Prurigo nodularis (PN) is a chronic inflammatory skin disease with intensely pruritic nodules. The LIBERTY-PN PRIME and PRIME2 phase 3 trials enrolled adults with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. Patients were randomized 1:1 to 300 mg dupilumab or placebo subcutaneously every 2 weeks for 24 weeks. The primary endpoint was pruritus improvement, measured by proportion of patients with a ≥4-point reduction in Worst Itch Numeric Rating Scale (WI-NRS) from baseline at week 24 (PRIME) or week 12 (PRIME2). Key secondary endpoints included nodule number reduction to ≤5 at week 24. PRIME and PRIME2 enrolled 151 and 160 patients, respectively. Both trials met all the pre-specified primary and key secondary endpoints. A ≥4-point WI-NRS reduction at week 24 in the dupilumab and placebo arms was achieved by 60.0% and 18.4% of patients, respectively, in PRIME (95% confidence interval (CI), 27.8–57.7 for the difference, P < 0.001) and at week 12 by 37.2% and 22.0% of patients, respectively, in PRIME2 (95% CI, 2.3–31.2; P = 0.022). Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions versus placebo in PN. Safety was consistent with the known dupilumab safety profile.

ClinicalTrials.gov identifiers: NCT04183335 and NCT04202679.

结节性痒疹 (PN) 是一种慢性炎症性皮肤病，伴有强烈的瘙痒性结节。LIBERTY-PN PRIME 和 PRIME2 3 期试验纳入了患有 PN 的成年人，其中结节数≥20 个，且局部治疗无法控制严重瘙痒。Dupilumab 是一种全人源单克隆抗体，可阻断白细胞介素 (IL)-4 和 IL-13 的共享受体成分。患者以 1:1 的比例随机分配至 300 mg dupilumab 或安慰剂，每 2 周皮下注射一次，持续 24 周。主要终点是瘙痒改善，衡量标准是在第 24 周（PRIME）或第 12 周（PRIME2）时最严重瘙痒数值评定量表（WI-NRS）较基线降低 ≥ 4 分的患者比例。关键的次要终点包括第 24 周时结节数量减少至≤5 个。PRIME 和 PRIME2 分别招募了 151 名和 160 名患者。两项试验均达到了所有预先指定的主要和关键次要终点。在第 24 周，dupilumab 组和安慰剂组分别有 60.0% 和 18.4% 的患者在 PRIME 中实现 WI-NRS ≥ 4 点降低（95% 置信区间 (CI)，差异为 27.8–57.7，P  < 0.001）和第 12 周时分别​​有 37.2% 和 22.0% 的患者出现 PRIME2（95% CI，2.3–31.2；P  = 0.022）。在 PN 中，与安慰剂相比，Dupilumab 在瘙痒和皮肤损伤方面表现出具有临床意义和统计学意义的改善。安全性与已知的 dupilumab 安全性一致。

ClinicalTrials.gov 标识符：NCT04183335 和 NCT04202679。