Post Hoc Analysis Shows Dupilumab Improves PAS Scores in Patients with Prurigo Nodularis

A post hoc pooled analysis of the PRIME and PRIME2 phase 3 trials further evaluated the effect of dupilumab on prurigo activity and severity in adult patients with prurigo nodularis (PN).¹ The analysis specifically focused on Prurigo Activity and Severity (PAS) score changes and clinically meaningful responder thresholds through week 24, including overall score reduction, ≤ 25% active excoriations/crusts, and ≥ 75% healed lesions.

Background

PN is a chronic, intensely pruritic dermatologic condition characterized by the presence of multiple firm, hyperkeratotic nodules that most commonly affect the extensor surfaces of the extremities and trunk. It is strongly associated with a persistent itch–scratch cycle, in which severe pruritus drives repetitive scratching that leads to skin trauma, nodule formation, and further inflammation, perpetuating disease chronicity. Although its exact pathophysiology is multifactorial, emerging evidence highlights a prominent role for type 2 inflammatory signaling, including IL-4 and IL-13 pathways, which have helped drive the development of targeted biologic therapies such as dupilumab.

Trial Design

Data were pooled from the randomized, double-blind, placebo-controlled PRIME (NCT04183335) and PRIME2 (NCT04202679) trials, including 311 adults with moderate to severe PN uncontrolled with topical therapies (dupilumab n = 153; placebo n = 158). Baseline disease burden was substantial, with mean PAS scores of 8.4 in the dupilumab arm and 8.6 in the placebo arm, on a scale ranging between 0 and 11.

The PAS scoring algorithm used here was based on an unweighted sum of 3 key items: estimated lesion number (item 2), percentage of lesions with excoriations/crusts (item 5a), and percentage of healed lesions (item 5b), which together capture both inflammatory activity and reparative response. Clinically meaningful improvement was defined a priori as a ≥3-point absolute reduction or ≥37% relative reduction in PAS score. Additional clinically interpretive thresholds included achieving ≤25% lesions with excoriations/crusts (minimal active disease) and ≥75% healed lesions (robust lesion resolution).

Results

At week 24, dupilumab demonstrated a significantly greater reduction in PAS score compared with placebo. The least squares mean difference in absolute PAS change was −2.7 (95% CI −3.3 to −2.1; P < 0.0001), with a −31.8% relative improvement versus placebo (P < 0.0001). Treatment differences emerged as early as week 4 and were sustained through week 24. Responder analyses mirrored these findings. By week 24, 69.3% of dupilumab-treated patients achieved a ≥3-point reduction in PAS compared with 27.2% of placebo-treated patients (odds ratio [OR] 7.1; P < 0.0001). Similarly, 67.3% achieved a ≥37% relative improvement versus 23.4% with placebo (OR 8.2; P < 0.0001).

Improvements in individual PAS components further contextualized these global score reductions. For PAS item 5a (percentage of pruriginous lesions with excoriations or crusts), dupilumab significantly reduced active inflammatory lesion burden at all time points. At week 24, 71.2% of dupilumab-treated patients achieved ≤25% lesions with excoriations/crusts compared with 30.4% of placebo-treated patients (OR 6.2; P < 0.0001). This reflects meaningful suppression of the itch–scratch cycle and reduction in ongoing skin damage. Conversely, PAS item 5b (percentage of healed lesions) demonstrated robust gains in tissue recovery. By week 24, 56.2% of dupilumab-treated patients achieved ≥75% healed lesions versus 18.4% of placebo patients (OR 5.9; P < 0.0001). Improvements in healing were also evident as early as week 4 and increased progressively through week 24.

Conclusion

As previously reported in the parent trials, dupilumab demonstrated a favorable tolerability profile, with nasopharyngitis and headache among the most common adverse events, and no new safety signals identified.² Limitations of this analysis include its post hoc design, the relatively short 24-week duration, and the controlled clinical trial population, which may not fully represent real-world heterogeneity in PN. Nonetheless, these findings emphasize that dupilumab exerts a dual therapeutic effect in PN, reducing active lesion inflammation and simultaneously promoting lesion healing.

References

1. Stander S, Zeidler C, Msihid J, et al. Dupilumab Improves Prurigo Activity and Severity in Patients with Prurigo Nodularis: A Post Hoc Analysis of Pooled Results from the PRIME and PRIME2 Trials. Dermatol Ther (Heidelb). Published online April 1, 2026. doi:10.1007/s13555-026-01692-3

2. Yosipovitch G, Mollanazar N, Ständer S, et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med. 2023;29(5):1180-1190. doi:10.1038/s41591-023-02320-9