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Observational Study
. 2021 Mar;20(2):213-219.
doi: 10.1016/j.jcf.2020.11.008. Epub 2020 Nov 25.

Long term clinical effectiveness of ivacaftor in people with the G551D CFTR mutation

J S Guimbellot  1 , A Baines  2 , A Paynter  2 , S L Heltshe  3 , J VanDalfsen  2 , M Jain  4 , S M Rowe  5 , S D Sagel  6 ; GOAL-e2 Investigators
Affiliations
Observational Study

Long term clinical effectiveness of ivacaftor in people with the G551D CFTR mutation

J S Guimbellot et al. J Cyst Fibros. 2021 Mar.

Abstract

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, ivacaftor, was first approved for people with CF and the G551D CFTR mutation. This study describes the long-term clinical effectiveness of ivacaftor in this population.

Methods: We conducted a multicenter, prospective, longitudinal, observational study of people with CF ages ≥6 years with at least one copy of the G551D CFTR mutation. Measurements of lung function, growth, quality of life, and sweat chloride were performed after ivacaftor initiation (baseline, 1 month, 3 months, 6 months, and annually thereafter until 5.5 years).

Results: Ninety-six participants were enrolled, with 81% completing all study measures through 5.5 years. This cohort experienced significant improvements in percent predicted forced expiratory volume in 1 second (ppFEV1) of 4.8 [2.6, 7.1] (p < 0.001) at 1.5 years, that diminished to 0.8 [-2.0, 3.6] (p = 0.57) at 5.5 years. Adults experienced larger improvements in ppFEV1 (7.4 [3.6, 11.3], p < 0.001 at 1.5 years and 4.3 [0.6, 8.1], p = 0.02 at 5.5 years) than children (2.8 [0.1, 5.6], p = 0.04 at 1.5 years and -2.0 [-5.9, 2.0], p = 0.32 at 5.5 years). Rate of lung function decline for the overall study cohort from 1 month after ivacaftor initiation through 5.5 years was estimated to be -1.22 pp/year [-1.70, -0.73]. Significant improvements in growth, quality of life measures, sweat chloride, Pseudomonas aeruginosa detection, and pulmonary exacerbation rates requiring antimicrobial therapy persisted through five years of therapy.

Conclusions: These findings demonstrate the long-term benefits and disease modifying effects of ivacaftor in children and adults with CF and the G551D mutation.

Keywords: CFTR; Ivacaftor; Lung function; Pseudomonas aeruginosa; Quality of life; Sweat chloride.

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Conflict of interest statement

Declaration of Competing Interest SMR and MJ serve as investigators and/or consultants on the design and conduct of CF clinical trials to Vertex Pharmaceuticals, the manufacturer of ivacaftor. A.P. declares a previous (within 36 months) equity interest in AbbVie, Inc. All other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.. Clinical outcomes over 5.5 years.
Each individual participant’s results for each visit are represented by a single line. A linear spline, with a knot at 30 days,is represented by a bolded line; the solid line represents all participants, the dotted line adult participants only, and the dashed pediatric participants only. A. ppFEV1; B. BMI; C.CFQ-R Respiratory Domain score; D. Sweat chloride.
Figure 2.
Figure 2.. Rate of change over time of ppFEV1.
The annualized rate of decline was stratified by age cohort. The rate of change was calculated from the initial 1-month change (vertical dotted line) through 5.5 years. The rate of change for each group is indicated by the annotations to the right of each line.
Figure 3.
Figure 3.
Distribution of CDC weight categories at baseline and 5.5 years.
See this image and copyright information in PMC

References

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