Emerging Therapies in the Treatment of Prurigo Nodularis: Biological Therapy and Systematic Review of Literature.

Abstract

Introduction: Prurigo nodularis (PN) is a chronic, intensely pruritic dermatosis characterized by hyperkeratotic nodules and a persistent itch-scratch cycle. Recent insights highlight the role of T helper type 2 cell (Th2)-driven immune dysregulation and neuroinflammation, with cytokines such as interleukin (IL)-4, IL-13, and IL-31 implicated in disease pathogenesis. PN is associated with significant morbidity and multiple comorbidities, and conventional therapies often yield suboptimal outcomes, underscoring the need for targeted treatments.

Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies published from January 2020 to March 2025 on PN pathogenesis and treatment. Search terms included combinations of "prurigo nodularis," "biologic therapy," "JAK inhibitors," "IL-4," "IL-13," and "targeted therapy." Of 123 articles screened, 26 were selected on the basis of inclusion criteria prioritizing biologics, JAK inhibitors, randomized controlled trials, cohort studies, and real-world evidence.

Results: Advances in understanding the neuroimmune basis of PN have led to the development of novel therapies. Dupilumab, targeting IL-4Rα, demonstrated significant reductions in pruritus and lesion burden in phase III trials (PRIME/PRIME2) and is approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Nemolizumab, an IL-31RA antagonist, received EMA approval in 2025 and shows rapid and sustained efficacy. Other promising agents include JAK inhibitors, vixarelimab (dual IL-31/oncostatin M (OSM) blockade), rocatinlimab (anti-OX40), and anti-IgE therapy with omalizumab. Biomarker-driven endotyping (e.g., eosinophilia, race-specific cytokine profiles) may refine patient selection.

Discussion: Biologics and JAK inhibitors represent a paradigm shift in PN management, offering durable relief through immune and neurogenic modulation. Dupilumab and nemolizumab emerge as first-line therapies with favorable safety profiles, while JAK inhibitors provide rapid relief for refractory cases. The heterogeneity of PN underscores the importance of personalized treatment approaches based on immunologic profiling.

Conclusion: Targeted therapies are revolutionizing PN treatment. Integrating clinical efficacy, immunologic endotyping, and real-world data will be pivotal to optimizing therapeutic strategies, enhancing outcomes, and personalizing care in prurigo nodularis.