Johns Hopkins Medical Institutions, Baltimore, Maryland.
University of Miami, Miami.
JAMA Dermatol. 2024 Aug 1;160(8):813-821. doi: 10.1001/jamadermatol.2024.1634.
Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN.
To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN.
DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2.
Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks.
WI-NRS score at specified time points up to 24 weeks after randomization.
A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods.
This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN.
NCT04183335 (PRIME) and NCT04202679 (PRIME2).
结节性痒疹（PN）是一种使人虚弱的皮肤病，其特征是标志性症状为慢性瘙痒；使用最严重瘙痒数字评定量表（WI-NRS）评估 PN 的瘙痒强度，以评估 2 项最近关于度普利尤单抗治疗 PN 的 3 期研究的主要疗效终点。
验证 WI-NRS 的心理测量特性，并确定中重度 PN 患者的临床有意义的改善阈值。
设计、设置和参与者：在 PRIME 和 PRIME2 试验的这项二次分析中，通过深入的患者访谈评估 WI-NRS 的内容有效性。使用来自随机、双盲和安慰剂对照研究的中重度 PN 患者的盲法、意向治疗（ITT）数据进行心理测量评估。心理测量评估包括重测信度、结构效度、已知群体效度以及对中重度 PN 成年患者的变化敏感性。使用基于锚定和分布的方法确定 WI-NRS 评分中患者有意义的内在改善阈值。在每项研究完成后进行数据分析，PRIME 的数据分析时间为 2019 年 12 月至 2021 年 11 月，PRIME2 的数据分析时间为 2020 年 1 月至 2021 年 8 月。
度普利尤单抗（300mg）或安慰剂每 2 周皮下注射一次，共 24 周。
随机分组后 24 周内指定时间点的 WI-NRS 评分。
在这两项研究中，共有 20 名患者（平均[标准差]年龄，49.3[17.2]岁；11 名女性[55%]）纳入研究；在汇总的 ITT 分析中，共有 311 名患者（平均[标准差]年龄，49.5[16.1]岁；203 名女性[65.3%]）。WI-NRS 问题（20 名患者中的 20 名）、回忆期（20 名患者中的 19 名）和反应量表（20 名患者中的 20 名）对于 PN 患者来说易于理解且相关。在筛查和基线之间观察到了足够的重测信度（组内相关系数=0.72，使用患者总体印象严重程度[PGIS]来定义稳定患者）。与其他概念上相关的测量指标呈中度至强相关性（绝对 r 值范围为 0.34-0.73），与不太相关的测量指标呈较弱相关性（绝对 r 值范围为 0.06-0.32），支持了收敛和判别效度。WI-NRS 具有变化敏感性，这一点可通过不同组之间从基线的变化差异（根据 PGIS 变化和变化后的患者总体印象[PGIC]）得到证明。使用基于锚定的方法（PGIS 和 PGIC），临床有意义的改善阈值为 4 分（范围，3.0-4.5），这也得到了基于分布的方法的支持。
本研究发现，WI-NRS 可能是一种合适的工具，可用于支持评估成人 PN 瘙痒强度的疗效终点。
NCT04183335（PRIME）和 NCT04202679（PRIME2）。
