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Landmark Cystic Fibrosis Clinical Trial Gives Patients Hope for Healthy Pregnancies

The FDA approval of TRIKAFTA has given patients with cystic fibrosis hope for healthy pregnancies. A clinical trial, co-led by UT Southwestern, will help measure the drug's safety during pregnancy.
The FDA approval of TRIKAFTA has given patients with cystic fibrosis hope for healthy pregnancies. A clinical trial, co-led by UT Southwestern, will help measure the drug's safety during pregnancy.
The FDA approval of TRIKAFTA has given patients with cystic fibrosis hope for healthy pregnancies. A clinical trial, co-led by UT Southwestern, will help measure the drug's safety during pregnancy.

Just 20 years ago, patients with cystic fibrosis (CF) were not expected to live past age 40, let alone carry a healthy pregnancy to term. Today, medical advancements such as the breakthrough CF drug TRIKAFTA are helping more adults live longer, healthier lives.

Unfortunately, none of these innovative therapies have been tested for safety in pregnancy. While most women with CF still ovulate – release eggs from their ovaries – complications from CF make conception more difficult. This may be due to thickened mucus in the cervix – a trademark of CF that can affect organs throughout the body.

But a new clinical trial co-led by UT Southwestern may give patients hope to start families they thought were out of reach.

Two years after a large clinical trial resulted in U.S. Food and Drug Administration (FDA) approval of TRIKAFTA, we are embarking on the landmark Prospective Study Evaluating Maternal and Fetal Outcomes in the Era of Modulators (MAYFLOWERS). The study will determine whether the drug is safe for pregnant and breastfeeding patients and their babies in the first two years after delivery.

The 40-site trial is funded by a $9 million grant from the CF Foundation. I am a principal investigator, along with Jennifer Taylor-Cousar, M.D., of National Jewish Health in Denver. Our research partners include the University of Washington and the Cystic Fibrosis Therapeutics Development Network Coordinating Center.

Watch Advances in Cystic Fibrosis Care and Life Expectancy

Anecdotally, we are seeing improved fertility among patients who take TRIKAFTA, an oral medication that targets a gene defect responsible for approximately 90% of the 80,000 CF cases worldwide. While more research is needed, experts believe TRIKAFTA, a three-drug combo that targets misfolded proteins, may reduce excess cervical mucus like it does throughout the body.

Preliminary data in animal models suggest no risk of birth defects from TRIKAFTA, and outcomes from a 2021 study by Dr. Taylor-Cousar and I show no significant complications in planned or unplanned pregnancies of patients who took the medication.

As the COVID-19 vaccine studies brought to light, pregnant women are generally excluded from clinical trials. While we understand wanting to avoid potential pregnancy complications, there may also be consequences in not investigating treatment options that may be safe in pregnancy, allowing patients to live healthy and fulfilling lives.

UT Southwestern’s Adult Cystic Fibrosis Clinic has an exceptional partnership with our maternal-fetal medicine (MFM) team. My Ob/Gyn colleague, Shivani Patel, M.D., joins us now to discuss how the clinical trial will work, what we know about CF and pregnancy today, and what to expect during prenatal care.

CF and Pregnancy: How will MAYFLOWERS trial work?

Shivani Patel, M.D.

Shivani Patel, M.D., a maternal fetal medicine specialist, will partner with the adult cystic fibrosis team to administer the clinical trial at UT Southwestern.

We estimate recruiting close to 300 women from 40 clinical trial sites to give us a large, reliable body of data of women on or off TRIKAFTA. Our research team will not intervene with patients’ care – the study is entirely observational. Each patient will determine the best course of care with her provider team, and we will analyze the data they report. Patients may choose whether to:

  • Take TRIKAFTA through the entire pregnancy
  • Stop taking TRIKAFTA at any point during the pregnancy
  • Not take it at all

The primary outcome will be whether the patient can maintain her lung function during pregnancy and includes all women with CF, even those not eligible for modulators. We will also learn whether patients can maintain their nutritional needs and whether they become ill and need antibiotics.

The research sites also will gather never-before-studied data such as patients’:

  • TRIKAFTA levels throughout pregnancy (and in their breast milk)
  • Liver function, including testing for inflammation
  • Glucose levels with continuous glucose monitors

In addition, the study will measure how CF-associated diabetes affects the patient, fetus, and baby, and it will monitor newborn health and infant milestones from delivery through 2 years old.

We understand patients with CF probably have a lot of questions about pregnancy and the potential role TRIKAFTA could play in making it safe, so here are some answers based on what we know now:

Can TRIKAFTA harm my baby?

While more research is needed, preliminary data (anecdotal and animal studies) suggest that TRIKAFTA does not increase the risk of pregnancy complications or birth defects. In a relatively short time, TRIKAFTA has dramatically changed the health trajectory for thousands of women with CF, and we hope to validate its safety in pregnancy with data gleaned from MAYFLOWERS.

What is pregnancy care like for patients with CF today?

Our maternal fetal medicine team works closely with Dr. Jain’s adult CF care team. If you become or want to become pregnant, we will collaborate with you to tackle some of the challenges of CF and prenatal care.

For example, patients with CF are more likely to develop severe infections that require strong antibiotics, many of which are not proven safe in pregnancy. Even azithromycin, commonly used to treat upper respiratory infections, is listed as “pregnancy class B,” with a slightly increased risk of pregnancy complications.

We’ll have deep conversations about your history of illnesses and treatments that have worked in the past. Together, we make an action plan for scenarios that might arise in pregnancy and countermeasures for effective, pregnancy-safe treatment.

Will I be considered a high-risk pregnacy?

Currently, pregnancies in patients with CF are considered high-risk pregnancies for a variety of reasons including that 20-50 percent of patients with CF also have diabetes. However, it will be interesting to see whether and how that changes after this trial.

Our MFM providers are experts in navigating pregnancy-safe treatments for common CF-related conditions such as diabetes, digestive, or lung problems. In the most complex cases, we have streamlined access to collaborate with Dr. Jain’s CF team and other specialists at UT Southwestern.

Since I have CF, will my baby have it, too?

Not necessarily. People with one copy of the mutation are carriers – they have the mutation but do not have CF. Those who have two copies of the mutation have cystic fibrosis.

It is rare that both parents have a CF-associated gene mutation. In cases where each parent has either one, there is a 25 percent chance your baby will have CF and a 50 percent chance your child will be a carrier but not have CF. Twenty-five percent will neither carry the defect nor have the disease.

We typically recommend that the partners of patients with CF get genetic testing so you can be prepared to potentially care for a baby who has the condition – as well as maintaining your own health.

How does CF affect breastfeeding?

It’s possible that mucus may build up in the milk ducts. A big challenge is the nutritional aspects. Breastfeeding requires more daily calories than pregnancy – approximately 500 extra calories a day. Many patients with CF are underweight due to gastrointestinal issues, which can make it tough to get sufficient calories outside of pregnancy.

MAYFLOWER research sites will gather information about the level of TRIKAFTA in patients’ breastmilk, as well as their babies’ developmental milestones through two years of age. These data will help us better understand impacts of TRIKAFTA, if any, on breast milk production and potential effects to infants.

What should I do first if I have CF and want to become pregnant?

Patients with or without CF tend to have better outcomes when they are as healthy as possible prior to pregnancy. Fortunately, many patients with CF are fairly health conscious already due to their condition.

Your first step should be to talk with your CF doctor about whether pregnancy is safe for you, based on your overall health. The doctor will refer you to our MFM team for preconception counseling, which will help you optimize your health before pregnancy. This includes maintaining healthy blood sugar levels, respiratory function, and weight.

We’ll also develop strategies to treat potential illnesses safely during pregnancy and discuss the impacts of pregnancy in your personal life. Having a new baby at home can affect your treatment – women tend to put their baby’s care ahead of their own, which can cause serious consequences for CF patients. We’ll help you design care plans for yourself and your baby if you get sick.

Women should not have to sacrifice their health to start a family if a potentially safe, effective treatment option is available. We hope MAYFLOWERS will confirm trends suggested by our preliminary data: that taking TRIKAFTA during pregnancy is safe for the mother, fetus, and infant. Enrollment will begin in summer 2021, and we are excited to help push this important research forward.

If you have CF and want to become pregnant – or if you’ve recently become pregnant – don’t stop your current treatment routine. Call your CF specialist to discuss pregnancy-safe options and get your pregnancy off to a healthy start.

To request an appointment or learn more about MAYFLOWERS, call 214-645-8300 or request an appointment online.