On 19 May, at the 2025 American Thoracic Society (ATS) International Conference, researchers from Cincinnati Children’s Hospital presented compelling evidence that functional improvement in paediatric cystic fibrosis (CF) patients receiving elexacaftor/tezacaftor/ivacaftor (ETI) therapy is driven by regional clearance of mucus plugs. Using advanced imaging techniques—ultrashort echo-time (UTE) magnetic resonance imaging (MRI) and hyperpolarised xenon-129 (¹²⁹Xe) ventilation MRI—the study offered a granular view of structural and functional lung changes, offering insight into why certain patients derive greater clinical benefit from cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy.
The prospective study enrolled 30 paediatric CF patients who underwent imaging and spirometry both before and following the initiation of CFTR modulator therapy. A total of 19 patients received ETI while 11 were started on lumacaftor/ivacaftor (LI). Each lung lobe was scored for structural abnormalities, including mucus plugging, bronchiectasis, wall thickening, and opacities. Functional outcomes were assessed via ventilation defect percentage (VDP) and percent predicted FEV₁ (ppFEV₁).
Go deeper with GlobalData
ETI-treated patients demonstrated significant clinical and structural improvement across multiple domains. VDP improved by a mean of 6±6% (p<0.001), while ppFEV₁ increased by 9±12% (p=0.01). These changes were tightly correlated with a decrease in mucus scores as observed via UTE MRI. Specifically, ETI patients with a 0.5-point or greater reduction in mucus burden experienced the most substantial functional gains—12±14% increase in FEV₁ and 8±4% reduction in VDP (both p<0.01). Conversely, patients on LI showed no statistically significant improvement in either imaging or functional metrics.
Other imaging markers, including consolidation, air trapping, and ground-glass opacities, improved significantly in the ETI group, while bronchiectasis and wall thickening—typically associated with irreversible airway damage—remained unchanged. In one illustrative case, a paediatric patient with the largest improvement in mucus score (−4.5) experienced a 34% rise in FEV₁ and a 14% drop in VDP, underscoring the mechanistic link between mucus clearance and restored pulmonary function.
Clinically, these findings support a more nuanced understanding of how ETI therapy improves outcomes, highlighting mucus clearance as a key driver of therapeutic efficacy rather than merely a downstream effect. The use of UTE and ¹²⁹Xe MRI, which offer high-resolution, radiation-free imaging of airway pathology and ventilation, respectively, adds a valuable dimension to conventional spirometry and could play a growing role in stratifying treatment response in both clinical trials and real-world practice.
This data reinforces ETI’s dominant profile, particularly in the paediatric setting, where long-term structural preservation is critical. The ability to directly correlate mucus plug resolution with improvements in FEV₁ and VDP adds scientific credibility to ETI’s clinical value and may inform payer decision-making by providing objective, imaging-based endpoints.
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataWith Vertex’s ETI franchise continuing to set the standard, these findings raise the bar for emerging competitors in the CFTR modulator space. Future entrants, whether oral, inhaled, or gene-editing-based, will be expected not only to match ETI’s functional benefits but to demonstrate similar or superior regional lung clearance and structural remodelling. The integration of advanced imaging into clinical development pipelines may prove critical for differentiation, particularly as value-based care models demand measurable outcomes tied to cost-effectiveness.
Key opinion leaders interviewed by GlobalData have emphasised that non-invasive, radiation-free imaging tools such as UTE and Xe MRI will be instrumental in guiding therapy in the next era of CF care. Their use may enhance treatment personalisation and enable more precise forecasting of long-term benefit, critical factors in an increasingly competitive and outcomes-driven market.
