Fewer pulmonary exacerbations, hospitalizations with Trikafta: Study
Among hospitalized CF children, proportion from minority groups has increased
Treatment with Trikafta (elexacaftor/tezacaftor/ivacaftor) contributed to a reduction in pulmonary exacerbations requiring hospitalization between 2018 and 2022 among children and young adults with cystic fibrosis (CF).
That’s according to a recent study in the U.S. that also demonstrated that the proportion of hospitalized CF patients from minority groups, who are less likely to be treated with CFTR modulators such as Trikafta, was higher in 2022.
“We hope these results will prompt targeted efforts to monitor these at‐risk children more closely on an outpatient basis and encourage development of novel treatment strategies to reduce severe pulmonary exacerbations and improve outcomes in children with CF,” the researchers wrote.
The study, “Changing Epidemiology of Pediatric Pulmonary Exacerbations in Cystic Fibrosis,” was published in Pediatric Pulmonology.
Hospitalizations due to pulmonary exacerbations decreased by two-thirds
CF is caused by genetic mutations that result in no or insufficient activity of the CFTR protein, leading to the accumulation of thick and sticky mucus in several organs, particularly in the lungs. Pulmonary exacerbations, characterized by a sudden decline in lung function, are frequent among people with CF, often leading to hospitalizations and the need for antibiotics.
However, the introduction of Trikafta in 2019, and its expansion to patients as young as 2 years in 2023, has contributed to a significant reduction of pulmonary exacerbations among children with CF.
To learn more, researchers reviewed data from all children and young adults with CF who were hospitalized and treated with intravenous, or into-the-vein, antibiotics for pulmonary exacerbations at five pediatric CF centers accredited by the Cystic Fibrosis Foundation. Data from 2018 and 2022 were analyzed.
The number of children followed at the centers decreased by 10% between 2018 and 2022 (892 to 799), while the total number of hospitalizations due to pulmonary exacerbations dropped from 471 to 163 — about 65%. Also, the proportion of children and young adults hospitalized two or more times in a single year declined significantly, from 45.2% in 2018 to 24.5% in 2022. The median duration of hospitalizations (12 vs. 10 days) was also lower in 2022.
A greater percentage of those hospitalized in 2022 identified as belonging to minority racial groups, highlighting ongoing health disparities in the [Trikafta] era.
Patients hospitalized in 2022 were younger than those hospitalized in 2018. The proportion of children younger than 6 was particularly higher, rising from 7% in 2018 to 20% in 2022. In addition, a higher proportion of hospitalized patients identified as Black and other races (28% vs. 14%) and Hispanic/Latino (41% vs. 30%) in 2022.
“A greater percentage of those hospitalized in 2022 identified as belonging to minority racial groups, highlighting ongoing health disparities in the [Trikafta] era,” the researchers wrote.
Patients hospitalized in 2022 more frequently had two mutations other than F508del, the most common CF-causing mutation, compared with those hospitalized in 2018, with the proportion of this group increasing from 19% to 38%.
“It is not surprising that children with CF hospitalized for pulmonary exacerbations more frequently have two non-F508del CFTR mutations. These individuals are less likely to qualify for [Trikafta] therapy, which has been shown to significantly reduce pulmonary exacerbations,” the team wrote.
Percentage of patients with bacterial infections decreased in 2022
The use of inhaled antibiotics and systemic, or bodywide, corticosteroids during exacerbations was similar in the two periods, although there was a trend toward higher use of CFTR modulators in 2022 (46% vs. 38%), with most patients in 2022 being treated with Trikafta.
Regarding bacteria identified in sputum samples, the most common types were methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa in both 2018 and 2022. However, in 2022, a significantly higher proportion of patients — 34% — had no bacteria detected, compared with 23% in 2018. A lower proportion were infected with methicillin-resistant Staphylococcus aureus in 2022 — 4.5% vs. 14% in 2018.
On the contrary, viral infections were more commonly detected in hospitalized patients in 2022, with this proportion increasing to 50% from 38%. However, the researchers noted that more children hospitalized for pulmonary exacerbations in 2022 underwent viral testing than in 2018.
During inpatient treatment, there were no differences in lung function between data from 2018 and 2022. Trikafta treatment did not impact the mean improvement in lung function of patients hospitalized in 2022.
“This study reveals the changing demographic and clinical profiles of children with CF hospitalized for pulmonary exacerbations in the era of [Trikafta] therapy,” the scientists wrote. “Most notably, children with CF from minoritized groups, who are less likely to be eligible for and treated with CFTR modulators including [Trikafta], compose a greater proportion of children with CF hospitalized for IV antibiotic treatment of pulmonary exacerbations as fewer White children with CF are being hospitalized.”
About the Author
