Featured Student: Zoya Siddiqui

Zoya Siddiqui is a fifth-year medical student in the B.A./M.D. program at the University of Missouri-Kansas City. She enjoys rollerblading, playing tennis, and exploring local coffee shops. Her research interests include inflammatory skin conditions and health disparities in dermatologic care. Writing this research summary has helped her develop a deeper appreciation for study design and its role in translating clinical evidence into patient-centered treatment decisions.

Introduction

Prurigo nodularis (PN) is a chronic, intensely pruritic skin condition characterized by multiple hyperkeratotic nodules that significantly impair patients’ quality of life. The pathogenesis involves neuroimmune dysregulation, and until recently, treatment options have been limited and often ineffective. A phase 3 trial published in JAMA Dermatology in September 2022 by Dr. Gil Yosipovitch and colleagues investigated the safety and efficacy of dupilumab, an IL-4Rα inhibitor, in managing moderate-to-severe PN.

Methodology

This multicenter, double-blind, placebo-controlled trial enrolled 151 adults with moderate-to-severe prurigo nodularis from diverse racial and ethnic backgrounds. Participants were randomized to receive either weekly subcutaneous dupilumab (300 mg following a 600 mg loading dose) or placebo for 24 weeks. The primary endpoint was the proportion of patients achieving a ≥4-point reduction on the Worst Itch Numeric Rating Scale (WI-NRS)—a patient-reported scale from 0 to 10 measuring itch severity—by week 12. Key secondary endpoints included reduction in lesion count, sleep disturbance improvement, and changes in Dermatology Life Quality Index (DLQI) scores, a validated 10-question survey measuring the impact of skin disease on quality of life.

Findings

The study demonstrated that 60% of patients in the dupilumab group achieved the primary endpoint, compared to 18% in the placebo group (p < 0.001). Dupilumab also significantly reduced lesion burden and improved patient-reported outcomes such as sleep quality and overall dermatologic quality of life. The medication was well-tolerated, with conjunctivitis being the most frequently reported adverse event, consistent with previous dupilumab studies.

Strengths and Weaknesses

One notable strength of this study is its well-structured design. By using a randomized, double-blind, placebo-controlled approach conducted across multiple centers, the investigators minimized bias and enhanced both the reliability and generalizability of the findings. The use of validated outcome measures such as WI-NRS, lesion counts, and DLQI provides meaningful insight into both clinical and patient-reported outcomes. Another notable strength is the inclusion of a racially and ethnically diverse patient population, which improves the applicability of the results to real-world settings. However, the study has several limitations, including its 24-week duration, which may not adequately capture long-term safety, durability of response, or the risk of disease recurrence after treatment discontinuation. Patients with mild disease were excluded, which limits the ability to generalize these findings to all individuals with PN. Additionally, while the study establishes dupilumab’s efficacy, it does not provide guidance on optimal treatment duration or how to manage partial responders. Cost and access to biologic therapy, which are highly relevant to clinical implementation, were also not addressed.

Applications to Future Practice

This study provides encouraging evidence for the use of dupilumab in treating prurigo nodularis, a condition with limited systemic treatment options. Dupilumab offers a well-tolerated and clinically meaningful option for patients with moderate-to-severe disease, and its success in this trial may signal a broader shift toward the use of targeted biologics in chronic pruritic disorders. Further research will be important to clarify long-term outcomes, real-world effectiveness, and strategies to improve accessibility for patients who could benefit from this treatment.