Real-world Study Review: Kalydeco Improves Health Outcomes, Quality of Life

A review of 57 real-world studies found that people with cystic fibrosis (CF) who take Kalydeco (ivacaftor) experience improvements in lung function, nutrition, and quality of life (QoL).

Reduced healthcare system use, lower Pseudomonas aeruginosa prevalence, fewer organ transplants, and less mortality are other benefits associated with the Vertex Pharmaceuticals therapy.

The improvements were reported as early as one month after the start of treatment — and were sustained for up to five years.

The study, “Real-World Outcomes of Ivacaftor Treatment in People with Cystic Fibrosis: A Systematic Review,” was published in the Journal of Clinical Medicine.

CF is caused by mutations in the CFTR gene, which encodes a protein with a “gate” that is key in the movement of salts and water into and out of the body’s cells. Kalydeco targets CFTR mutations that cause the gate to stay closed, causing a buildup of mucus. Although clinical trials have demonstrated the treatment’s safety and efficacy, the long-term, real-world treatment outcomes have not been well-established.

Now, a team that included scientists at Vertex reviewed studies published between January 2012 and September 2019 of Kalydeco treatment in CF patients. A total of 75 publications covering 57 studies conducted in several countries — some were multinational — were reviewed. The studies had follow-up times of up to five years and included adults and children with CF.

Among the studies assessed, 39 (68%) were restricted to patients with a so-called gating mutation. Seven (12%) directly compared outcomes in patients treated or not treated with Kalydeco, and one long-term analysis in the U.S. and the U.K. tracked disease progression in people given Kalydeco over at least four years.

The studies consistently showed improved lung function in Kalydeco-treated CF patients, beginning as early as one month of treatment and remaining above pre-study levels at one year of treatment. In the two studies that assessed CF patients with severe lung disease, Kalydeco treatment significantly increased lung function compared with non-treated patients. 

Likewise, Kalydeco treatment was associated with a decrease in pulmonary exacerbations in the year after the start of use, as compared with the year before the therapy was given. Similar results were reported in CF patients with severe lung disease. In the long-term analysis, Kalydeco-treated patients had a significantly lower risk of pulmonary exacerbations than non-treated patients. 

Weight loss and poor nutrition are common in CF patients. In Kalydeco-treated CF patients, increased weight and body mass index — a measure of body fat — were reported as early as one month into treatment, with sustained improvements for up to five years. In an Australian study, CF patients with severe lung disease experienced a similar increase. That improvement was maintained at one year of treatment. 

Kalydeco use also was associated with decreased all-cause hospitalizations, less inpatient treatment due to pulmonary exacerbations, and lowered antibiotics use from six months to five years into the treatment. Similar results were found among patients with severe lung disease. In a study in the U.K and Ireland, Kalydeco use also was associated with fewer organ transplants for more than three years (38 months) of treatment.

Prevalence of P. aeruginosa, a key bacteria in CF lung infections, also was reduced in Kalydeco-treated patients. Multiple studies reported sustained improvements in respiratory symptom-related quality of life and quality of health in people given this therapy.

Of the seven studies that reported treatment-related adverse events within eight months to two years into the therapy’s use, none reported new safety concerns. Decreased mortality was reported in CF patients on Kalydeco over one year in two studies — and for up to five years in the long-term analysis. 

“Our findings support long-term ivacaftor [Kalydeco] use to improve clinical markers of disease severity, slow the progression of CF, and potentially reduce disease burden, while allowing [people with] CF to have better survival outcomes and improved QoL,” the investigators wrote.

Among the study’s limitations, said the scientists, were inconsistencies in study design and reported outcomes across the reviewed publications, use of interim results from two studies, and a lack of non-treated control groups in most of the studies.

“Despite these limitations, the improvement in outcomes noted in this literature review of real-world evidence is consistent with results observed in ivacaftor clinical trials,” the researchers added.