619 - Lebrikizumab improves signs and symptoms of moderate-to-severe atopic dermatitis in patients not adequately controlled or non-eligible for cyclosporine: a placebo-controlled, randomized phase 3 clinical study (ADvantage)
Bibliographic record
Abstract
Abstract Introduction Lebrikizumab (LEB), a novel monoclonal antibody with high affinity and slow off-rate to interleukin-13, is efficacious and safe in adults and adolescents with moderate-to-severe atopic dermatitis (AD). Efficacy of cyclosporine A (CsA), used for severe AD, may not be optimal in some AD patients and its safety limits long-term use. Objectives We report 16-week efficacy and safety of LEB + low-/mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD, not adequately controlled/non-eligible for CsA, in the phase 3 ADvantage study. Methods ADvantage had a 16-week, randomized, double-blind, PBO-controlled, parallel-group period followed by a 36-week open-label maintenance period. Eligibility: adults and adolescents (age ≥12 - <18 years), Eczema Area and Severity Index (EASI) ≥16, Investigator’s Global Assessment (IGA) ≥3, ≥10% body surface area of AD involvement, and patients not adequately controlled or non-eligible for CsA. Randomization: 2:1 to LEB 250 mg with a loading dose of LEB 500 mg at baseline and week-2, or PBO every two weeks (Q2W). All patients received concomitant mid-potency TCS through week-16; dosage tapered once lesions were controlled and stopped after 7 days. Primary endpoint: percentage of patients achieving 75% reduction in EASI (EASI 75) at week-16. Secondary endpoints: percentage of patients achieving EASI 90, IGA 0/1, and ≥4-point improvement in pruritus Numeric Rating Scale (NRS) at week-16. Safety endpoints: treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and TEAEs causing discontinuation. Results 312/331 patients (212 LEB+TCS and 100 PBO+TCS) completed the 16-week period. At week 16, significantly higher proportion of LEB+TCS vs PBO+TCS patients achieved EASI 75 (68.4% vs 40.8%, p<0.001) and EASI 90 (42.9% vs 20.8%, nominal p<0.001); higher percentage of patients achieved IGA 0/1 (42.0% vs 24.5%, nominal p<0.01) and ≥4-point improvement in pruritus NRS (49.9% vs 29.7%, nominal p<0.05). TEAEs: 61.8% LEB+TCS vs 53.2% PBO+TCS, with nasopharyngitis and conjunctivitis being the most common TEAEs. SAEs and TEAEs causing discontinuation were low and similar in both groups. Conclusions At week 16, LEB 250 mg Q2W + TCS significantly improved AD signs and symptoms in adults and adolescents with moderate-to-severe AD and history of inadequate response to CsA, or for whom CsA was not advisable.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".