Outcomes of Triple Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy and Nasal Polyp Recurrence in Children with Cystic Fibrosis: A Systematic Review

Abstract

Chronic rhinosinusitis with nasal polyposis is highly prevalent in children with cystic fibrosis (CF), contributing substantially to morbidity, recurrent infections, and repeated surgical intervention. Although triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has demonstrated marked pulmonary benefits, its short-term to midterm effects on pediatric sinonasal disease and nasal polyp recurrence remain incompletely characterized. To systematically evaluate the impact of triple CFTR modulator therapy on nasal polyp prevalence, recurrence, and sinonasal outcomes in children with CF. This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and structured using the Population, Intervention, Comparison, Outcome, and Study Design (PICOS) framework. A comprehensive literature search was conducted in PubMed, Web of Science, ScienceDirect, and Google Scholar from database inception through 24 August 2025. Eligible studies included randomized controlled trials and observational studies evaluating pediatric patients treated with elexacaftor/tezacaftor/ivacaftor or equivalent triple CFTR modulators. Primary outcomes were nasal polyp prevalence and recurrence. Secondary outcomes included sinonasal symptom burden, radiologic findings, pulmonary function (forced expiratory volume in 1 s [FEV1]), quality of life, and safety. Risk of bias was assessed using validated methodological tools appropriate to the study design. A total of 1539 records were identified, and 14 studies met the inclusion criteria. Across studies, triple CFTR modulator therapy was consistently associated with improvement in sinonasal symptoms and radiologic sinus opacification, along with reductions in endoscopic nasal polyp burden. Pulmonary outcomes, including FEV1, also improved. Follow-up durations extended to 12 months or longer in several cohorts. Data specifically addressing polyp recurrence were limited but suggested a lower recurrence burden compared with premodulator historical cohorts. Treatment was generally well tolerated, with low discontinuation rates and no reported mortality in the included studies. Triple CFTR modulator therapy is associated with clinically meaningful improvement in pediatric sinonasal disease and may reduce nasal polyp burden in children with CF. However, evidence regarding long-term recurrence remains limited and heterogeneous. Therefore, prospective controlled studies with standardized sinonasal endpoints are needed to define the durability of response and true recurrence rates.