Biologics for chronic rhinosinusitis with nasal polyps: from downstream cytokine blockade to upstream epithelial targets

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogenous inflammatory disease that often persist despite optimal medical and surgical treatment. Advances in the understanding of CRS immunopathophysiology have led to the development of biologic therapies targeting specific inflammatory pathways. This review summarizes the current knowledge on the downstream biologics and the latest update on the next generation upstream biologics therapies in CRSwNP, with focus on endotype-driven treatment selection. RECENT FINDINGS: Biologic therapies targeting downstream mediators of type 2 inflammation, including immunoglobulin E and interleukins interleukin (IL)-4, IL-5 and IL-13, have demonstrated substantial clinical benefit in selected patients. Nevertheless, CRSwNP commonly involves overlapping inflammatory endotypes, which may limit treatment response. Newer biologics targeting upstream epithelial-derived cytokines offer broader approach by modulating multiple inflammatory pathways simultaneously and may address current therapeutic gaps. The development of long-acting biologics also improves treatment convenience and adherence. SUMMARY: Biologic therapy has shifted CRSwNP management towards a more personalized, mechanism-based approach. Upstream-targeted treatments represent an important step forward, particularly for patients with refractory or mixed disease. Future research should focus on biomarker-guided therapy and long-term clinical outcomes.