Clinical Trial Eligibility in Atopic Dermatitis: Data from a Large Real-World International Cohort

INTRODUCTION: Randomized clinical trials (RCTs) in atopic dermatitis (AD) often exclude older adults and patients with comorbidities, limiting the generalizability of trial findings to real-world populations. Despite the growing use of biologics and Janus kinase inhibitors (JAKis) in clinical practice, the extent to which real-world patients meet RCT eligibility criteria and their associated safety outcomes remains unclear. METHODS: We conducted a retrospective analysis of a large, multicenter international cohort of adolescents and adults with AD treated with biologics (dupilumab, tralokinumab) or systemic JAKis (abrocitinib, baricitinib, upadacitinib) between October 2017 and March 2023 across 16 dermatology centers. Eligibility was defined according to commonly applied RCT criteria. Patients meeting ≥ 1 exclusion criterion were classified as ineligible. Demographic, clinical, and safety outcomes were analyzed. RESULTS: Among 2154 patients, 514 (23.9%) were ineligible. The most frequent reasons were Eczema Area and Severity Index (EASI) < 16 (67.9%), age ≥ 75 years (21.8%), and cardiovascular disease (13.0%). Ineligibility patterns differed across treatments: patients receiving JAKis were most often ineligible because of EASI < 16 (92.8%), whereas ineligibility among biologic users more commonly reflected also age or cardiovascular comorbidity. Ineligible patients were older, had more non-atopic comorbidities, and had lower measured baseline disease activity. Safety profiles were generally favorable. Among biologic-treated patients, adverse event rates were similar between eligible and ineligible groups. In the JAKi cohort, overall adverse events were more frequent in ineligible patients (52.9% vs. 42.6%; p = 0.051), with acneiform eruption and lipid abnormalities emerging as the most distinct differences. No unexpected safety signals were identified in either treatment group. CONCLUSION: Nearly one-quarter of real-world patients with AD would not have met eligibility criteria for pivotal RCTs, yet both biologics and JAK inhibitors demonstrated acceptable safety profiles in these populations. While adverse events were more frequent among ineligible patients receiving JAKis, findings require further investigation to determine their clinical relevance, particularly regarding long-term cardiovascular outcomes.