Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV                         1

Susanna A. McColley; Michael W. Konstan; Bonnie W. Ramsey; J. Stuart Elborn; Michael P. Boyle; Claire E. Wainwright; David Waltz; Montserrat Vera-Llonch; Gautham Marigowda; John G. Jiang; Jaime L. Rubin

doi:10.1016/j.jcf.2018.07.011

Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV ₁

Susanna A. McColley^*, Michael W. Konstan, Bonnie W. Ramsey, J. Stuart Elborn, Michael P. Boyle, Claire E. Wainwright, David Waltz, Montserrat Vera-Llonch, Gautham Marigowda, John G. Jiang, Jaime L. Rubin

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement. Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV ₁ ) change from baseline to day 15 into threshold categories (absolute change ≤0 vs >0; relative change <5% vs ≥5%) and compared PEx rates vs placebo. Results: LUM (400 mg q12h)/IVA (250 mg q12h)–treated patients (n = 369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV ₁ > 0 and 0.85 for those with absolute change ≤0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40–0.69; P <.0001], 0.74 [0.55–0.99; P =.04]). Conclusions: LUM/IVA significantly reduced PEx, even in patients without early lung function improvement.

Original language	English (US)
Pages (from-to)	94-101
Number of pages	8
Journal	Journal of Cystic Fibrosis
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.jcf.2018.07.011
State	Published - Jan 2019

Funding

This work was supported by Vertex Pharmaceuticals Incorporated. The sponsor participated in the design of the study in collaboration with the authors. The sponsor performed the statistical analysis and contributed to data interpretation. Medical writing and editorial support and coordination were funded by the sponsor. This work was supported by Vertex Pharmaceuticals Incorporated. The sponsor participated in the design of the study in collaboration with the authors. The sponsor performed the statistical analysis and contributed to data interpretation. Medical writing and editorial support and coordination were funded by the sponsor.

Keywords

Cystic fibrosis
Ivacaftor
Lumacaftor
Percent predicted forced expiratory volume in 1 s
Pulmonary exacerbations

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Pulmonary and Respiratory Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jcf.2018.07.011

Cite this

McColley, S. A., Konstan, M. W., Ramsey, B. W., Stuart Elborn, J., Boyle, M. P., Wainwright, C. E., Waltz, D., Vera-Llonch, M., Marigowda, G., Jiang, J. G., & Rubin, J. L. (2019). Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV ₁ Journal of Cystic Fibrosis, 18(1), 94-101. https://doi.org/10.1016/j.jcf.2018.07.011

@article{f3ed68ae4e1a4c0e8f7f7a662838cb85,

title = " Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV 1 ",

abstract = " Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement. Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV 1 ) change from baseline to day 15 into threshold categories (absolute change ≤0 vs >0; relative change <5% vs ≥5%) and compared PEx rates vs placebo. Results: LUM (400 mg q12h)/IVA (250 mg q12h)–treated patients (n = 369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV 1 > 0 and 0.85 for those with absolute change ≤0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40–0.69; P <.0001], 0.74 [0.55–0.99; P =.04]). Conclusions: LUM/IVA significantly reduced PEx, even in patients without early lung function improvement.",

keywords = "Cystic fibrosis, Ivacaftor, Lumacaftor, Percent predicted forced expiratory volume in 1 s, Pulmonary exacerbations",

author = "McColley, {Susanna A.} and Konstan, {Michael W.} and Ramsey, {Bonnie W.} and {Stuart Elborn}, J. and Boyle, {Michael P.} and Wainwright, {Claire E.} and David Waltz and Montserrat Vera-Llonch and Gautham Marigowda and Jiang, {John G.} and Rubin, {Jaime L.}",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s)",

year = "2019",

month = jan,

doi = "10.1016/j.jcf.2018.07.011",

language = "English (US)",

volume = "18",

pages = "94--101",

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McColley, SA, Konstan, MW, Ramsey, BW, Stuart Elborn, J, Boyle, MP, Wainwright, CE, Waltz, D, Vera-Llonch, M, Marigowda, G, Jiang, JG & Rubin, JL 2019, ' Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV ₁ ', Journal of Cystic Fibrosis, vol. 18, no. 1, pp. 94-101. https://doi.org/10.1016/j.jcf.2018.07.011

Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV ₁ . / McColley, Susanna A.; Konstan, Michael W.; Ramsey, Bonnie W. et al.
In: Journal of Cystic Fibrosis, Vol. 18, No. 1, 01.2019, p. 94-101.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV 1

AU - McColley, Susanna A.

AU - Konstan, Michael W.

AU - Ramsey, Bonnie W.

AU - Stuart Elborn, J.

AU - Boyle, Michael P.

AU - Wainwright, Claire E.

AU - Waltz, David

AU - Vera-Llonch, Montserrat

AU - Marigowda, Gautham

AU - Jiang, John G.

AU - Rubin, Jaime L.

PY - 2019/1

Y1 - 2019/1

N2 - Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement. Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV 1 ) change from baseline to day 15 into threshold categories (absolute change ≤0 vs >0; relative change <5% vs ≥5%) and compared PEx rates vs placebo. Results: LUM (400 mg q12h)/IVA (250 mg q12h)–treated patients (n = 369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV 1 > 0 and 0.85 for those with absolute change ≤0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40–0.69; P <.0001], 0.74 [0.55–0.99; P =.04]). Conclusions: LUM/IVA significantly reduced PEx, even in patients without early lung function improvement.

AB - Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement. Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV 1 ) change from baseline to day 15 into threshold categories (absolute change ≤0 vs >0; relative change <5% vs ≥5%) and compared PEx rates vs placebo. Results: LUM (400 mg q12h)/IVA (250 mg q12h)–treated patients (n = 369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV 1 > 0 and 0.85 for those with absolute change ≤0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40–0.69; P <.0001], 0.74 [0.55–0.99; P =.04]). Conclusions: LUM/IVA significantly reduced PEx, even in patients without early lung function improvement.

KW - Cystic fibrosis

KW - Ivacaftor

KW - Lumacaftor

KW - Percent predicted forced expiratory volume in 1 s

KW - Pulmonary exacerbations

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McColley SA, Konstan MW, Ramsey BW, Stuart Elborn J, Boyle MP, Wainwright CE et al. Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV ₁ Journal of Cystic Fibrosis. 2019 Jan;18(1):94-101. doi: 10.1016/j.jcf.2018.07.011