Cystic Fibrosis Care is Starting Earlier Than Ever With CFTR Modulator Therapy

Few families experience advances in care as directly as those who face the same diagnosis twice. Abi, a patient at the Colorado Fetal Care Center (CFCC), experienced firsthand how drastically and quickly cystic fibrosis (CF) treatment has evolved. From one pregnancy to the next, she saw CF care go from managing complications after birth to preventing them before her baby was born.

Managing CF complications after birth 

Jordana Hoppe, MD, a pulmonologist at the Breathing Institute, has cared for Abi’s family since her first child, Meryl, was born with cystic fibrosis. CF is a genetic condition that causes mucus to become thick and sticky. As it builds up, it can clog the lung, pancreas and other organs. Meryl’s case was complicated by meconium ileus, a bowel blockage that develops before birth, caused by CF. Meconium ileus is among the earliest and most severe manifestations of CF. It occurs in up to 20% of babies born with the condition. Shortly after Meryl was born, she needed surgery and spent the first three months of her life in the neonatal intensive care unit.

“Because of feeding challenges following surgery, she ended up needing a g-tube placement prior to being discharged. For a long time, she had difficulties with growth, weight gain and feeding related to her meconium ileus,” Dr. Hoppe says.

Preventing CF complications before birth with CFTR modulator therapy  

Years later, when Abi became pregnant with her third child, Simone, she underwent routine prenatal blood testing for CF. During an ultrasound, doctors noticed bright spots on the fetal intestines — findings consistent with meconium ileus. Because of the family’s familiarity with CF, they wanted to do everything possible to prevent Simone from facing the same early complexities of the condition.

That opportunity came through an emerging, carefully monitored approach: prenatal treatment with elexacaftor/tezacaftor/ivacaftor, also known as ETI or Trikafta. Trikafta, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, is currently available as a treatment for eligible people with CF two years and older. It was approved by the FDA in 2019, after Meryl was born.

Can Trikafta treat cystic fibrosis before birth? 

Evidence pointing to the benefits of prenatal Trikafta use first emerged when people with CF began becoming pregnant more easily. As these pregnancies boomed, early observational studies documented improved fetal outcomes in pregnant people with CF using Trikafta, including reversal of meconium ileus. Because of these promising findings, researchers in our Colorado Fetal Care Center and Breathing Institute began to evaluate using Trikafta prenatally. Abi began taking Trikafta at 27 weeks pregnant, in the hopes it would impact Simone’s symptoms and outcomes.

“This is a noninvasive fetal therapy,” says Michael Zaretsky, MD, fetal surgeon and maternal fetal medicine specialist. “We can give a drug to the mother that crosses the placenta and can have a profound impact.”

Drs. Hoppe and Zaretsky monitored Abi and Simone throughout her pregnancy to assess both her and Simone’s bowel and liver function. Abi delivered at the CFCC at 37 weeks. At birth, Simone had an initial delay in passing stool, but the neonatal intensive care was able to clear the blockage with enemas rather than surgery. Early testing also showed pancreatic insufficiency, which affects about 85% of infants with CF. The team treated this as well, utilizing pancreatic enzymes. Simone went home within just a few days of birth — a striking contrast to Meryl’s prolonged NICU stay.

“Because of the Trikafta, Simone’s meconium ileus was not nearly as severe,” Dr. Hoppe says. “Without Trikafta, she was likely going to need more intervention and a longer NICU stay.” 

Contributing to the evidence for prenatal CF care 

Abi continued taking Trikafta until Simone was 10 months old, and according to Dr. Hoppe, evidence showed that Simone received Trikafta’s benefits through breastmilk, resulting in lower sweat chloride values. Sweat chloride concentration, the amount of chloride in a person’s sweat, is elevated in those with CF. For someone with two copies of the F508del mutation like Simone, they’d likely have a sweat chloride value of around 100.

“When we did her sweat test when she was a month old, she had only been receiving Trikafta through breastmilk. Her sweat test was only 65 — only 5 mmol/L above the clinical threshold for CF,” Dr. Hoppe says.

With the Trikafta exposure in breastmilk, Simone’s pancreatic function also began to improve, allowing her to absorb nutrients and grow properly. Simone no longer needs to take pancreatic enzymes every time she eats. And she’s since met typical growth milestones, reducing the intensity of her early CF care. 

Beyond Simone’s outcome, Abi’s experience has contributed to the growing evidence supporting early CF treatment. Our researchers published Abi’s case, documenting the side effects, barriers to care and successes she experienced, along with two other patients treated at the CFCC, in the Journal of Cystic Fibrosis. 

“We are tracking these cases with a registry,” Dr. Zaretsky says. “We have centers that are inputting data from a few institutions. That’s a growing list of patients who have been exposed to these drugs.”

Understanding the importance of cystic fibrosis carrier testing 

Drs. Zaretsky and Hoppe are hopeful that prenatal Trikafta will continue to change early complications associated with CF. However, a significant barrier is identifying affected pregnancies early enough for intervention.

Only 37% of patients opt to have the CF carrier screening. After specialists identify parents as carriers, amniocentesis can confirm a CF diagnosis. In many cases, however, CF is diagnosed only after bowel abnormalities appear on an ultrasound. This is often later in pregnancy and narrows the window for earlier treatment.

“My dream would be that we know that carrier status of the parents and that leads to an earlier prenatal diagnosis,” Dr. Zaretsky says.

As researchers document more cases like Abi’s, clinicians hope the evidence will not only expand access to the treatment but also shift how and when they diagnose CF, giving more children a chance for a healthier start.

“I hope that our story can move some of that closer,” Abi says. “For us, it gives us greater purpose if we can help change that for people.”