HJAR Jul/Aug 2026

HEALTHCARE JOURNAL OF ARKANSAS I  JUL / AUG 2026 47 could ensure that all eligible children and adults, including those pregnant or post- partum, experience the therapy’s benefits while limiting adverse effects. Pharmacogenomic approaches have shown early promise. Data from the ENACT study and prior studies indicates opportu- nities to implement pharmacogenomics in CF care. 7 The evidence base is still limited, so it’s best to be cautious about overinter- preting early studies. Guidance from drug labeling and groups such as the Clinical Pharmacogenetics Implementation Con- sortium (CPIC), the FDA, and other regula- tory agencies should shape decision-making where genetic variation is known to affect drug choice or dosing. Collaboration between the University of Arkansas for Medical Sciences, as the central institutional review board, andACRI, as the central data and study coordinating center for the ENACT and ELECTRA studies, has yielded an infrastructure that speeds mul- tisite enrollment, standardizes assays, and centralizes high-quality data management. Working with sites across the nation enables us to contribute to the trend of rapidly ad- vancing CF care, which will continue to im- prove lung function and increase life ex- pectancy for patients with cystic fibrosis. n REFERENCES 1 Peter G. Middleton et al., “Elexacaftor– Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele,” New England Journal of Medicine 381, no. 19 (2019): 1809–1819, https:// doi.org/10.1056/NEJMoa1908639; Peter J. Barry and Jennifer L. Taylor-Cousar, “Triple Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in the Real World — Opportunities and Challenges,” Current Opinion in Pulmonary Medicine 27, no. 6 (2021): 554–566, https://doi.org/10.1097/ MCP.0000000000000819. 2 Alicia Lopez et al., “Elexacaftor/Tezacaftor/ Ivacaftor Projected Survival and Long-Term Health Outcomes in People with Cystic Fibrosis Homozygous for F508del,” Journal of Cystic Fibrosis 22, no. 4 (2023): 607–614, https://doi. org/10.1016/j.jcf.2023.02.004. 3 Ashritha R. Chalamalla et al., “Impact of CFTR Modulator Concentrations on Clinical Response in Cystic Fibrosis,” European Respiratory Journal 67, no. 6 (2026): 2501594, https://doi. org/10.1183/13993003.01594-2025. 4 National Library of Medicine, “Ensuring Access to Optimal Therapy in CF: The ENACT Study,” ClinicalTrials.gov, Identifier NCT07148739, last updated June 2, 2026, https://clinicaltrials.gov/ study/NCT07148739; “NIH Awards Arkansas Children’s Research Institute $2.9 Million to Explore How Critical Cystic Fibrosis Therapy Can Help More Patients,” press release, Arkansas Children’s, October 17, 2024, https://www. archildrens.org/news/releases/2024/nih-awards- millions-to-ACRI-for-cystic-fibrosis. 5 Natalie R. Rose et al., “Pharmacokinetic Variability of CFTR Modulators from Standard and Alternative Regimens,” Pulmonary Pharmacology & Therapeutics 86 (2024): 102301, https://doi.org/10.1016/j.pupt.2024.102301. 6 NIH RePORTER, “The ELECTRA Pregnancy Study,” Project number 1R01HD117940-01, https://reporter.nih.gov/project-details/ 11105425#description; “ACRI Launches Groundbreaking Study to Tailor Cystic Fibrosis Care for Moms and Babies,” press release, Arkansas Children’s, September 18, 2025, https:// www.archildrens.org/news/releases/2025/acri- cystic-fibrosis-study. 7 Jennifer S. Guimbellot et al, “Novel Applications of Biomarkers and Personalized Medicine in Cystic Fibrosis,” Clinics in Chest Medicine 43, no. 4 (2022): 741–753, https://doi.org/10.1016/j. ccm.2022.06.005; Justin D. Anderson et al., “Pharmacogenetic Actionability and Medication Prescribing in People with Cystic Fibrosis,” Clinical and Translational Science 16 (2023): 807– 817, https://doi.org/10.1111/cts.13479. Jennifer S. Guimbellot, MD, PhD, is a pediatric pul- monologist and chief of pulmonology and sleep medicine at Arkansas Children’s and a professor of pediatrics at the University of Arkansas for Medical Sciences. She is also the principal investigator for multiple studies coordinated through the Arkansas Children’s Research Institute. Jennifer S. Guimbellot, MD, PhD Chief of Pulmonology and Sleep Medicine Arkansas Children’s The first part of ENACT focuses on better understanding what factors influence con- centration variability in a large population. The second part of ENACT tests whether it is useful to use concentration-guided dos- ing titration, targeting feasibility, safety endpoints, and repeated measures of lung function, sweat chloride, and mental health outcomes. In an earlier study, some reduced- dose patients maintained concentrations near effect thresholds and reported side ef- fect mitigation, but not everyone did. 5 We need to determine whether this is a viable, evidence-based strategy to manage side ef- fects while maintaining the drug’s positive effects. At this point, it’s too early to know if rou- tine therapeutic drug monitoring (TDM) will be necessary or helpful in CF because the data are still developing and there’s not yet enough evidence to support it as a standard tool. However, triple-combination modu- lators have transformed CF care, and pa- tients who do not tolerate the standard dose sometimes improve with a dose reduction. In those cases, providers should closely monitor lung function, sweat chloride, and clinical outcomes. Studying CFTR Treatment in New Subpopulations CFTR modulator therapies have made it easier for people with CF to get pregnant. One goal of the ELECTRA study, launched in 2025, is to discover how the body uses and breaks down CFTR modulator drugs during and after pregnancy. 6 Moving from uniform dosing to precision therapeutics