512 - Dupilumab treatment improves satisfaction in patients with prurigo nodularis who did not achieve the multicomponent endpoint: analysis from LIBERTY-PN PRIME and PRIME2
Authors: Kwatra Shawn G , Yosipovitch Gil , Ständer Sonja , Mendes-Bastos Pedro , Tsai Tsen-Fang , Kim Brian S , Praestgaard Amy , Bansal Ashish , Makhija Melanie , Bahloul Donia , Thomas Ryan B , Zahn Joseph , Wiggins Simmi 
Published: February 2024

Abstract

Introduction
Patients with prurigo nodularis (PN) often report high disease burden with substantial impact on quality of life. Patient Global Impression of Change (PGIC) and Severity (PGIS) are patient self-assessment measures that quantify their experience of disease during treatment. Dupilumab has recently been approved as the first systemic treatment for PN in the US and Europe.

Objectives
To evaluate patient-reported global impression of disease severity improvement in dupilumab-treated patients with PN during the LIBERTY-PN PRIME and PRIME 2 trials.

Materials & Methods
PRIME and PRIME2 were randomized, double-blind, multicenter, parallel-group, 24-week, phase 3 trials in adults with PN with ≥20 nodules and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks. In this analysis, data from the two studies were pooled. Patient satisfaction was assessed in the overall placebo group, overall dupilumab-treated group, and those treated with dupilumab who did not achieve the stringent multicomponent endpoint (n = 99) of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0–10) and an Investigator’s Global Assessment PN Stage (IGA PN-S, score range: 0–4) score 0 or 1 (clear or almost clear; ≤5 nodules) at Week (W) 24. Endpoints include proportion of patients achieving: PGIC (range: 0–6) scores of 0 or 1 (very much better or moderately better) at W12, and W24; and PGIS (range: 1–4) score of 1 or 2 (none or mild) at baseline, W12, and W24. Safety was also assessed.

Results
Baseline demographic and clinical characteristics were generally similar between groups. In the overall dupilumab and placebo groups, baseline mean (SD) WI-NRS scores were 8.6 (0.9) and 8.4 (1.1), respectively; 32.7% and 34.2% had an IGA PN-S score of 4 (remaining patients had IGA PN-S 3); and mean (SD) PGIS scores were 3.7 (0.5) and 3.7 (0.5) respectively. In dupilumab multicomponent endpoint non-responders, mean (SD) WI-NRS score was 8.6 (0.9). 35.4% and 64.6% had an IGA PN-S score of 4 and 3 respectively; and mean (SD) PGIS score was 3.7 (0.5). At W12, 68.0% vs 38.0% (P &lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIC 0 or 1, while 55.6% of dupilumab multicomponent non-responders achieved this endpoint (P = 0.0099 vs placebo). At W24, this increased to 74.5% vs 32.9% (P &lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieving PGIC 0 or 1, and 61.6% of multicomponent non-achievers (P &lt; 0.0001 vs placebo). At W12, 51.6% vs 22.2% (P &lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 40.4% of multicomponent non-responders achieved the endpoint (P = 0.0027 vs placebo). At W24, 61.4% vs 24.1% (P &lt; 0.0001 vs placebo) of dupilumab-treated vs placebo-receiving patients achieved PGIS 1 or 2, while 44.4% of multicomponent non-responders achieved the endpoint (P = 0.0025 vs placebo). Safety findings were consistent with the known dupilumab safety profile.

Conclusions
While not all patients achieved the stringent multicomponent endpoint within the 24-week treatment period during PRIME and PRIME 2 trials, around half of the dupilumab-treated patients still reported significantly more improvement in disease severity and satisfaction with therapy. Overall safety was consistent with the known dupilumab safety profile.