Cystic fibrosis triple therapy improves lung ventilation, morphology in children

Key takeaways:

• Lung clearance index improved in month 3 and 12 of elexacaftor/tezacaftor/ivacaftor therapy.
• Both genotype groups had a significantly lower MRI global score and MRI morphology score from baseline to 3 months.

Lung clearance index and MRI scores improved in kids aged 6 to 11 years with cystic fibrosis and at least one F508del allele receiving elexacaftor/tezacaftor/ivacaftor therapy, according to results published in European Respiratory Journal.

“Triple combination therapy significantly reduced the severity of lung disease in young patients and, at least during the 1-year study period, also prevented the disease from progressing,” Marcus A. Mall, MD, director of the department of pediatric respiratory medicine, immunology and critical care medicine at Charité – Universitätsmedizin Berlin, said in a press release. “The majority of the children even achieved normal lung function with the triple combination therapy. That’s a highly positive result!”

In a prospective, observational, multicenter study, Mall and colleagues evaluated 107 children aged 6 to 11 years with CF heterozygous for F508del and a minimal function mutation (F/MF genotypes; n = 40; mean age, 9.3 years; 47.5% female) or homozygous for F508del (F/F genotype; n = 67; mean age, 8.1 years; 52.5% female) treated with elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta, Vertex Pharmaceuticals) to determine how the triple therapy impacts lung clearance index (LCI, a sensitive lung function test) at 12 months and the lung MRI score at 3 months.

As Healio previously reported, in children aged 6 years and older with CF and either F/MF genotypes or F/F genotypes, ETI was safe and well tolerated for up to 120 weeks.

Most of the F/F genotype group had previously received either lumacaftor/ivacaftor (n = 58) or tezacaftor/ivacaftor (n = 5). In the F/MF genotype group, no patients had previously received a CFTR modulator treatment.

By the third month of ETI therapy, sweat chloride concentration and percent-predicted FEV₁ improved in both genotype groups and had a “stable course in spirometry thereafter,” according to researchers.

Between baseline and the 3-month mark, researchers found reductions in median LCI via multiple-breath washout data in both the group with F/MF genotypes (7.3 to 6.6 unit) and the group with F/F genotypes (7.1 to 6.5 unit). This change signaled improvement and a normal range LCI.

At month 12 of triple therapy, median LCI was further lowered among children with F/MF genotypes (–1 unit; interquartile range [IQR], –2 to –0.1; P < .01) and children with F/F genotypes (–0.8 units; IQR, –1.9 to –0.2; P < .001).

Researchers observed a greater proportion of children with a normal LCI at 12 months when compared with baseline in both genotype groups (F/MF, 40.5% to 86.4%; F/F, 48.5% to 66.1%).

Decreases in the MRI global score also indicated improvement, and both genotype groups had a significantly lower MRI global score from baseline to 3 months (F/MF, –4 points; IQR, –9 to 0; F/F, –3.5 points; IQR, –7.3 to –0.8).

Additionally, both the F/MF and F/F groups had significant decreases in the MRI morphology score (F/MF, –4 points; IQR, –5 to –2; F/F, –3 points; IQR, –6 to 0; both P < .001) at 3 months, whereas only the F/F group had a significantly lower MRI perfusion score (–2 points; IQR, –4 to 0; P < .001).

Within the MRI morphology score, children with F/MF genotypes had 1-point drops in the MRI mucus subscore (IQR, –4 to 1; P < .05) and the MRI wall thickening/bronchiectasis subscore (IQR, –2 to 0; P < .01), as did children with F/F genotypes (mucus subscore, –1 point; IQR, –3 to 0; wall thickening/bronchiectasis subscore, –1 point; IQR, –2 to 0; both P < .01).

Researchers noted a significant correlation between LCI changes and percent-predicted FEV₁ changes but not between LCI changes and MRI global score changes.

“We hope starting triple combination therapy in early childhood will be able to prevent the emergence of severe symptoms and the formation of structural changes in the lungs,” Mirjam Stahl, MD, head of the division of cystic fibrosis at the department of pediatric respiratory medicine, immunology and critical care medicine at Charité – Universitätsmedizin Berlin, said in the release.

Reference:

• Cystic fibrosis: School-aged children benefit from triple therapy combination. https://www.charite.de/en/service/press_reports/artikel/detail/cystic_fibrosis_school_aged_children_benefit_from_triple_combination_therapy/. Published July 10, 2024. Accessed July 15, 2024.