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IntroductionCystic fibrosis (CF) is a severe genetic disorder caused by pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to multisystem complications including chronic rhinosinusitis and nasal polyposis. Recent advances in CFTR modulator therapies have revolutionized systemic disease control, but their impact on sinonasal disease remains less explored.MethodsA systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42025632498). Searches were performed across PubMed/MEDLINE, Cochrane Library, and Embase through March 2025. Studies reporting nasal endoscopic outcomes using validated scoring systems before and after CFTR modulator therapy were included.ResultsOut of 232 identified records, 10 studies met inclusion criteria, representing populations from six countries. Most studies assessed triple therapy (Elexacaftor/Tezacaftor/Ivacaftor). Endoscopic scores, including the Modified Lund-Kennedy scale, showed significant reductions in nasal polyps, mucosal edema, and discharge. Pediatric and adult groups benefited alike, with triple therapy proving more effective than dual or monotherapy. Secondary outcomes included improved pulmonary function, weight gain, and olfactory recovery.ConclusionThis review demonstrates that CFTR modulators provide significant benefits for sinonasal disease in CF, reinforcing their role as a comprehensive therapeutic approach addressing both upper airway and systemic disease burdens.

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BackgroundThe development of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (correctors and potentiators) emerged as a promising approach, aiming to restore CFTR protein function. A lack of head-to-head trials comparing CFTR modulators leaves uncertainty about the optimal treatment. We aimed to evaluate the comparative efficacy and safety of CFTR modulators for people with cystic fibrosis who have a phe508del mutation.MethodsWe conducted an extensive literature search for both published and unpublished randomized controlled trials in databases such as PubMed, EMBASE, Scopus, Ovid, Cochrane Central Register of Controlled Trials, and international trial registers from inception until May 21, 2025. We included studies that used any CFTR modulators (monotherapy or combination) for the treatment of children and adults with a confirmed diagnosis of cystic fibrosis with phe508del CFTR mutation. Two reviewers independently and in duplicate performed study selection, data extraction, and quality assessment. Our primary outcomes were efficacy (change in percent predicted forced expiratory volume (ppFEV1), sweat chloride) and safety (frequency of serious adverse events). We performed a random effect bayesian network meta-analysis for each outcome using the gemtc and BUGSnet package in R. The confidence in the network meta-analysis framework was utilized to determine the certainty of evidence. The study protocol was registered with Prospective Register of Systematic Reviews (CRD42024505081).FindingsOf the 3473 studies identified through our literature search, 29 studies involving 6450 patients examining 34 treatment combinations were included. For adults treated over 4-8 weeks, vanzacaftor 10 mg-tezacaftor 100 mg-deutivacaftor 150 mg combination therapy had a significant improvement over placebo in improving ppFEV1 (MD: 15.9; 95% CrI: 7.2-24.2 [high certainty]) with a SUCRA of 92% suggesting the highest probability of effectiveness. Moreover, the vanzacaftor 20 mg-tezacaftor 100 mg-deutivacaftor 150 mg showed a significant reduction in sweat chloride levels (MD: -49.3 mmol/L; 95% CrI: -67.2 to -31.7 [high certainty]) and improved the CFQ-R scores (MD: 39; 95% CrI: 21.2-56.9; [high certainty]) when compared to placebo after 4-8 weeks of treatment. Our findings also highlighted that the triple combination therapies of vanzacaftor 20 mg-tezacaftor 100 mg-deutivacaftor 250 mg and elexacaftor 200 mg-tezacaftor 100 mg-ivacaftor 150 mg provided clinically meaningful improvements across all measured outcomes in adults treated for more than 8 weeks. Confidence in the estimates ranged from high to low, and safety analyses were limited by the low serious adverse event rates.InterpretationOur findings indicate that vanzacaftor-tezacaftor-deutivacaftor and elexacaftor-tezacaftor-deutivacaftor emerged as the most effective treatment options in adults. However, these results should be interpreted cautiously due to limited data and the low quality of existing evidence.FundingNone.

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Objective: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of elexacaftor–tezacaftor–ivacaftor (ELX-TEZ-IVA) on patients with cystic fibrosis (CF). Methods: A systematic search was performed in PubMed, Embase, and the Cochrane Library from inception to August 1, 2022. Meta-analysis was conducted using Review Manager 5.3 software. Results: Six studies comprising seven reports involving a total of 1125 CF patients were included. The meta-analyses indicated that ELX-TEZ-IVA significantly improved the percentage predicted forced expiratory volume in 1 s (ppFEV1) by 10.29% (95% confidence interval (CI) (6.44, 14.14), p  < 0.00001) and the CF questionnaire-revised respiratory domain (CFQ-R RD) by 14.59 points (95% CI (9.25, 19.94), p  < 0.00001) compared to placebo, ivacaftor (IVA), or tezacaftor–ivacaftor (TEZ-IVA). In addition, the ELX-TEZ-IVA group showed significantly lower sweat chloride concentrations by 40.30 mmol/L (95% CI (−49.85, −30.74), p  < 0.00001). However, the incidence of adverse events in the ELX-TEZ-IVA group was slightly higher than that in the placebo, IVA, or TEZ-IVA groups. Conclusion: ELX-TEZ-IVA demonstrated efficacy in improving ppFEV1, CFQ-R RD, and sweat chloride concentrations in patients with CF. However, caution should be exercised regarding the incidence of AEs, particularly mild and moderate ones

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