Triple Therapy for Cystic Fibrosis Phe508del –Gating and –Residual Function Genotypes
| العنوان: | Triple Therapy for Cystic Fibrosis Phe508del –Gating and –Residual Function Genotypes |
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| المؤلفون: | VX18-445-104 Study Group, Barry, Peter J, Mall, Marcus A, Álvarez, Antonio, Colombo, Carla, de Winter-de Groot, Karin M, Fajac, Isabelle, McBennett, Kimberly A, McKone, Edward F, Ramsey, Bonnie W, Sutharsan, Sivagurunathan, Taylor-Cousar, Jennifer L, Tullis, Elizabeth, Ahluwalia, Neil, Jun, Lucy S, Moskowitz, Samuel M, Prieto-Centurion, Valentin, Tian, Simon, Waltz, David, Xuan, Fengjuan, Zhang, Yaohua, Rowe, Steven M, Polineni, Deepika, Vanderhelst, Eef, De Wachter, Elke |
| المساهمون: | Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiotherapy, Human Physiology and Anatomy, Clinical sciences, Pneumology, Pediatrics |
| المصدر: | 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 |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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) |
| الوصف: | 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 |
| اللغة: | English |
| تدمد: | 0028-4793 1533-4406 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d49a389d697896fcc9784fdccd67e9eTest https://hal.archives-ouvertes.fr/hal-03328264Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2d49a389d697896fcc9784fdccd67e9e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00284793 15334406 |
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