Keftrio, Tricafta in the US, helps women during pregnancy safely | Cystic fibrosis patient shows better fertility, weight gain and lung health

Keftrio use (elexacaftor, tezacaftor, and ivacaftor), sold in the United States TricaftaI helped a woman with her cystic fibrosis (CF) She gets pregnant easily and stays healthy throughout pregnancy and childbirth, according to a case report from France.

The woman had experienced in a previous pregnancy, due to impaired fertility and repeated episodes of cystic fibrosis, before starting the triple combination therapy that was previously developed and marketed Vertex Pharmaceuticals. Both the children and the woman were discharged from the hospital and returned home within a month of her birth.

Our case shows a real benefit for the mother without revealing of No negative consequences for the fetus,” the researchers wrote.

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the report “Comparison of two pregnancies with and without elexacaftor-tezacaftor-ivacaftor in a woman with cystic fibrosis.It was published as a letter in the magazine Respiratory Medicine and Research.

Pregnancy rates among women with cystic fibrosis have increased in recent years as treatment options have improved. The report indicated that 50 pregnancies were identified among this group of patients resulting in 33 live births in France in 2019.

Keftrio started eight months after the first difficult pregnancy

Captrio, A changer Therapy, among these options. It helps the defective CFTR (cystic fibrosis transmembrane conductance regulator) protein The cause of the disease, work more effectively. Keftrio was approved in France in 2020, and has been available under compassionate use for patients with advanced cystic fibrosis since 2019.

However, there is little data currently available on the use of CFTR modulators in pregnant women, and the true effect on mothers and children. [fetal prognosis] The researchers wrote that the gestation period is still unclear.

A team at Hôpital Foch, near Paris, described two pregnancies, one before and one after starting Keftriou, to a woman with cystic fibrosis who was 32 years old at the time of her second pregnancy. The woman had two copies of F508del Mutation (the most common cause of cystic fibrosis CFTR genetic mutation), respiratory impairment, chronic airway infection Pseudomonas aeruginosa Resistant to methicillin aureus bacteriaAnd the exocrine pancreatic insufficiencyAnd the CFTR .-related diabetes.

Exact dates of care provided were not included in the report.

Her first pregnancy came after seven years of infertility treatment and several years in the laboratory Fertilization cycles. During the first trimester of pregnancy, her treatments included pancreatin, montelukast, azithromycin, L-thyroxine, insulin therapy, daily respiratory physiotherapy, and enteral feeding.

She gained a total of 3 kg (about 6.6 lbs) during pregnancy. Diabetes has, with measuring blood sugar levels using glycated hemoglobin level She was 6.6% before pregnancy, consistent with a diabetes diagnosis, and 5.7% shortly before her birth, consistent with prediabetes.

Predicted the percentage of forced expiratory volume in one second (ppFEV1), a measure of lung health, was 50% before pregnancy. Scientists reported that she had three pulmonary episodes, a sudden worsening of her respiratory symptoms, at 11, 20 and 25 weeks of pregnancy she was treated with antibiotics, including an intravenous regimen.

A fourth exacerbation after seven months of her gestation (28 weeks gestation) necessitated hospitalization, treatment with intravenous antibiotics, which was continued until delivery, and nocturnal oxygen.

The baby was born after 33 weeks of gestation by caesarean section, which necessitated a drop in the woman’s ppFEV1 ratio to 31%. The baby was born weighing 2.37 kg (approximately 5.2 lb) and had transient respiratory distress syndrome, and the baby was treated with continuous positive airway pressure for 27 hours. Mother and child were released to home care 22 days after birth.

The ‘positive effect’ on women’s fertility and overall health

After eight months, the woman began using Keftrio-elixacaftor at a dose of 200 mg and tezacaftor at a dose of 100 mg, both taken once daily, and ivacaftor at a dose of 150 mg every 12 hours. You became pregnant naturally 20 days after starting treatment.

This ease of conception and the fertility that it involves.”Seems like a big difference” with the first pregnancy, the scientists wrote.

After an ethical discussion about patient health and the effect of correctors [elexacaftor and tezacaftor]We agreed that the benefits of CFTR modifiers outweigh any potential unknown risk to the child.”

Other treatments remained the same as those used in the first pregnancy, except that she no longer required respiratory physiotherapy and enteral nutrition.

Her pFFEV1 increased to 53% one month after starting Keftrio, increased to 60% before delivery, and gained 10 kg during this pregnancy. Her hemoglobin A levels were normal at 5.5% on tests done before pregnancy and delivery, indicating that she did not have diabetes.

She was treated for one pulmonary attack at home with oral antibiotics, and reported respiratory discomfort at her 8th month of gestation (33 weeks gestation).

Her baby, a boy, was born by caesarean section early, at 34.5 weeks gestation, due to the mother’s ruptured membranes and an abnormal fetal heart rate. He weighed 2.86 kg and was also suffering from transient respiratory distress syndrome who was treated for seven hours with CPAP. Mother and baby returned home 11 days after birth.

Our case shows a positive effect of [Kaftrio] on fertility. This resulted in a spontaneous pregnancy shortly after starting treatment which may be due to improvements in cervical mucus consistency and pH,” the researchers wrote.

Abnormal CFTR function is associated with impaired fertility due to an imbalance in the viscous pH of cervical mucus. “The current, as yet unproven, hypothesis is that CFTR modulators reduce viscosity and increase pH in cervical mucus secretions,” the researchers added.

They also noted that the apparent ease of fertility in this pregnancy may be due to the women’s better nutritional status after starting Ceftrio.

Use of captrio here was also associated with ppFEV1 improvements and fewer and less severe pulmonary exacerbations. “The patient has not had such good results before,” the researchers wrote.

The team noted that the first baby was still healthy at 18 months of age, and the other was still being monitored even though he was “born without evidence of a congenital malformation”.

In the United States, 45 pregnancies and 29 live births were reported in 2020 among cystic fibrosis patients using Tricavta.

An observational study called Maternal and Fetal Outcomes in the Age of Modifiers (Mayflowers, NCT04828382), which began in 2021, evaluated the use of CFTR-modulatory therapy on lung function during pregnancy and lactation. The study enrolls eligible women with cystic fibrosis in Locations across the United StatesIt is expected to end in 2025.