Use of routine therapies in CF lower with Kaftrio (Trikafta): Study
Airway medication, antibiotic use declined after starting new CFTR modulator
People with cystic fibrosis (CF) saw sustained reductions in the use of several other CF therapies after two years of treatment with Kaftrio (elexacaftor/tezacaftor/ivacaftor), with airway medications and antibiotics being the most reduced, according to a real-world study from Denmark.
“This study adds evidence of the real-world impact of [Kaftrio] beyond standard indicators of therapeutic effectiveness,” the researchers wrote. The study, “Impact of elexacaftor/tezacaftor/ivacaftor on utilization of routine therapies in cystic fibrosis: Danish nationwide register study,” was published in the Journal of Cystic Fibrosis.
CF is caused by mutations in the CFTR gene, which imparts instructions for producing the CFTR protein that helps certain cells regulate the flow of salt and water molecules. As a result of the mutations, the protein is faulty or missing, resulting in thick, sticky mucus accumulating in the lungs and other organs.
Treatment advances have improved survival for people with CF in recent decades, but this has been accompanied by a high treatment burden, with patients often needing to take a dozen other therapies to manage their condition.
Kaftrio, which is sold as Trikafta in the U.S., is a newer CFTR modulator that’s designed to help the defective CFTR protein work more effectively. Approved for patients ages 2 and older with eligible mutations, it’s been shown to effectively improve a number of clinical outcomes, including lung function and quality of life, and to reduce the number of pulmonary exacerbations.
Because the long-term efficacy of CFTR modulators like Kaftrio remains unknown, CF centers in Denmark recommend that patients stay on their routine CF therapies. These may include airway medications to help maintain lung health and function, antibiotics to fight off infections, medications to address gastrointestinal issues, and therapies to manage the abnormal production of certain hormones.
Changes since Kaftrio introduced
However, “treatment simplification is of high interest among [people with CF] and clinicians as the high treatment burden posed by current guidelines affect medication adherence and quality of life,” wrote researchers at the University Hospital of Copenhagen, who assessed the impact of Kaftrio on the real-world use of routine therapies. They enrolled all 351 Danish residents who started Kaftrio between September 2020 and November 2022, and who remained on it for at least three months.
The patients were a median age of 24 and most had two copies of the F508del mutation (76%). The follow-up included the two years before starting Kaftrio and two years after starting it.
Patients had a sustained reduction in airway medication and antibiotic use after starting Kaftrio, while gastrointestinal medications remained stable, and the use of endocrine medications increased slightly, the results showed.
Two years after starting Kaftrio, the proportion of patients using airway medications each year decreased from from 89.5% to 75.1%, while inhaled antibiotic use reduced from 59.5% to 42.9% . The use of oral antibiotics also decreased slightly, though the effects were more pronounced for inhaled ones.
The use of 4 out of 6 individual therapies was also reduced, with the greatest declines seen in the airway medications dornase alpha, which is sold as Pulmozyme and others, and beta-2 agonists such as Albuterol. There was also a decrease in antibiotics belonging to the class of macrolides and beta-lactam antibiotics, which include penicillin and cephalosporins, commonly used for lung infections in CF.
The probability of patients redeeming a prescription for routine treatments was significantly reduced for four drug classes after two years. The chances of redeeming one for airway medications was 76% lower; for inhaled antibiotics, 72% lower; for oral antibiotics, 51% lower; and for gastrointestinal medications, 34% lower. It remained unchanged for endocrine medications.
“Assuming prevalent users of a treatment are likely to redeem a prescription at least once per year, the reduced one-year prevalence” suggests that patients are discontinuing their treatments, the researchers wrote. “A substantial reduction in the use of several routine therapies was observed shortly after initiation of [Kaftrio] therapy despite unchanged guidelines, suggesting changes were mainly patient-driven or reflecting a lower symptom burden.”
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