Dupilumab Reduces Lesion Burden in Patients with PN

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Prurigo nodularis (PN) poses significant challenges in management, particularly in patients unresponsive to topical therapies. Recent evidence from 2 large-scale phase 3 trials presented at the Society of Dermatology Physician Associates 22nd Annual Fall Dermatology Conference highlight the efficacy of dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha, in reducing lesion burden and improving outcomes for PN patients.^1-2

“Overall, the number of lesions were numerically reduced in dupilumab-treated patients vs placebo, with >70% of the dupilumab-treated patients achieving >50% healed lesions vs less than 40% in the placebo arm over 24 weeks,” researchers wrote. “These results show that PN is a heterogenous disease, and all types of lesions should be considered when monitoring patients with PN.”

Study Overview

The LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) trials evaluated dupilumab in adults with PN characterized by ≥20 nodules and severe pruritus. The 24-week randomized, double-blind, placebo-controlled studies enrolled patients inadequately controlled with or unsuited for topical therapies. Researchers reported participants received 300 mg dupilumab subcutaneously every 2 weeks following a 600 mg loading dose or matched placebo. Efficacy was assessed using the Prurigo Activity and Severity (PAS) score, alongside a detailed analysis of lesion types and healing proportions.

Key Findings

The studies found that dupilumab demonstrated robust efficacy in reducing lesion burden across diverse types in patients with PN. By week 24, the proportion of patients with more than 100 lesions dropped significantly from 34.0% to 5.2% in the dupilumab group, compared to 33.5% to 19.0% in the placebo group. The average lesion count in a representative area also showed a marked reduction, decreasing from 26.3 to 8.8 in the dupilumab group, versus 25.8 to 19.9 with placebo. Additionally, 26.1% of dupilumab-treated patients achieved complete lesion resolution compared to 7.6% in the placebo group, and 73.8% achieved ≥50% healed lesions versus 36.1% in the placebo arm. Importantly, researchers stated reductions were observed across all lesion types, with nodular lesions, characteristic of PN, decreasing substantially (78.4% to 49.7% with dupilumab vs. 75.3% to 41.1% with placebo). While papular lesions showed slight increases in both groups, ulcerated lesions nearly resolved in the dupilumab cohort, falling from 3.9% to 0.7%. These findings establish dupilumab as an effective treatment for reducing lesion burden and promoting healing in PN.

Safety Profile

The studies found that dupilumab maintained a safety profile consistent with previous studies, with no new safety concerns. This reinforces its suitability as a targeted therapy for PN, particularly in patients with high lesion burdens and unmanageable pruritus.

Clinical Implications

These findings underscore dupilumab’s efficacy in addressing the heterogeneity of PN lesions, achieving significant reductions in lesion count and pruritic burden. For clinicians, this research supports incorporating dupilumab as a first-line systemic therapy for PN, particularly in refractory cases. Importantly, the study highlights the need to consider all lesion types when monitoring disease progression and response to therapy.

Researchers found that dupilumab represents a promising advancement in the management of PN, offering durable improvements and a favorable safety profile over 24 weeks. They suggested that further studies may explore its long-term impact and effects on patient quality of life.

References

1. 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
2. Ständer S, Yosipovitch G, Kim B, et al. Dupilumab improves skin lesions of varying clinical morphologies in adult patients with prurigo nodularis. Presented at the Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference 2024. Las Vegas, Nevada. November 13–17, 2024