Efficacy and safety of upadacitinib versus dupilumab in adults and adolescents with moderate-to-severe atopic dermatitis: week 16 results of an open-label randomized efficacy assessor-blinded head-to-head phase IIIb/IV study (Level Up).

Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients with AD continue to experience flares and substantial clinical burden, despite ongoing systemic treatment. To assess the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) as per its label, and present the week 16 primary analysis results. Level Up is a phase IIIb/IV global randomized open-label efficacy assessor-blinded study evaluating UPA vs. DUPI in adolescents and adults with moderate-to-severe AD who had an inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (period 1). Patients on UPA were started on 15 mg and dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥ 4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on or after week 4, or an EASI reduction of at least 75% (EASI 75) on or after week 8. The primary endpoint was simultaneous achievement of an EASI reduction of at least 90% (EASI 90) and WP-NRS 0/1 at week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study. Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at week 16 was demonstrated with UPA vs. DUPI (19.9% vs 8.9%, respectively; P < 0.001). UPA showed superiority over DUPI for all ranked secondary endpoints, with post hoc analyses exhibiting higher itch response rates as early as day 2. No new safety signals were identified in this period. Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose-escalated based on clinical response, demonstrated superiority over DUPI per its label for the primary endpoint of simultaneous achievement of near-complete skin clearance (EASI 90) and little-to-no itch (WP-NRS 0/1) at week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. No new safety signals were identified vs. the previously reported safety profiles of UPA and DUPI.

Silverberg JI ，Bunick CG ，Hong HC ，Mendes-Bastos P ，Stein Gold L ，Costanzo A ，Ibrahim N ，Sancho C ，Wu X ，Han Y ，Levy G ，Altman K ，Calimlim B ，Eyerich K ... -  《-》

Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis.

Edwards SJ ，Karner C ，Jhita T ，Barton S ，Marceniuk G ，Yiu ZZN ，Wittmann M ... -  《-》

Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis: Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks.

Paller AS ，Mendes-Bastos P ，Siegfried E ，Eichenfield LF ，Soong W ，Prajapati VH ，Lio P ，Simpson EL ，Raymundo EM ，Suravaram S ，Hu X ，Yang Y ，Huang X ，Calimlim BM ，Platt AM ，Su JC ，Zheng M ，Yamamoto-Hanada K ，Teixeira HD ，Irvine AD ... -  《-》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

One-Year Insights into the GLOBOSTAD Multinational Prospective Observational Study of Patients Receiving Dupilumab for Atopic Dermatitis.

Currently, limited data are available on long-term use of dupilumab to treat atopic dermatitis (AD) in a multinational real-world setting. The aim of this analysis was to report the interim 1-year data for patients with AD enrolled in the GLOBOSTAD registry, including treatment patterns, dupilumab effectiveness and safety, and healthcare burden. GLOBOSTAD is an ongoing, 5-year, multinational, prospective, observational study of adult/adolescent (aged ≥ 12 years at baseline) patients with AD who initiated dupilumab in real-world settings according to their local country-specific prescribing guidelines. Outcomes were evaluated at baseline and at 3, 6 and 12 months and included Eczema Area and Severity Index (EASI) total score, SCORing Atopic Dermatitis (SCORAD) total score, percent body surface area (BSA) affected, Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI) total score for adults or Children's Dermatology Life Quality Index (CDLQI) total score for adolescents and pruritus Numeric Rating Scale (NRS) total score. At the interim 1-year cut-off (March 2023), 955 patients were enrolled in GLOBOSTAD, and follow-up data were obtained from 903 patients. After dupilumab initiation, mean improvements in effectiveness outcome measures from baseline to month 3 were EASI from 25.1 to 6.1, SCORAD 59.3 to 25.3, POEM 19.7 to 8.7, DLQI 13.7 to 5.3, CDLQI 12.2 to 2.7 and pruritus NRS 6.3 to 2.5, with each measure exceeding the minimal clinically important difference. These positive changes in effectiveness outcomes were maintained or further improved through 12 months since treatment initiation. AD-related hospitalizations and emergency room or urgent care facility visits decreased from 11.1% to 1.7% from baseline to month 12. In a multinational real-world setting, dupilumab demonstrated rapid, robust and sustained effectiveness in patients with moderate-to-severe AD across multiple disease domains, including AD signs, symptoms, quality of life and emergency/urgent care visits. Safety was consistent with the known dupilumab safety profile. ClinicalTrials.gov Identifier NCT03992417.

Calzavara-Pinton P ，Chu CY ，Lapeere H ，Rossi M ，Ferrucci SM ，Chung WH ，Fougerousse AC ，Fomina DS ，Holzer G ，Čelakovská J ，Al-Ahmad M ，Tzellos T ，Wu J ，Ardeleanu M ，Bosman K ... -  《-》