CF Patients on Kalydeco Healthier With Fewer Flares, Study Reports

Kalydeco (ivacaftor) safely and effectively improved lung function, growth, and nutrition in children and adults with cystic fibrosis (CF), while reducing rates of pulmonary flares and hospitalizations, according to a real-life study in France.

These findings were consistent with those reported in previous clinical trials and real-world studies, confirming the therapy’s benefits both in terms of patients’ health and the use of healthcare resources.

The study, “Real-World Long-Term Ivacaftor for Cystic Fibrosis in France: Clinical Effectiveness and Healthcare Resource Utilization,” was published in the journal Pulmonary Therapy.

CF is caused by mutations in the CFTR gene, affecting the production of functional CFTR, a protein “gate” essential for the movement of salts and water into and out of cells.

Kalydeco, by Vertex Pharmaceuticals, is a CFTR potentiator that targets CFTR gating mutations, or those that cause the gate to stay closed, resulting in mucus buildup. It is approved in the U.S. and in Europe for patients, 4 months and older, with one of 97 mutations.

Although the safety and effectiveness of Kalydeco were established in controlled clinical trials, real-world evidence in a broad patient population is essential and can be limited.

BRIO (Cystic FiBRosis In Observation) was an observational study designed with Vertex to evaluate Kalydeco’s safety, effectiveness, and associated healthcare resource utilization in children and adults with CF carrying amenable gating mutations.

A total of 129 CF patients (120 already on Kalydeco) were recruited at 35 centers in France from March 16, 2016, to Dec. 2, 2019. Patient data were collected (retrospectively and/or prospectively) for up to one year prior to Kalydeco initiation through up to two years after enrollment.

Patients started using Kalydeco at a mean age of 19.1 (range, 2–64 years), and most were children or adolescents (58.9%) and carried a G551D mutation (64.3%). Treatment was given for a mean of 52.7 months, or over four years (range, 20–92 months).

This made BRIO the largest study of Kalydeco-treated CF patients in France, and the first real-life study in French children younger than 12 (comprising about 40% of participants).

The trial’s main goal was to assess changes in lung function, as measured by predicted forced expiratory volume in 1 second. Secondary goals included changes in growth, nutrition, the rate of pulmonary exacerbations (symptom worsening), lung microbiology, safety, and use of healthcare resources in terms of hospitalization, IV antibiotics, and concurrent symptomatic treatments.

Results showed that Kalydeco, within the first six months of its use, strongly improved patients’ lung function, growth, and nutrition, and that these improvements were sustained up to three years of treatment.

These benefits are relevant, as they are associated with improved survival in this patient population, the team noted.

Over time with Kalydeco’s use, a lower proportion of patients tested positive for lung infections (90.9% pre-treatment vs. 75.8% to 83.3% post-treatment), particularly of Staphylococcus aureus and Pseudomonas aeruginosa. Infections with either bacterium “are associated with poor outcomes and increase treatment burden, often requiring repeated antibiotics courses,” the researchers wrote.

Kalydeco treatment was also associated with a 43% drop in both the annualized rate and duration of pulmonary flares, and a 75% reduction in the annualized rate of pulmonary exacerbations requiring hospitalization.

The frequency of hospitalizations also fell by 52%, while duration of hospitalizations and the use of IV (into-the-vein) antibiotics dropped by 61%, indicating lesser reliance on healthcare resources.

These measures were based on changes between one-year periods before and after initiating treatment.

Kalydeco was generally well-tolerated, with no new safety concerns identified. A total of six (4.7%) patients experienced adverse events deemed related to treatment, including weight gain, bleeding, and rash.

Seven (5.4%) patients discontinued Kalydeco, and 22 (17.1%) interrupted treatment, with adverse events being the most common reason (3.1%).

These findings “are highly clinically relevant and further support the benefits of [Kalydeco] and the potential to alter the clinical course of CF disease,” the researchers wrote. Reduced healthcare resources utilization the therapy was also confirmed, they added.

While these results were consistent with those reported in previous trials and real-world studies, the team noted that they may not be generalized to CF patients in other countries due to differences in standards of care and health systems.