Predictive biomarkers of biologic therapy response in chronic rhinosinusitis with nasal polyps: a systematic review

Biologic therapies have transformed management of severe chronic rhinosinusitis with nasal polyps (CRSwNP), but response variability persists. Baseline biomarkers may identify patients most likely to benefit, yet no marker is validated for routine clinical use. This systematic review evaluated baseline biomarkers predicting clinical and endoscopic response to biologic therapy in adults with CRSwNP.

A systematic search identified studies reporting baseline biomarkers and response to biologics (dupilumab, omalizumab, anti-IL-5 agents) in adult CRSwNP. Ten studies with 489 participants met inclusion criteria. Data extraction included biomarker type, thresholds, outcomes [SNOT-22, nasal polyp score (NPS), radiologic scores], and follow-up duration. Random-effects meta-analysis was performed for dichotomized high vs. low baseline eosinophil counts. Certainty of evidence was assessed using GRADE.

Meta-analysis demonstrated that elevated eosinophils (>300 cells/µL or study-defined high) increased odds of SNOT-22 improvement (OR 3.07, 95% CI 2.00-4.72, p < 0.00001, I ² = 0%) and ≥1-point NPS reduction (OR 2.83, 95% CI 1.86-4.30, p < 0.00001, I ² = 0%). Serum IgE and other biomarkers (ECP, cytokine panels, radiologic markers) showed inconsistent associations with response across studies. Certainty of evidence was low to very low due to observational designs, heterogeneity, and imprecision. Funnel plot symmetry and Egger's test (p = 0.36) suggested minimal publication bias.

Current evidence, though limited by low certainty, suggests baseline peripheral eosinophil count is the most consistent predictor of biologic response in CRSwNP. These findings support further investigation of eosinophils as a potential predictive biomarker, but prospective validation is needed before clinical implementation. Other biomarkers showed inconsistent predictive value across studies.

PROSPERO CRD420251251904.