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Triple Therapy for Cystic Fibrosis Phe508del –Gating and –Residual Function Genotypes
- Source :
- New England Journal of Medicine, New England Journal of Medicine, Massachusetts Medical Society, 2021, 385 (9), pp.815-825. ⟨10.1056/NEJMoa2100665⟩, N Engl J Med
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- BACKGROUND: Elexacaftor–tezacaftor–ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor–ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear. METHODS: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and Phe508del–gating or Phe508del–residual function genotypes. After a 4-week run-in period with ivacaftor or tezacaftor–ivacaftor, patients were randomly assigned to receive elexacaftor–tezacaftor–ivacaftor or active control for 8 weeks. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV(1)) from baseline through week 8 in the elexacaftor–tezacaftor–ivacaftor group. RESULTS: After the run-in period, 132 patients received elexacaftor–tezacaftor–ivacaftor and 126 received active control. Elexacaftor–tezacaftor–ivacaftor resulted in a percentage of predicted FEV(1) that was higher by 3.7 percentage points (95% confidence interval [CI], 2.8 to 4.6) relative to baseline and higher by 3.5 percentage points (95% CI, 2.2 to 4.7) relative to active control and a sweat chloride concentration that was lower by 22.3 mmol per liter (95% CI, 20.2 to 24.5) relative to baseline and lower by 23.1 mmol per liter (95% CI, 20.1 to 26.1) relative to active control (P
- Subjects :
- Male
[SDV]Life Sciences [q-bio]
Medizin
Gating
Cystic fibrosis
Gastroenterology
0302 clinical medicine
Genotype
030212 general & internal medicine
Child
biology
General Medicine
respiratory system
Cystic fibrosis transmembrane conductance regulator
3. Good health
Drug Combinations
Chlorides/analysis
Indoles/adverse effects
Female
Benzodioxoles/adverse effects
Adult
Pulmonary and Respiratory Medicine
medicine.medical_specialty
2019-20 coronavirus outbreak
congenital, hereditary, and neonatal diseases and abnormalities
Adolescent
Chloride Channel Agonists/adverse effects
Aminophenols/adverse effects
Sweat/chemistry
Article
03 medical and health sciences
Double-Blind Method
Pyrazoles/adverse effects
Internal medicine
medicine
Humans
In patient
Pyridines/adverse effects
Quinolines/adverse effects
business.industry
medicine.disease
respiratory tract diseases
Regimen
030228 respiratory system
biology.protein
Cystic Fibrosis Transmembrane Conductance Regulator/genetics
Cystic Fibrosis/drug therapy
business
Function (biology)
Subjects
Details
- Language :
- English
- ISSN :
- 00284793 and 15334406
- Database :
- OpenAIRE
- Journal :
- New England Journal of Medicine, New England Journal of Medicine, Massachusetts Medical Society, 2021, 385 (9), pp.815-825. ⟨10.1056/NEJMoa2100665⟩, N Engl J Med
- Accession number :
- edsair.doi.dedup.....2d49a389d697896fcc9784fdccd67e9e