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

INTRODUCTION: The global burden of atopic dermatitis (AD) will continue to rise in the coming two decades, underscoring the need for affordable and globally accessible therapies given restricted access to high-cost medications in many regions. The study aimed to evaluate the efficacy of a novel phototherapy-based regimen as an add-on therapy, together with vitamin D supplementation, on long-term disease control in AD. METHODS: The PRADA trial combined two independent randomizations within the same population: an open-label, crossover comparison of narrowband ultraviolet B (NB-UVB) phototherapy versus observation, and a double-blind, parallel-group comparison of vitamin D versus placebo, both superimposed on standard topical anti-inflammatory treatments (TAT). It was conducted between 2015 and 2023 across 16 French hospital centers. The trial included patients aged ≥ 15 years with moderate-to-severe (IGA > 2) AD and with fewer than 100 lifetime phototherapy sessions. The primary outcome was a hierarchical composite endpoint based on: (1) repeated measures of Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) severity score over 1 year; and (2) the cumulative use of TAT from October to March. RESULTS: A total of 53 participants were allocated to the vitamin D (26 received NB-UVB during the first period), and 57 to the placebo (27 received NB-UVB during the first period). A total of 93 participants were available for the main analysis for the primary endpoint. Vitamin D was significantly associated with lower PO-SCORAD scores compared with placebo (mean [95% CI] difference -5.6 [-12.1 to -1.78]), however, this effect size remained below the prespecified minimum clinically important difference (nine points). NB-UVB showed no significant effect on PO-SCORAD scores (mean difference: 1.25 [-3.90 to 1.40]). Adverse event incidence was 0.33 per 100 patient-months, mainly nonserious photosensitivity reactions (n = 38). CONCLUSIONS: In the PRADA trial (underpowered due to a recruitment short fall), NB-UVB phototherapy showed no clinically meaningful benefit on the long-term control of moderate-to-severe AD. The observed benefit of vitamin D supplementation on PO-SCORAD, although statistically significant, did not reach the threshold for clinical relevance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537509.

INTRODUCTION: Upadacitinib and dupilumab are both approved treatments for moderate-to-severe atopic dermatitis (AD). Some dupilumab-treated patients may experience an inadequate response and/or safety/tolerability issues. Real-world data on the effectiveness of upadacitinib in this population remain limited. The objective was to evaluate the effectiveness and safety of upadacitinib in adults diagnosed with moderate-to-severe AD who were inadequate responders to dupilumab or discontinued dupilumab for safety/tolerability reasons. METHODS: CAN UpTIMISE was a Canadian prospective, observational study in adults treated with dupilumab for moderate-to-severe AD with a decision to switch to upadacitinib (15/30 mg), per local label. Effectiveness was assessed over 4 months using the validated Investigator Global Assessment for AD (vIGA-AD), facial IGA, Eczema Area and Severity Index (EASI), Worst Pruritus Numerical Rating Scale (WP-NRS), Dermatology Life Quality Index (DLQI), and Patient Oriented Eczema Measurement (POEM). Results are presented using descriptive statistics. RESULTS: Among 108 patients (94.4% with vIGA-AD ≥ 2), 83.3% discontinued dupilumab due to inadequate effectiveness and 16.7% discontinued due to safety/tolerability reasons. At month 4, 65.9% (95% CI 55.1-75.2) achieved vIGA-AD 0/1 by observed case analysis (primary outcome), with improvements evident as early as month 1. At month 4 after upadacitinib initiation, 90.2%, 82.9%, and 52.4% of patients achieved EASI ≤ 7, ≤ 3, and ≤ 1, respectively; 70.5% with baseline WP-NRS > 4 had ≥ 4-point reduction and 46.7% reported WP-NRS 0/1. DLQI and POEM scores improved similarly, with 36.0% and 34.3%, respectively, achieving scores indicating no impact or clear/almost clear disease. Minimal disease activity (EASI ≤3 and WP-NRS 0/1) was reached by 43.8% of patients. Upadacitinib was generally well tolerated and no new safety signals were identified. CONCLUSIONS: Upadacitinib provided rapid, clinically meaningful, and generally sustained improvements in disease activity, itch, and quality of life, supporting its role as an effective and well-tolerated treatment for patients with inadequate response or intolerance to dupilumab in real-world practice. Graphical abstract available for this article. TRIAL REGISTRATION: NCT05394792.