In real-world use, Kaftrio helps children keep lung function stable

Unlike in clinical trials, dramatic changes not likely for most young CF patients

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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While Kaftrio — sold as Trikafta in North America — can improve lung function in children with cystic fibrosis (CF), treatment effects are unlikely to be as dramatic in real-world practice as those reported in clinical trials.

Rather, for eligible children without substantial lung problems, Kaftrio’s use can help to stabilize lung health. But it probably won’t lead to the substantial gains seen in trials that specifically enrolled young patients with poor lung function, scientists in the U.K. report.

“The importance of stability and maintenance of normal lung function … is perhaps an important difference in the ‘real‐world’ approach to young children with CF, rather than seeking the large improvements seen in trials,” the researchers wrote.

Their report “Lung clearance index (LCI2.5) changes after initiation of Elexacaftor/Tezacaftor/Ivacaftor in children with cystic fibrosis aged between 6 and 11 years: The ‘real-world’ differs from trial data,” was published in Pediatric Pulmonology.

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Kaftrio/Trikafta is a triple combination CFTR modulator

Kaftrio, or Trikafta, contains a combination of three CFTR modulators — elexacaftor, tezacaftor, and ivacaftor — that can boost the functionality of the mutated CFTR protein in people with CF caused by specific mutations. The therapy is sold by Vertex Pharmaceuticals, which was not directly involved in this study.

In the U.K., as in various other countries, Kaftrio is authorized for use in eligible children as young as age 2. Its approval was supported by clinical trials that demonstrated Kaftrio/Trikafta improved a lung function measure called the lung clearance index or LCI.

LCI basically measures how long it takes a gas to clear from the lungs, and a lower score means the lungs are functioning more efficiently. In the trials, average LCI scores started around 10, and they improved by roughly two points after six months of treatment.

Scientists at the Royal Hospital for Children and Young People in Edinburgh reported LCI outcomes for 12 children with CF, ages 6 though 11 (the childhood age range first eligible for Kaftrio), who began treatment at their center between March and April 2022. All of the children underwent LCI assessment before starting Kaftrio, then again about eight months later.

Results showed that LCI scores tended to improve with Kaftrio, but score changes were fairly modest — 0.7 on average — and not statistically significant.

Other measures of lung function, including the forced expiratory volume in one second, also tended to improve after patients started on Kaftrio. But again the difference was small, especially compared to what was seen in clinical trials.

Most children in the report started treatment with fairly normal lung function

Researchers suggested the reason for this difference lies in clinical trials of Kaftrio specifically having enrolled patients who already had fairly poor lung function — a trial design that can lead to more dramatic effects. In the real world, children with CF often start treatment before they have substantial lung problems.

Specifically, the researchers highlighted that the average LCI score for their children was about seven, which is within the normal range, prior to starting on Kaftrio. They also noted that most in their study wouldn’t have been eligible to participate in Kaftrio/Trikafta trials, which required patients to have an LCI score of 7.5 or higher.

Several of the children in this report also had been on other CFTR modulators prior to starting on Kaftrio, and the software used to calculate LCI in clinical practice differs from that used in trials, the scientists added. These factors, they said, also may contribute to differences in outcomes between clinical trials and the real world.

As this report was limited to a dozen patients, the scientists noted that its findings should be treated with appropriate caution.

Still, “the ‘real‐world’ includes children with CF whose baseline LCI is lower than children included in phase 3 trials …and levels of prior modulator treatment may also be different to trial populations,” the team concluded. “Put simply, the ‘real-world’ is different from clinical trials.”