Introduction <p>Prurigo nodularis (PN) is a dermatological condition characterized by intensely itchy nodules. The Prurigo Activity and Severity (PAS) assessment tool is a clinician-reported questionnaire used in the phase 3 dupilumab trials.</p> Methods <p>This post hoc analysis of pooled data from the PRIME (NCT04183335) and PRIME2 (NCT04202679) phase 3 clinical trials evaluated the effect of dupilumab on PAS score using a scoring algorithm based on items 2 (number of pruriginous lesions), 5a (percentage of pruriginous lesions with excoriations/crusts), and 5b (percentage of healed lesions). The mean change from baseline in PAS score (range: 0–11, with higher scores indicating greater severity) and the responder rates based on a clinically meaningful threshold (3.0 points) were compared between groups at week 24. The proportion of patients achieving ≤ 25% lesions with excoriations/crusts (PAS 5a) and the proportion of patients with ≥ 75% healed lesions (PAS 5b) were also analyzed to put the responder analyses in perspective.</p> Results <p>Dupilumab showed significantly greater reduction versus placebo in mean change in PAS score from baseline to week 24 (absolute least squares [LS] mean difference: –2.7, 95% confidence interval [CI] [–3.3, –2.1]; <i>P</i> &lt; 0.0001). PAS responder rate was significantly higher with dupilumab versus placebo (69.3% versus 27.2%, <i>P</i> &lt; 0.0001). At week 24, significantly higher proportions of dupilumab-treated patients compared with placebo achieved both ≤ 25% lesions with excoriations/crusts (PAS 5a; 71.2% versus 30.4%; odds ratio [OR]: 6.2 [3.6, 10.8], <i>P</i> &lt; 0.0001) and ≥ 75% healed lesions (PAS 5b; 56.2% versus 18.4%; OR: 5.9 [3.3, 10.4], <i>P</i> &lt; 0.0001).</p> Conclusions <p>This evidence shows that the effect of dupilumab on PAS score is significant and clinically meaningful to patients.</p> <p>Trial registration: ClinicalTrials. gov identifier; PRIME NCT04183335, PRIME2 NCT04202679.</p>