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Record W4401436023 · doi:10.1093/bjd/ljae266.091

718 - Dupilumab reduces the number of lesions in adult patients with prurigo nodularis presenting with multiple lesion morphologies: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

2024· article· en· W4401436023 on OpenAlexaff
Sonja Ständer, Gil Yosipovitch, Brian Kim, Hwanhee Hong, Martin Metz, Hiroyuki Murota, Xing-Hua Gao, Marjolein de Bruin‐Weller, Amy Praestgaard, Joseph Zahn, Simmi Wiggins

Bibliographic record

VenueBritish Journal of Dermatology · 2024
Typearticle
Languageen
FieldMedicine
TopicAutoimmune Bullous Skin Diseases
Canadian institutionsProbity Medical ResearchUniversity of British Columbia
Fundersnot available
KeywordsDupilumabMedicinePrurigo nodularisPlaceboAdverse effectLesionEczema Area and Severity IndexClinical trialInternal medicineAtopic dermatitisDermatologyDermatology Life Quality IndexSurgeryPathologyDisease

Abstract

fetched live from OpenAlex

Abstract Introduction/Background Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by itchy skin lesions presenting as nodules, papules, plaques, or ulcers. These different clinical morphologies may present simultaneously and an individual patient may exhibit different morphologic variants over time. Dupilumab is the first systemic treatment approved by the US Food and Drug Administration and European Medicines Agency for the treatment of adults with PN. LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two phase 3 randomized placebo-controlled clinical trials that demonstrated the efficacy and safety of dupilumab in adults with PN inadequately controlled with topical medications or for whom those were inadvisable. Objectives To report baseline lesion morphologies and the effect of dupilumab on the number of skin lesions present, as measured by the Prurigo Activity and Severity (PAS) score, in patients with PN presenting with multiple lesion morphologies. Methods In LIBERTY-PN PRIME and PRIME2, patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks over 24 weeks. PAS, a simplified 5-item questionnaire, was used to assess the types of lesions present (PAS Item 1a) and the numbers of lesions in a representative body area (PAS Item 4). Safety endpoints included treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs). Data from both studies were pooled and comparisons analyzed using analysis of covariance. Results All patients in PRIME and PRIME2 had nodules and an Investigator’s Global Assessment for PN-Stage (IGA PN-S) score of 3 or 4 at baseline. Additional PN lesion types included papules (dupilumab: 69.9%, placebo: 69.4% at baseline), hypo- or hyper-pigmented macules (dupilumab: 50.3%, placebo: 55.4%), plaques (dupilumab: 30.7%, placebo: 39.5%), and ulcers (dupilumab: 32.0%, placebo: 28.7%). At least 2 types of lesions at baseline were reported by 77.1% of the dupilumab group and 79.0% of the placebo group, while 10.5% of the dupilumab and 13.4% of the placebo group reported 5 concomitant lesion types at baseline (nodules, papules, hypo- or hyper-pigmented macules, ulcers, and plaques). After 24 weeks of treatment, 3.3% of patients given dupilumab and 7.6% of patients given placebo reported 5 types of concomitant lesions. Dupilumab reduced the overall number of lesions (SD) in a representative area of the body by 61.1% (45.7) at Week 24, compared with a 22.9% (63.3) reduction in the placebo group. Treatment-emergent adverse events (TEAEs) occurred in 91 (59.9%) and 80 (51.0%) patients from the dupilumab and placebo groups, respectively. TEAEs leading to discontinuation occurred in 0 patients given dupilumab and 3 (1.9%) given placebo. Conclusions Patients with PN experienced a high baseline lesion burden; >75% of patients reported ≥2 types of concomitant lesions, and >10% of patients reported 5 types of concomitant lesions. Dupilumab treatment reduced the number of lesions and the percentage of patients reporting 5 concomitant lesion morphologies. Safety data were generally consistent with the known safety profile of dupilumab.

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.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.098
Threshold uncertainty score0.608

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.020
GPT teacher head0.311
Teacher spread0.291 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

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Citations0
Published2024
Admission routes1
Has abstractyes

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