734 - Efficacy and safety of upadacitinib vs dupliumab in adults and adolescents with moderate-to-severe atopic dermatitis: results of an open-label, efficacy assessor-blinded head-to-head phase 3b/4 study (Level Up)
Bibliographic record
Abstract
Abstract Introduction/Background Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and eczematous skin lesions. Some patients with AD continue to experience flares and substantial clinical burden despite the use of systemic therapy. Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 versus JAK2, JAK3, and tyrosine kinase 2. Dupilumab is a monoclonal antibody inhibiting interleukin-4 and interleukin-13 signaling. Both upadacitinib and dupilumab are approved in multiple countries for the treatment of moderate-to-severe AD in adolescents and adults. Objectives This monotherapy study assessed the efficacy and safety of upadacitinib, initiated at 15 mg once daily (QD) and dose-escalated to 30 mg QD based on clinical response, compared with dupilumab per its label. Results presented here are based on the Week 16 primary analysis. Methods Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded, head-to-head, multi-center study evaluating upadacitinib vs dupilumab in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use of those therapies was inadvisable. Patients were randomized to upadacitinib 15 mg or dupilumab per its label for 16 weeks of treatment (Period 1), with an extension period to 32 weeks (Period 2) for patients not achieving at least 75% reduction in Eczema Area and Severity Index from baseline (EASI 75) at Week 16. Patients on upadacitinib 15 mg were dose-escalated to 30 mg starting from Week 4 if they had a Results A total of 920 patients (803 adults, 117 adolescents) were randomized to upadacitinib (458) or dupilumab (462). At Week 16, upadacitinib showed superior efficacy versus dupilumab in the primary endpoint, where a significantly higher proportion of patients simultaneously achieved EASI 90 and WP-NRS 0/1 at Week 16 (19.9% vs 8.9% for upadacitinib and dupilumab respectively, p<0.0001). Upadacitinib also showed superiority versus dupilumab for all ranked secondary endpoints including skin and itch response endpoints at varying response levels and timepoints. No new safety signals were identified during Period 1. Proportions of patients with any treatment-emergent adverse event were higher for upadacitinib (65.3%) than dupilumab (52.7%). Severe adverse events (AEs) and AEs leading to discontinuation of study treatment were similar between upadacitinib and dupilumab, with no difference in the proportion of serious AEs (0.9%). The most common AE reported was nasopharyngitis for both upadacitinib and dupilumab. One serious infection (0.2%) was reported for dupilumab, and none for upadacitinib. Five opportunistic infections (excluding tuberculosis and herpes zoster) occurred for upadacitinib (all eczema herpeticum) with none for dupilumab. No malignancies, adjudicated major adverse cardiac events, adjudicated venous thromboembolic events (VTEs) or deaths were reported in either treatment group. Conclusions Treatment of moderate-to-severe AD with upadacitinib demonstrated superiority versus dupilumab for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and no to little itch (WP-NRS 0/1) at Week 16 and for all ranked secondary endpoints. There were no new safety risks compared to the known safety profile of upadacitinib.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".