Details

Autor(en) / Beteiligte

• Baker, Elizabeth
• Harris, William T.
• Rowe, Steven M.
• Rutland, Sarah B.
• Oates, Gabriela R.

Titel

Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis

Ist Teil von

• Journal of cystic fibrosis, 2021-07, Vol.20 (4), p.612-617

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• •Among individuals with CF aged 12–20 years who were not exposed to tobacco smoke, use of tezacaftor/ivacaftor was associated with 1.2%–1.7% improvement in ppFEV1.•Among smoke-exposed counterparts, tezacaftor/ivacaftor use was not associated with ppFEV1 improvement.•Tobacco smoke exposure nullifies the therapeutic benefit of tezacaftor/ivacaftor among individuals with CF aged 12–20 years old.•To maximize the therapeutic opportunity of CFTR modulators, every effort should be taken to eliminate tobacco smoke exposure in CF. Tobacco smoke exposure reduces CFTR functional expression in vitro and contributes to acquired CFTR dysfunction. We investigated whether it also inhibits the clinical benefit of CFTR modulators, focusing on tezacaftor/ivacaftor, approved in February 2018 for individuals with CF age ≥12 years. A retrospective longitudinal analysis of encounter-based data from the CF Foundation Patient Registry (2016–2018) compared the slope of change in lung function (GLI FEV1% predicted) before and after tezacaftor/ivacaftor initiation in smoke-exposed vs unexposed age-eligible pediatric patients. Tobacco smoke exposure (Ever/Never) was determined from caregiver self-report. Statistical analyses used hierarchical linear mixed modeling and fixed effects regression modeling. The sample included 6,653 individuals with a total of 105,539 person-period observations. Tezacaftor/ivacaftor was prescribed to 19% (1,251) of individuals, mean age 17 years, mean baseline ppFEV1 83%, 28% smoke-exposed. Tezacaftor/ivacaftor users who were smoke-exposed had a lower baseline ppFEV1 and experienced a greater lung function decline. Over two years, the difference in ppFEV1 by smoke exposure among tezacaftor/ivacaftor users increased by 1.2% (7.6% to 8.8%, p<0.001). In both mixed effects and fixed effects regression models, tezacaftor/ivacaftor use was associated with improved ppFEV1 among unexposed individuals (1.2% and 1.7%, respectively; p<0.001 for both) but provided no benefit among smoke-exposed counterparts (0.3%, p = 0.5 and 0.6%, p = 0.07, respectively). Tobacco smoke exposure nullifies the therapeutic benefit of tezacaftor/ivacaftor among individuals with CF aged 12–20 years old. To maximize the therapeutic opportunity of CFTR modulators, every effort must be taken to eliminate smoke exposure in CF.