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Inclusion of Older Adults in Randomized Clinical Trials for Systemic Medications for Atopic DermatitisA Systematic Review

Educational Objective
To examine the representation of older adults in clinical trials of systemic immunomodulatory therapies for atopic dermatitis.
1 Credit CME
Key Points

Question  Do randomized clinical trials investigating systemic immunomodulatory therapies for atopic dermatitis in adults include older participants?

Findings  In this systematic review including 32 trials with 4547 participants, 11 trials (34%) reported explicit upper age limits. Seven trials reported the proportion of older adults among participants; in these trials, 112 of 2963 participants (4%) were aged 65 years or older.

Meaning  These findings suggest that older adults are underrepresented in trials of systemic immunomodulatory treatment for atopic dermatitis, which casts doubt on the generalizability of the current evidence base to that population; future trials should endeavor to increase older adult participants and perform age-stratified analyses for treatment safety and efficacy.

Abstract

Importance  Despite increasing evidence that atopic dermatitis is common in older adults, it is unclear whether the evidence base for treating atopic dermatitis with systemic therapy is generalizable to that population. Older adults are most at risk for adverse events from medications, given age-related alterations in drug metabolism, increased comorbidity, and polypharmacy.

Objective  This systematic review examines the representation of older adults in randomized clinical trials (RCTs) of systemic immunomodulatory treatments for atopic dermatitis and whether safety and efficacy data are reported specifically for older individuals.

Evidence Review  The Cochrane Central Register of Controlled Trials, Embase, MEDLINE databases, and the ClinicalTrials.gov trial register were searched from inception (MEDLINE via Ovid, 1946; Embase via Ovid, 1974) to November 7, 2019. RCTs investigating systemic immunomodulatory treatments for adults with atopic dermatitis were included. Titles, abstracts, and full-text papers were screened, and data were extracted in duplicate.

Findings  A total of 32 trials with 4547 participants were reviewed. The mean (SD) age of trial participants was 34.4 (5.4) years. The median number of participants per trial was 44 (range, 10-740). Eleven trials (34%) reported explicit upper age limits ranging from 42 to 70 years of age. Most of these trials (n = 9) examined safety and effectiveness of cyclosporine. Twenty-two trials (69%) had other exclusion criteria that might disproportionately exclude older adults. In total, 10 trials (31%) included adults aged 65 years or older. Within 7 trials that reported the proportion of participants aged 65 and older (all evaluating dupilumab), 112 of 2964 participants (4%) were 65 years or older. None of the included trials reported stratified safety or effectiveness data for older adults.

Conclusions and Relevance  Study results suggest that older adults are underrepresented in RCTs of systemic treatment for atopic dermatitis, resulting in a lack of evidence supporting safe clinical use for older adults. Clinicians and patients should be aware of this evidence gap when prescribing systemic therapy for atopic dermatitis. Randomized trials and observational studies that include older patients with atopic dermatitis are needed.

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Article Information

Accepted for Publication: June 15, 2020.

Published Online: August 19, 2020. doi:10.1001/jamadermatol.2020.2940

Correction: This article was corrected on September 30, 2020, to fix a value that was incorrectly reported in the Findings section of the Abstract.

Corresponding Author: Aaron M. Drucker, MD, ScM, Division of Dermatology, Women’s College Hospital, 76 Grenville St, Toronto, ON M5S1B2, Canada (aaron.drucker@wchospital.ca).

Author Contributions: Ms Lam had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Maqbool, Drucker.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Lam, Rochon.

Critical revision of the manuscript for important intellectual content: Zhu, Maqbool, Adam, Tadrous, Drucker.

Statistical analysis: Lam.

Administrative, technical, or material support: Zhu, Adam.

Supervision: Drucker.

Conflict of Interest Disclosures: Dr Drucker reported receiving institutional research funding from Sanofi and institutional research funding from Regeneron outside the submitted work; consulting fees in the last 3 years from Sanofi, RTI Health Solutions, the Eczema Society of Canada, and the Canadian Agency for Drugs and Technology in Health; honoraria from Prime Inc, CME Outfitters, and the Eczema Society of Canada; and educational grants from Sanofi and research grants from Sanofi and Regeneron. No other disclosures were reported.

Additional Contributions: We thank Hannah McIntosh, BScH, for her assistance with literature retrieval. There was no financial compensation for this contribution.

Additional Information: Gustavo Cordova, MD, was listed as an investigator in the registered protocol and acted as an abstract screener but did not meet criteria for authorship.

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