Study: Lower use of PERT in cystic fibrosis after Kalydeco’s US OK

Reduced usage might indicate the new therapy may lower EPI severity

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In the years after Kalydeco (ivakaftor) became available, the use of pancreatic enzyme replacement therapy (PERT) fell among people with cystic fibrosis (CF) in the U.S. who were eligible for the therapy.

That’s according to “Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries,” which was published in the Journal of Cystic Fibrosis.

Most people with CF have exocrine pancreatic insufficiency (EPI), where thick mucus blocks enzymes made in the pancreas from getting into the intestines to aid digestion. PERT is a standard treatment for EPI that contains working versions of pancreatic enzymes that can be delivered into the intestines.

CF is caused by mutations that result in low or no production of working CFTR protein. Kalydeco was the first widely approved CFTR modulator, a class of medications that can improve the protein’s function with specific CF-causing mutations.

Kalydeco was approved based on clinical trial data that showed it could improve lung function for those with eligible mutations. Its effects on EPI and other digestion-related symptoms weren’t fully characterized, however, leading scientists to analyze 10-year data from two CF registries — one from the U.S. with 35,741 people and one from the U.K. with 11,282 — to see if rates of PERT usage changed after Kalydeco became available.

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PERT use changes in US, UK after Kalydeco’s approval

In the U.S. CF Foundation Patient Registry, rates of PERT usage decreased steadily in the years after Kalydeco was approved among patients who were eligible for the therapy, whereas PERT use was largely stable over time in patients who weren’t eligible for Kalydeco.

In statistical models, Kalydeco-eligible patients were significantly less likely to be on PERT than ineligible patients, reaching statistical significance in the years 2016 and 2017. These trends suggest patients with access to Kalydeco had less need of PERT, implying the therapy may help lower EPI severity.

The U.K. database also indicated reduced PERT use among Kalydeco-eligible patients, but there was also a reduction in using PERT among patients who weren’t eligible for Kalydeco and the difference between the groups wasn’t statistically significant. Because the U.K. registry is smaller, these analyses had less statistical power to detect significant results, the researchers said.

“Associations between recorded ivacaftor [Kalydeco] treatment and PERT use suggest ivacaftor may reduce the severity of the exocrine pancreas insufficiency over time, however associations in the U.K. [CF registry] did not reach significance, highlighting inconsistency between registries,” the researchers wrote.

The scientists also compared rates of severe digestion-related hospitalizations before and after Kalydeco was approved, but they didn’t show consistent trends.

“Findings regarding unplanned [gastrointestinal] admissions were limited and did not demonstrate a clear effect of CFTR modulator treatment,” wrote the researchers, who noted severe digestion problems were rare overall, making it hard to draw statistically meaningful conclusions. They said more prospective research into how Kalydeco and other CFTR modulators may affect digestive health for eligible CF patients is needed.