Susanna A McColley1, Michael W Konstan2, Bonnie W Ramsey3, J Stuart Elborn4, Michael P Boyle5, Claire E Wainwright6, David Waltz7, Montserrat Vera-Llonch8, Gautham Marigowda9, John G Jiang8, Jaime L Rubin10. 1. Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, 225 East Chicago Avenue #43, Chicago, IL 60611, USA. Electronic address: SMcColle@luriechildrens.org. 2. Case Western Reserve University School of Medicine and Rainbow Babies & Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: Michael.Konstan@UHhospitals.org. 3. Seattle Children's Hospital and University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA. Electronic address: bonnie.ramsey@seattlechildrens.org. 4. Imperial College and Royal Brompton Hospital, London and Queens University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK. Electronic address: s.elborn@qub.ac.uk. 5. Johns Hopkins Medical Institution, 600 North Wolfe Street, Baltimore, MD 21287, USA. Electronic address: mboyle@jhmi.edu. 6. Lady Cilento Children's Hospital and Child Health Research Centre, University of Queensland, 62 Graham Street, South Brisbane, Queensland 4104, Australia. Electronic address: Claire.Wainwright@health.qld.gov.au. 7. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: david_waltz@vrtx.com. 8. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. 9. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: gautham_marigowda@vrtx.com. 10. Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA 02210, USA. Electronic address: jaime_rubin@vrtx.com.
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 (ppFEV1) 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 ppFEV1 > 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.
RCT Entities:
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 (ppFEV1) 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 ppFEV1 > 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.
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