Vixarelimab in Patients With Prurigo Nodularis
Notice bibliographique
Résumé
Importance: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by severe pruritus and nodule formation, significantly affecting patients' quality of life. There is an unmet need for effective therapies to address both symptoms and disease progression. Objective: To evaluate the efficacy, safety, tolerability, and pharmacokinetics of monthly dosed vixarelimab in participants with moderate to severe PN. Design, Setting, and Participants: This double-blind (DB), placebo-controlled, phase 2b randomized clinical trial was conducted from December 1, 2020, to August 24, 2023, across 72 centers in the US, Canada, Europe, and Asia. The study included male and female participants aged 18 to 80 years with physician-diagnosed PN of at least 6 months' duration and moderate to severe pruritus. Data were analyzed from October 2023 to March 2024. Interventions: Participants were randomized into 4 arms during the 16-week DB period: vixarelimab, 540 mg (high-dose group); vixarelimab, 360 mg (mid-dose group); vixarelimab, 120 mg (low-dose group); or placebo. Vixarelimab and placebo were administered subcutaneously every 4 weeks. During the 36-week open-label extension, all participants received vixarelimab, 360 mg, every 2 weeks. Main Outcomes and Measures: Key outcomes included percentage change from baseline in the Worst Itch Numeric Rating Scale (WI-NRS) at week 16, the proportion of participants achieving at least a 4-point reduction in WI-NRS at week 16, and the proportion achieving scores of 0 or 1 in the PN Investigator Global Assessment at week 16. Results: Of 190 randomized participants, 189 received 1 or more doses of the study drug (141 vixarelimab, 48 placebo). A total of 114 (60.3%) were female, 75 (39.7%) were male, and the mean (SD) age was 55.4 (13.8) years. There were 47 participants in the high-dose vixarelimab group, 47 in the mid-dose group, 47 in the low-dose group, and 48 in the placebo group. Vixarelimab significantly reduced mean (SE) WI-NRS scores at week 16 compared with placebo across all doses (vixarelimab at high-dose, mid-dose, and low-dose levels: -56.2% [4.84], -51.0% [4.83], and -33.0% [4.86], respectively; placebo, -14.5% [4.76]). Clinically meaningful 4-point or greater reductions in WI-NRS were achieved by 31 (66.0%), 29 (61.7%), and 14 (29.8%) in the high-dose, mid-dose, and low-dose vixarelimab groups, respectively, compared with 8 (16.7%) in the placebo group. PN Investigator Global Assessment scores of 0 or 1 were also higher in vixarelimab groups (high-dose group, 18 [38.3%]; mid-dose group, 14 [29.8%]; low-dose group, 7 [14.9%]; placebo group, 5 [10.4%]). No fatal or serious drug-related treatment-emergent adverse events were reported during the study, and no serious treatment-related treatment-emergent adverse events were observed during the DB period. Conclusions and Relevance: In this phase 2b randomized clinical trial, vixarelimab demonstrated rapid, sustained, dose-dependent clinical benefits in patients with PN, with a favorable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT03816891.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».