Restoring the Sense of Smell: A Systematic Review and Meta-Analysis of Biologic Therapies for Chronic Rhinosinusitis with Nasal Polyps.

PURPOSE OF REVIEW: Smell loss is among the most debilitating symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP). We aimed to synthesize current evidence on the smell-restoring efficacy of biologics, focusing on outcomes measured by psychophysical tests.

RECENT FINDINGS: Biologics mark a paradigm shift in the management of refractory CRSwNP, offering targeted, effective and safe treatment options. However, their relative impact on psychophysical smell outcomes remains uncertain. With several biologics now approved and real-world evidence emerging, a comprehensive evaluation is needed. This is a systematic review and meta-analysis of 8 RCTs (n = 2,024) and an additional review of 20 cohorts (n = 1,685). Among RCTs, biologic treatment produced a moderate to large pooled improvement in psychophysical smell scores (standardized mean difference, [SMD] = 0.72 (95% CI 0.32-1.13), p = 0.0004). The effect differed between drugs (χ² = 23.95, p < 0.0002). Dupilumab showed the largest improvements across four RCTs (SMD = 1.16, 95% CI = 0.35-1.97). In single RCTs, benralizumab showed large effect (1.03, 0.55-1.51), tezepelumab (0.56, 0.46-0.67), telikibart (0.35, 0.11-0.59), and omalizumab (0.27, 0.15-0.40) yielded modest but significant improvements. Mepolizumab showed no effect (0.1330 (95% CI -0.2490-0.5150). Blood-eosinophil level correlated with treatment response (p < 0.001). The cohort studies supported the findings (SMD = 1.20, 95% CI = 0.99-1.42), though most data were derived from studies of dupilumab. Overall, biologics substantially improve psychophysically measured olfactory function in CRSwNP. Future head-to-head trials are warranted to delineate comparative efficacy of smell recovery.