Abstract
Prurigo nodularis (PN) is a chronic dermatological condition characterized by intensely pruritic nodules resulting from repeated scratching. Its pathogenesis involves neuroimmune dysregulation, inflammatory cytokines, and neural proliferation. Conventional treatments often provide limited relief, necessitating novel therapeutic approaches. This narrative review explores emerging biologics and small molecules for PN treatment, assessing their mechanisms, efficacy, and safety. A comprehensive literature search was conducted using PubMed, Google Scholar, and Web of Science for relevant studies up to February 2025. Additionally, ongoing clinical trials were identified through a verified international website. The search terms included "prurigo nodularis", "biologic treatments", "monoclonal antibodies", "small molecules", and "JAK inhibitors". Among new treatment options, dupilumab, an IL-4 receptor antagonist, and nemolizumab, an IL-31 receptor inhibitor, demonstrated significant efficacy in reducing pruritus and lesion severity in PN patients. Other promising monoclonal antibodies include vixarelimab (OSMRβ inhibitor) and barzolvolimab (KIT inhibitor). Small molecules such as JAK inhibitors (upadacitinib, povorcitinib) also show potential by modulating inflammatory pathways. Clinical trials highlight their efficacy, safety, and long-term benefits. Emerging biologics and small molecules represent a transformative approach for PN management, offering targeted therapies that address underlying immunological and neurological mechanisms. Ongoing research and long-term studies are crucial to optimizing treatment strategies and improving patient outcomes.