HJAR Jul/Aug 2026

46 JUL / AUG 2026 I  HEALTHCARE JOURNAL OF ARKANSAS ADH CORNER COLUMN CHILDREN’S HEALTH TRIPLE-COMBINATIONTHERAPY (TC), now a primary approach to cystic fibrosis (CF) therapy using cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs, has been a life-changing discovery, improving lung function and overall health for nearly 90% of eligible people with CF. 1 Some estimates suggest that modulator therapy could add decades to the median lifespan for half of children who begin this therapy early. 2 However, not everyone will achieve that, and a substantial portion won’t benefit from it due to a lesser response or side effects. Understanding the underlying causes of the wide variance in responses is a priority to ensure more people benefit from the therapies, including subpopulations pre- viously ineligible. Multiple ongoing studies aim to measure the long-term impact of CFTR modulators, especially as the U.S. Food and DrugAdmin- istration approved those therapeutics for use among younger populations. In studies I have been directly involved in, we have consis- tently seen wide variation in drug concentra- tions in multiple modulator therapies. When we measured drug levels in the blood, we found big differences from person to per- son — even though everyone was taking the same approved dose. Depending on the drug, anywhere from about 25% to 86% had one or more compounds in the therapy that had levels that were either too low or too high compared to the “ideal” range. Patients with lower drug levels showed less improvement in sweat chloride, a key biomarker of CFTR function that is associated with other health outcomes in CF. However, having drug levels higher than the ideal range didn’t give any extra benefit. The connection between drug level and sweat chloride remained clear when we looked across all patients. Some patients aren’t getting enoughmedicine to achieve the full benefit, while others may receive more than they need without extra gain. 3 These findings support the idea that tailoring drug levels to therapy ensures a balance of benefit and safety. In 2024, Arkansas Children’s Research Institute (ACRI) received $2.9 million from the National Institutes of Health for the EN- ACT study focused on concentration data and dose titration to optimize the clinical response to TC. 4 Improving Precision Therapeutics in Cystic Fibrosis Care: A RESEARCH UPDATE