title: Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy.
abstract: Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10-18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by -0.29 L/sec in patients on placebo (95%CI: -0.51, -0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: -0.22, 0.24; P = 0.950). The between-group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by -3.0% among patients on placebo (between-group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD. Pediatr Pulmonol. 2017;52:508-515. © 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.
authors: University Hospitals Leuven, Leuven, Belgium.
authors: Gunnar M
authors: GM
authors: Buyse
authors: Institut de Myologie, UPMC INSERM UMR 974, CNRS FRE 3617, Groupe Hospitalier de la Pitié Salpêtrière, Paris, France.
authors: Thomas
authors: T
authors: Voit
authors: Universitätsklinikum, Essen, Germany.
authors: Ulrike
authors: U
authors: Schara
authors: LUMC, Leiden, the Netherlands.
authors: Chiara S M
authors: CS
authors: Straathof
authors: IRCCS Eugenio Medea, Lecco, Italy.
authors: Maria Grazia
authors: MG
authors: D'Angelo
authors: G.v. Preyer'sches Kinderspital, Wien, Austria.
authors: Günther
authors: G
authors: Bernert
authors: CHRU de Lille, Lille, France.
authors: Jean-Marie
authors: JM
authors: Cuisset
authors: Nemours Children's Hospital, Orlando, Florida.
authors: Richard S
authors: RS
authors: Finkel
authors: University Hospitals Leuven, Leuven, Belgium.
authors: Nathalie
authors: N
authors: Goemans
authors: 4Pharma, Liestal, Switzerland.
authors: Christian
authors: C
authors: Rummey
authors: 4Pharma, Liestal, Switzerland.
authors: Mika
authors: M
authors: Leinonen
authors: Division of Pulmonology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Oscar H
authors: OH
authors: Mayer
authors: Santhera Pharmaceuticals, Liestal, Switzerland.
authors: Paolo
authors: P
authors: Spagnolo
authors: Santhera Pharmaceuticals, Liestal, Switzerland.
authors: Thomas
authors: T
authors: Meier
authors: University of California Davis Medical Center, Sacramento, California.
authors: Craig M
authors: CM
authors: McDonald
authors: University Hospitals Leuven, Leuven, Belgium.|Institut de Myologie, UPMC INSERM UMR 974, CNRS FRE 3617, Groupe Hospitalier de la Pitié Salpêtrière, Paris, France.|Universitätsklinikum, Essen, Germany.|LUMC, Leiden, the Netherlands.|IRCCS Eugenio Medea, Lecco, Italy.|G.v. Preyer'sches Kinderspital, Wien, Austria.|CHRU de Lille, Lille, France.|Nemours Children's Hospital, Orlando, Florida.|4Pharma, Liestal, Switzerland.|Santhera Pharmaceuticals, Liestal, Switzerland.|University of California Davis Medical Center, Sacramento, California.|CHUV, Lausanne, Switzerland.|Centro Clinico Nemo, Milano, Italy.|Hospital Universitari i Politècnic La Fe de Valencia, Valencia, Spain.|Astrid Lindgren Children's Hospital, Stockholm, Sweden.|University of Texas Southwestern Medical Center, Dallas, Texas.|Seattle Children's Hospital, Seattle, Washington.|Universitäts-Klinikum Freiburg, Freiburg, Germany.|Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Napoli, Italy.
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D007321:Inspiratory Reserve Volume / Q000187:drug effects; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000503:physiopathology; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D014451:Ubiquinone; C036619:idebenone
keywords: Duchenne muscular dystrophy; idebenone; inspiratory flow; respiratory function