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Background: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate‐to‐severe AD. Methods: MEASURE‐AD was a cross‐sectional 28‐country study in patients with physician‐confirmed moderate‐to‐severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP‐NRS; range: 0–10) and Dermatology Life Quality Index (DLQI; range: 0–30) and Children's DLQI (CDLQI; range: 0–30). Secondary outcomes included physician‐ and patient‐reported clinical, psychosocial and economic burden. Results: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP‐NRS was 5.3 in the total population, and most patients (≥55%) reported moderate‐to‐severe pruritus (WP‐NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications. Conclusions: While systemic therapy lowers overall disease burden, patients with moderate‐to‐severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD. [ABSTRACT FROM AUTHOR]