Baltimore, MD – A large U.S. registry study has found that people living with Cystic fibrosis who are treated with CFTR modulator therapies experience a significantly lower risk of death compared with untreated patients, with an overall reduction of 66% over an eight-year follow-up period.
The findings, published in CHEST, represent one of the most comprehensive real-world evaluations to date of how CFTR modulators affect long-term survival in cystic fibrosis. Researchers from Johns Hopkins University described the study as the largest registry-based cohort with the longest longitudinal follow-up examining mortality outcomes for these therapies.
Real-world survival benefit confirmed
CFTR modulators are designed to correct the malfunctioning CFTR protein responsible for cystic fibrosis, helping reduce mucus buildup and slow disease progression. These treatments include:
- Kalydeco (ivacaftor)
- Orkambi (ivacaftor/lumacaftor)
- Symdeko (ivacaftor/tezacaftor)
- Trikafta (ivacaftor/tezacaftor/elexacaftor)
A newer therapy, Alyftrek (vanzacaftor/tezacaftor/deutivacaftor), was approved after the study period and was not included in the analysis.
The study analyzed data from 25,103 patients recorded in the U.S. Cystic Fibrosis Foundation Patient Registry between 2012 and 2022, covering 178,835 clinical and telehealth visits. Of these patients, 18,056 initiated CFTR modulator treatment.
Significant reduction in mortality
Over the study period, 15% of participants died. However, outcomes differed substantially between treated and untreated groups:
- At 1 year: 0.4% mortality in treated patients vs. 1% in untreated
- At 5 years: 2.5% vs. 8.1%
- At 8 years: 4.1% vs. 11.4%
Overall, treatment was associated with a 66% lower risk of death over eight years.
Researchers noted that outcomes varied depending on age at treatment initiation, with risk reductions ranging from 49% in adolescents (12–17 years) to 72% in adults aged 18–29, and 70% in patients aged 30 and older.
Benefits consistent across sexes
The survival advantage was similar between sexes, with a 69% lower risk of death in males and a 65% reduction in females—differences that were not statistically significant.
The study authors emphasized that while clinical trials have previously demonstrated improvements in lung function and other short-term outcomes, long-term survival benefits had not been well characterized until now.
Experts highlight long-term impact
“Our study is the largest registry-based cohort with the longest longitudinal follow-up examining the real-world effectiveness of CFTR modulator therapies on death to date,” the researchers wrote. They added that improved understanding of survival benefits can help patients, families, and clinicians better anticipate long-term care needs as life expectancy increases.
They also noted that about 90% of individuals with cystic fibrosis are now eligible for CFTR modulator therapy, although access remains limited for some due to genetic non-responsiveness, intolerance, or high cost.
Looking ahead
Among treated patients, 6.7% discontinued therapy after a median of 1.9 years, while those who remained on treatment were followed for a median of 4.2 years.
The researchers concluded that expanding access to CFTR modulators could further reduce cystic fibrosis-related mortality, while ongoing development of next-generation therapies may help reach patients who currently cannot benefit from existing options.
Footnote
The study, “Effectiveness of CFTR modulator therapy on risk of death for individuals with cystic fibrosis,” was published in CHEST.
Contact
Katherine E. Kurgansky – PhD, MPH
Johns Hopkins Bloomberg School of Public Health