Trikafta, not pandemic isolation, drove real-world health gains for CF patients
Improvements were from treatment, not lockdown safety: US study
Written by |
The real-world health benefits that cystic fibrosis (CF) patients experienced when they started taking Trikafta (elexacaftor/tezacaftor/ivacaftor) during the COVID-19 pandemic were caused by the medication itself rather than lockdown safety precautions, according to a new U.S. study.
Because the U.S. Food and Drug Administration approved Trikafta in October 2019 right before global lockdowns began, questions remained over whether fewer lung infections were due to the drug or simply social distancing. By comparing treated patients directly with an untreated group during the same pandemic timeframe, researchers showed that Trikafta treatment — not pandemic isolation — drove the dramatic drop in respiratory complications, hospitalizations, and deaths.
“Overall, this study suggests that the benefits of [Trikafta] treatment on pulmonary, transplant, and mortality outcomes may be robust to potential bias from protective effects of the COVID-19 pandemic,” researchers wrote.
The study, “Clinical Outcomes in Concurrent Cohorts of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA)-Treated versus ELX/TEZ/IVA-Ineligible Individuals with Cystic Fibrosis in the US during COVID-19,” was published in Pulmonary Therapy. Vertex Pharmaceuticals, the company that sells Trikafta, sponsored the study and employs several of its authors.
How Trikafta targets CF symptoms
In CF, genetic mutations disrupt CFTR, a protein that helps regulate the movement of salt and water. People with CF don’t have enough working CFTR, which leads to their bodies producing unusually thick, sticky mucus. This increases the risk of lung infections and causes other CF symptoms.
A class of approved CF medications called CFTR modulators reduces abnormal mucus production by boosting the function of CFTR in people with eligible mutations. Trikafta is a triple-combination CFTR modulator, meaning it contains three medications that work together to improve protein function.
Clinical trials demonstrated that Trikafta effectively eased symptoms of CF and improved lung function, among other benefits. However, the timing of the medication’s U.S. rollout during the COVID-19 pandemic may make data on its efficacy in the real world less reliable.
“Questions have been raised as to whether the infection prevention measures put in place during the COVID-19 pandemic may have biased results observed in real-world studies of [Trikafta],” the researchers wrote.
To address these questions, the team used data from the U.S. Cystic Fibrosis Foundation Patient Registry to compare Trikafta’s effects to those of an untreated population during the same timeframe.
The investigators found 13,414 people with CF, 12 years or older, who started receiving Trikafta in the period from December 2020 to September 2021. They also found 1,600 people who weren’t eligible to take Trikafta during this time as a comparison group. Using statistical methods, they adjusted the analysis to account for differences in participant numbers across groups.
They began by comparing lung function using a measure called percent predicted forced expiratory volume in one second (ppFEV1). Over a mean follow-up of 1.83 years, participants who received Trikafta experienced a 6.2% increase in ppFEV1. Untreated participants saw a 3.13% decline.
This corresponded to a 99% slower decrease in ppFEV1 annually for the Trikafta group. “These findings are consistent with prior analyses of [Trikafta’s] impact on rate of lung function change,” the team wrote.
Next, the results showed that the rate of pulmonary exacerbations (flare-ups) requiring hospitalization or intravenous (into-the-vein) antibiotics was 0.17 in the Trikafta group, compared with 0.77 in the comparison group. This meant a 77% lower rate with treatment.
Correspondingly, the rate of lung transplants was 90% lower in the treatment group. Compared to the untreated group, the death rate was also 79% lower with Trikafta. In general, these results were similar to those seen in other studies. In addition, fewer people taking Trikafta had respiratory infection-causing microbes relative to the controls.
“This consistency across studies confirms that the observed benefits of [Trikafta] are not artifacts of COVID-19,” the researchers concluded.
The ability to directly compare treated and untreated individuals from the same time period was a strength of the study. However, it also led to a potential limitation, the team noted. The comparison group included people who weren’t eligible for Trikafta treatment. This means they had different genetic features than those of participants in the treatment group, which could have influenced the results.
However, based on previous studies, the team believed that the two groups had similar enough underlying disease features that the results would be comparable.
Leave a comment
Fill in the required fields to post. Your email address will not be published.