Prospectively evaluating maternal and fetal outcomes in the era of CFTR modulators: the MAYFLOWERS observational clinical trial study design

Jain, Raksha; Magaret, Amalia; Vu, Phuong T.; VanDalfsen, Jill M; Keller, Ashley; Wilson, Alexandra; Putman, Melissa S.; Mayer-Hamblett, Nicole; Esther, Charles R.; Taylor‐Cousar, Jennifer L.

doi:10.1136/bmjresp-2022-001289

Cited by 27 publications

(19 citation statements)

References 60 publications

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“…Long-term pharmacovigilance is needed to understand the safety of these drugs including drug-drug interactions and effects such as weight gain, elevated blood pressure, mental health effects, and liver function abnormalities . The long-term safety and effectiveness of CFTR modulators prenatally and in infants younger than 4 months is unknown …”

Section: Discussion and Observationsmentioning

confidence: 99%

“…94 The long-term safety and effectiveness of CFTR modulators prenatally and in infants younger than 4 months is unknown. 108 Adults comprise 58.3% of the total US cystic fibrosis population. As this population ages, expanded services will be needed across multiple subspecialities to manage comorbidities and agerelated complications including gastrointestinal cancers, diabetes, obesity, and hypertension.…”

Section: Practical Considerations and Application Of Evidencementioning

confidence: 99%

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Cystic Fibrosis

Ong

Ramsey

2023

JAMA

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ImportanceCystic fibrosis, a genetic disorder defined by variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affects more than 30 000 individuals in the US and approximately 89 000 worldwide. Absent or decreased function of the CFTR protein is associated with multiorgan dysfunction and shortened life expectancy.ObservationsCFTR is an anion channel in the apical membrane of epithelial cells. Loss of function leads to obstructed exocrine glands. Of people with cystic fibrosis in the US, approximately 85.5% have the gene variant F508del. Manifestations of cystic fibrosis in patients with the F508del gene variant begin in infancy with steatorrhea, poor weight gain, and respiratory symptoms (coughing, wheezing). As people with cystic fibrosis age, chronic respiratory bacterial infections cause loss of lung function and bronchiectasis. With the availability of universal newborn screening in multiple countries including the US, many people with cystic fibrosis are asymptomatic at diagnosis. With multidisciplinary care teams that included dietitians, respiratory therapists, and social workers, treatment of cystic fibrosis can slow disease progression. Median survival has improved from 36.3 years (95% CI, 35.1-37.9) in 2006 to 53.1 years (95% CI, 51.6-54.7) in 2021. Pulmonary therapies for patients with cystic fibrosis consist of mucolytics (eg, dornase alfa), anti-inflammatories (eg, azithromycin), and antibiotics (such as tobramycin delivered by a nebulizer). Four small molecular therapies, termed CFTR modulators, that facilitate CFTR production and/or function have received regulatory approval. Examples are ivacaftor and elexacaftor-tezacaftor-ivacaftor. For example, in patients with 1 F508del variant, the combination of ivacaftor, tezacaftor, and elexacaftor improved lung function from −0.2% in the placebo group to 13.6% (difference, 13.8%; 95% CI, 12.1%-15.4%) and decreased the annualized estimated rate of pulmonary exacerbations from 0.98 to 0.37 (rate ratio, 0.37; 95% CI, 0.25-0.55). Improved respiratory function and symptoms have lasted up to 144 weeks in postapproval observational studies. An additional 177 variants are eligible for treatment with the elexacaftor-tezacaftor-ivacaftor combination.ConclusionCystic fibrosis affects approximately 89 000 people worldwide and is associated with a spectrum of disease related to exocrine dysfunction, including chronic respiratory bacterial infections and reduced life expectancy. First-line pulmonary therapies consist of mucolytics, anti-inflammatories, and antibiotics, and approximately 90% of people with cystic fibrosis who are 2 years or older may benefit from a combination of ivacaftor, tezacaftor, and elexacaftor.

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Section: Discussion and Observationsmentioning

confidence: 99%

Section: Practical Considerations and Application Of Evidencementioning

confidence: 99%

Cystic Fibrosis

Ong

Ramsey

2023

JAMA

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“…A prospective multi-center clinical trial called MAYFLOWERS is designed to enroll 285 pregnancies with or without CFTR modulators for a 35-month observation. This trial is expected to describe detailed outcomes in pregnancy and lactation in relation with CFTR modulators, but with, and also pre-existing, comorbid conditions 14 .…”

Section: Discussionmentioning

confidence: 99%

Pregnancy in cystic fibrosis in the era of CFTR modulators: A case series

Sionidou¹

2023

Pneumon

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“…Accordingly, a growing number of reports have been performed to assess the effects of ETI therapy on embryonic and fetal development during pregnancy and babyhood ( Table 7 ). Such information is fundamental to optimizing care for PwCF and improving the know-how in family planning and childbearing for CF women receiving ETI therapy [ 110 ].…”

Section: Clinical Outcomes Of Eti Therapy In Case Reports Observation...mentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

et al. 2023

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Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) by targeting the fundamental cause of the disease. These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). In particular, the triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide. A growing number of clinical studies have demonstrated the safety and efficacy of ETI therapy in both short- and long-term (up to two years of follow-up to date) and its ability to significantly reduce pulmonary and gastrointestinal manifestations, sweat chloride concentration, exocrine pancreatic dysfunction, and infertility/subfertility, among other disease signs and symptoms. Nevertheless, ETI therapy-related adverse effects have also been reported, and close monitoring by a multidisciplinary healthcare team remains vital. This review aims to address and discuss the major therapeutic benefits and adverse effects reported by the clinical use of ETI therapy for PwCF.

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Prospectively evaluating maternal and fetal outcomes in the era of CFTR modulators: the MAYFLOWERS observational clinical trial study design

Cited by 27 publications

References 60 publications

Cystic Fibrosis

Cystic Fibrosis

Pregnancy in cystic fibrosis in the era of CFTR modulators: A case series

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

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