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)
Bibliographic record
Abstract
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Randomized trial | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Randomized trial | high |
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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| 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, unvalidatedLabeled directly by 2 models reading the full record.
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".