特应性皮炎（AD）前沿文献精读特辑（Clin Exp Dermatol / Dermatol Ther (Heidelb)）

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disease clinically characterized by eczematous lesions and severe itch, significantly affecting the patients' quality of life. AD is classified as mild, moderate, or severe according to the extent and severity of these lesions. While therapeutic protocols for mild and severe AD are well-defined, the moderate stage represents a clinical 'gray zone' characterized by inconsistent management. It is frequently mismanaged, oscillating between undertreatment and the indiscriminate use of traditional systemic therapies. The moderate stage of AD requires a tailored approach to maximize topical treatments efficacy, avoid the side effects of systemic drugs, while remaining ready to escalate therapy if needed. METHODS: An Italy-based, expert-Delphi consensus was used to: (1) reach a consensus on moderate AD classification criteria; (2) characterize the disease-specific burden in these patients; (3) identify key elements and concerns in moderate AD treatment; and (4) identify the therapeutic and management-related unmet needs of this subset of patients. RESULTS: Agreement was reached for 26 final statements, which included highlighting a significant disease burden also for patients with moderate AD. CONCLUSIONS: The findings underscore a misalignment between the actual disease burden of moderate AD and current regulatory reimbursement criteria. In Italy, the restricted access to innovative systemic therapies for this specific patient population represents a critical healthcare gap.

INTRODUCTION: Lebrikizumab provides lasting improvements in skin clearance and itch relief in patients with moderate-to-severe atopic dermatitis (AD). This analysis assessed long-term stability, depth of response, and flare incidence through 3 years in week 16 responders from ADvocate1 and ADvocate2 who continued maintenance lebrikizumab regimen (every 4 weeks [Q4W] or every 2 weeks [Q2W]) in the ADjoin extension study. METHODS: Responders achieved either an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥ 2-point improvement or ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16, without rescue medication use. Long-term deep response was defined by skin and itch endpoints (3 years: IGA 0, ≥ 90% improvement from baseline in EASI [EASI 90], 100% improvement from baseline in EASI [EASI 100], absolute EASI score of ≤ 1 [EASI ≤ 1], Patient-Oriented Eczema Measure [POEM] [0, 1], POEM itch [0, 1]; 2 years: Pruritus Numeric Rating Scale [0, 1]). Stability was defined as maintaining outcomes at ≥ 80% of attended visits between week 16 and week 152. Flares were evaluated via three definitions: any rescue therapy use, high-potency topical corticosteroids or systemic intervention, or adverse events due to AD exacerbation. RESULTS: After 152 weeks of continuous treatment, 88.6% (Q4W) and 80.0% (Q2W) of week 16 responders maintained EASI 90, while 64.3% (Q4W) and 68.8% (Q2W) maintained EASI 100. Most patients achieving EASI 90 or EASI 100 at week 16 maintained stable responses through week 152 (Q4W: 77.8% and 57.9%; Q2W: 81.1% and 63.6%, respectively). Among stable EASI 75 responders (Q4W), 72.8% did not experience any flare through week 152, with an incidence rate of 0.19 flares per patient-year (~1 flare every 5 patient-years). Improvements in itch outcomes were sustained over time and followed patterns similar to those observed for skin responses. CONCLUSIONS: Continuous lebrikizumab treatment through 3 years provided stable disease control in skin and itch symptoms, with infrequent flares experienced by week 16 responders with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04146363, NCT04178967, and NCT04392154.