, Janssen, Kyowa Hakko Kirin, Leo Pharma, Novartis , Ortho Dermatologics, Pfizer, Pierre Fabre Dermo Cosmetique, Regeneron, Roivant, Sanofi and Valeant; and reports grants (or Principal Investigator role) from AbbVie, Eli Lilly, Incyte, Kyowa Hakko Kirin, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Tioga, and Vanda. Marjolein de Bruin-Weller has been Principal Investigator, advisory board member, and consultant for Regeneron Pharmaceuticals, Inc., Sanofi Genzyme; Principal Investigator and advisory board member for AbbVie and Pfizer; and advisory board member for Eli Lilly and UCB. Ashish Bansal is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Zhen Chen is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Lauren Nelson and Diane Whalley are employees of RTI Health Solutions, which received funding from Regeneron Pharmaceuticals, Inc. Randy Prescilla is an employee of Sanofi Genzyme, may hold stock and/or stock options in Sanofi. Isabelle Guillemin was an employee of Sanofi at the time of the research, may hold stock and/or stock options in Sanofi. Dimittri Delevry is an employee and shareholder of Regeneron Pharmaceuticals, Inc. The study was conducted in accordance with the provisions of the Declaration of Helsinki, the International Council for Harmonisation Good Clinical Practice (ICH GCP) guideline, and applicable regulatory requirements; the protocol was reviewed and approved by institutional review boards/ethics committees. For all patients, written informed consent was obtained from a parent or legal guardian, and written informed assent was obtained from the patient. Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in this manuscript. Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification. Requests should be submitted to https://vivli.org/. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = aug,
doi = "10.1007/s13555-021-00543-7",
language = "English (US)",
volume = "11",
pages = "1415--1422",
journal = "Dermatology and Therapy",
issn = "2190-9172",
publisher = "Springer Verlag",
number = "4",
}