Dupilumab treatment for CRSwNP results in a 7.9% pooled proportion of post-treatment hypereosinophiliaDupilumab treatment for nasal polyps can cause high eosinophil counts

BackgroundDupilumab may cause a treatment-emergent rise in circulating eosinophils, but the frequency, temporal pattern, predictors, and clinical consequences of hypereosinophilia (HE) in chronic rhinosinusitis with nasal polyps (CRSwNP) remain incompletely defined.MethodsWe performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 systematic review and meta-analysis of PubMed/MEDLINE and Embase.com studies reporting post-treatment circulating eosinophil outcomes in dupilumab-treated CRSwNP. Potentially overlapping reports were linked at the cohort and outcome level. The primary outcome was post-treatment HE ≥1,500 cells/µL, synthesized using a binomial-normal random-effects generalized linear mixed model (GLMM) with a logit link.ResultsThe combined searches identified 368 records; after deduplication, 255 records were screened, 72 reports underwent full-text assessment, and 50 eligible reports mapped to 42 study/cohort clusters. Six independent cohorts contributed 172 HE events among 1,047 patients, yielding a pooled HE proportion of 7.9% [95% confidence interval (CI), 2.8%–20.1%; τ = 1.19]. Following outcome-specific risk-of-bias reassessment, a sensitivity analysis excluding the two high-risk cohorts retained four studies (166 events among 865 patients) and yielded 12.1% (95% CI, 3.9%–32.0%; τ = 1.06). Across seven longitudinal cohorts, study-level blood eosinophil central estimates generally increased during the first 1–6 months and subsequently declined, while transient, persistent, repeated, and late-onset HE phenotypes were reported. Higher baseline eosinophil burden was the most consistent predictor signal, but no threshold was externally validated as a clinical decision rule. Permanent eosinophilia-related treatment modification occurred in 6/548 patients and severe eosinophilic organ complications occurred in 4/576 patients. Certainty of evidence was very low across prespecified domains.ConclusionsTreatment-emergent HE during dupilumab therapy for CRSwNP most often appears to represent a pharmacodynamic laboratory phenomenon, whereas permanent treatment modification and severe eosinophilic organ complications are uncommon in the available cohorts. Clinical interpretation should consider magnitude, temporal trajectory, persistence, associated symptoms, and evidence of organ involvement; standardized longitudinal monitoring is needed to improve ascertainment and identify the rare clinically consequential phenotype, although the evidence does not define a universal monitoring schedule.