Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease.
Genes (Basel)
; 12(8)2021 07 29.
Article
en En
| MEDLINE
| ID: mdl-34440351
ABSTRACT
We evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the Phe508del/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the treatment. Three patients were enrolled in an ELX/TEZ/IVA managed-access program, including subjects with the highest percent predicted Forced Expiratory Volume in the 1st second (ppFEV1) < 40 in the preceding 3 months. Data were collected at baseline and after 8, 12 and 24 weeks of follow-up during treatment. All patients showed a considerable decrease of sweat chloride (i.e., meanly about 60 mmol/L as compared to baseline), relevant improvement of ppFEV1 (i.e., >8) and six-minute walk test, and an increase in body mass index after the first 8 weeks of treatment. No pulmonary exacerbations occurred during the 24 weeks of treatment and all domains of the CF Questionnaire-Revised improved. No safety concerns related to the treatment occurred. This study demonstrates the benefit from the ELX/TEZ/IVA treatment in patients with CF with the Phe508del and one unidentified CFTR variant. The preliminary ex vivo analysis of the drug response on NEC helps to predict the in vivo therapeutic endpoints.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenilalanina
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Pirazoles
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Piridinas
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Pirrolidinas
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Quinolonas
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Regulador de Conductancia de Transmembrana de Fibrosis Quística
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Fibrosis Quística
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Benzodioxoles
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Agonistas de los Canales de Cloruro
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Genotipo
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Genes (Basel)
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia