524 - Efficacy of upadacitinib and dupilumab on achieving stringent and composite skin and itch outcomes: an indirect comparison of adults with moderate-to-severe atopic dermatitis
Bibliographic record
Abstract
Abstract Introduction/Background Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and Measure Up 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-to-head trial against dupilumab 300mg. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated stringent and composite measures of efficacy. Objectives To indirectly compare upadacitinib and dupilumab on stringent and composite measures of skin clearance and itch resolution. Methods A population-adjusted indirect comparison using covariate adjustment as a treatment effect calibration was conducted using individual patient data from Measure Up 1 and 2 and Heads Up. Specifically, the indirect comparison model estimated how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates (age, gender, race, country, previous use of systemic therapy, disease duration, baseline validated Investigator Global Assessment scale for AD score, and baseline Eczema Area and Severity Index [EASI]). Absolute response rates at weeks 4 and 16 were estimated for the following outcomes: no/minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1), 100% improvement in EASI (EASI 100), achievement of both ≥90% improvement in EASI (EASI 90) and WP-NRS 0/1, and achievement of both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to-treat population for the clinical trials, and utilized non-responder imputation. Results Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg, and then dupilumab. This pattern was observed at week 4 on the achievement of WP-NRS 0/1 (upadacitinib 30 mg: 34.2% | upadacitinib 15 mg: 18.2% | dupilumab: 7.9%), EASI 100 (8.5% | 4.7% | 1.8%), EASI 90 & WP-NRS 0/1 (21.9% | 10.6% | 3.3%), and EASI 100 & WP-NRS 0/1 (6.4% | 3.5% | 1.2%). This ranking was maintained at week 16 for WP-NRS 0/1 (35.4% | 22.5% | 16.2%), EASI 100 (28.4% | 22.2% | 7.9%), EASI 90 & WP-NRS 0/1 (32.2% | 19.6% | 12.4%), and EASI 100 & WP-NRS 0/1 (19.6% | 12.7% | 4.2%). Conclusions For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining stringent and composite outcomes after 4 and 16 weeks, followed by upadacitinib 15 mg, and then dupilumab.
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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 | 0.011 | 0.020 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.014 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.011 | 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".