Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease. Lebrikizumab, a monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in previous Phase 3 trials: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), and ADhere (NCT04250337). We report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open-label study of lebrikizumab in adolescent patients with moderate-to-severe AD. The primary endpoint was to describe the proportion of patients who discontinued from study treatment because of adverse events (AEs) through the last treatment visit. Adolescent patients (N = 206) (≥ 12 to < 18 years old, weighing ≥ 40 kg) with moderate-to-severe AD received subcutaneous lebrikizumab 500 mg loading doses at baseline and Week 2, followed by 250 mg every 2 weeks (Q2W) thereafter. Safety was monitored using reported AEs, AEs leading to treatment discontinuation, vital signs, growth assessments, and laboratory testing. Efficacy analyses included Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Body Surface Area (BSA), (Children’s) Dermatology Life Quality Index ((C)DLQI), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression. 172 patients completed the treatment period. Low frequencies of SAEs (n = 5, 2.4%) and AEs leading to treatment discontinuation (n = 5, 2.4%) were reported. Overall, 134 patients (65%) reported at least one treatment-emergent AE (TEAE), most being mild or moderate in severity. In total, 62.6% achieved IGA (0,1) with ≥ 2-point improvement from baseline and 81.9% achieved EASI-75 by Week 52. The EASI mean percentage improvement from baseline to Week 52 was 86.0%. Mean BSA at baseline was 45.4%, decreasing to 8.4% by Week 52. Improvements in mean change from baseline (CFB) to Week 52 were observed in DLQI (baseline 12.3; CFB − 8.9), CDLQI (baseline 10.1; CFB − 6.5), PROMIS Anxiety (baseline 51.5; CFB − 6.3), and PROMIS Depression (baseline 49.3; CFB − 3.4) scores. Lebrikizumab 250 mg Q2W had a safety profile consistent with previous trials and significantly improved AD symptoms and quality of life, with meaningful responses at Week 16 increasing by Week 52. ClinicalTrials.gov identifier, NCT04250350. Atopic dermatitis is a chronic relapsing inflammatory skin disease that affects up to 15% of adolescents worldwide, with up to 50% suffering from moderate-to-severe disease. Signs and symptoms include dry, cracked skin; redness; itching; and painful lesions, which can negatively affect quality of life and lead to complications, including skin infections. Adolescents also report increased rates of anxiety and stress. Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, the key cytokine in atopic dermatitis, blocking the downstream effects of IL-13 with high potency. Lebrikizumab has been shown previously to improve symptoms of atopic dermatitis, including itch, skin clearance, and quality of life in ADvocate1, ADvocate2 and ADhere. The ADore study aimed to evaluate the safety and efficacy of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. Investigators recruited patients ≥ 12 to < 18 years old, weighing ≥ 40 kg, from Australia, Canada, Poland, and the US who were diagnosed with moderate-to-severe atopic dermatitis. These patients received a loading dose of 500 mg of lebrikizumab at Weeks 0 and 2, followed by 250 mg every 2 weeks for 52 weeks. The safety profile of lebrikizumab was consistent with previously published reports, with mostly mild or moderate adverse events, which did not lead to treatment discontinuation. Lebrikizumab improved skin clearance; 62.6% of patients had clear or almost clear skin by the end of the trial. Lebrikizumab also improved the patients’ quality of life. These safety and efficacy results support lebrikizumab’s role in treating adolescents with moderate-to-severe atopic dermatitis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it