Vixarelimab in Patients With Prurigo Nodularis
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
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.
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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) | 0.000 | 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