Psychophysical Olfactory Outcomes After Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review and Meta-Analysis.

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 new biologics emerging and real-world evidence accumulating, a comprehensive evaluation is warranted. This systematic review and meta-analysis included eight RCTs (n = 2,081) and an additional review of 20 cohorts (n = 1,681). Among RCTs, biologic therapy produced a large, pooled effect in psychophysical olfactory outcomes (standardised mean difference (SMD) = 1.00, 95% CI = 0.62–1.38, p < 0.0001). Effects differed between agents; dupilumab and tezepelumab produced the largest improvements (SMDs: 1.53, and 1.25, respectively). Omalizumab and telikibart each yielded modest, but statistically significant improvements (SMDs: 0.56, and 0.71, respectively). Mepolizumab and benralizumab did not show statistically significant effects (SMDs: 0.13, and 0.25, respectively). The cohort studies supported a large effect of dupilumab (SMD = 1.57) but focused almost exclusively on dupilumab (19 out of 20 studies). Tezepelumab and dupilumab appear most effective for smell improvement based on available evidence. Head-to-head trials are warranted to more precisely clarify comparative efficacy.