Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy

Fecha de publicación: 01/04/2017

Autores de IIS La Fe

Juan Jesús Vílchez Padilla

Autor

Participantes ajenos a IIS La Fe

Buyse, GM
Voit, T
Schara, U
Straathof, CSM
D'Angelo, MG
Bernert, G
Cuisset, JM
Finkel, RS
Goemans, N
Rummey, C
Leinonen, M
Mayer, OH
Spagnolo, P
Meier, T
McDonald, CM

Grupos

Patología Neuromuscular y Ataxias

Investigador Principal

Teresa Sevilla Mantecón

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 -0.29L/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: 0.01L/sec; 95%CI: -0.22, 0.24; P=0.950). The between-group difference favoring idebenone was 0.27L/sec (P=0.043) at week 26 and 0.30L/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. (c) 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.

Datos de la publicación

ISSN/ISSNe:: 8755-6863, 1099-0496
Tipo:: Article
Páginas:: 508-515
DOI:: 10.1002/ppul.23547
Factor de Impacto:: 1,018 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Buyse, GM:: University Hospitals Leuven, Leuven, Belgium

Univ Hosp Leuven, Herestr 49, B-3000 Leuven, Belgium
Voit, T:: Institut de Myologie, UPMC INSERM UMR 974, CNRS FRE 3617, Groupe Hospitalier de la Pitié Salpêtrière, Paris, France

UPMC, Inst Myol, Grp Hosp Pitie Salpetriere, INSERM,UMR 974,CNRS,FRE 3617, Paris, France
Schara, U:: Universitätsklinikum, Essen, Germany

Univ Klinikum, Essen, Germany
Straathof, CSM:: LUMC, Leiden, Netherlands
D'Angelo, MG:: IRCCS Eugenio Medea, Lecco, Italy

IRCCS Eugenio Medea, Lecce, Italy
Bernert, G:: G.v. Preyer'sches Kinderspital, Wien, Austria

Gv Preyersches Kinderspital, Vienna, Austria
Cuisset, JM:: CHRU de Lille, Lille, France

CHRU Lille, Lille, France
Finkel, RS:: Nemours Childrens Hosp, Orlando, FL USA
Goemans, N:: University Hospitals Leuven, Leuven, Belgium

Univ Hosp Leuven, Herestr 49, B-3000 Leuven, Belgium
Rummey, C:: 4Pharma, Liestal, Switzerland
Leinonen, M:: 4Pharma, Liestal, Switzerland
Mayer, OH:: Childrens Hosp Philadelphia, Div Pulmonol, Philadelphia, PA 19104 USA
Spagnolo, P:: Santhera Pharmaceuticals, Liestal, Switzerland

Santhera Pharmaceut, Liestal, Switzerland
Meier, T:: Santhera Pharmaceuticals, Liestal, Switzerland

Santhera Pharmaceut, Liestal, Switzerland
McDonald, CM:: Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA
DELOS Study Group:: 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

IRCCS Eugenio Medea, Lecco, Italy

G.v. Preyer'sches Kinderspital, Wien, Austria

CHRU de Lille, Lille, France

4Pharma, Liestal, Switzerland

Santhera Pharmaceuticals, Liestal, Switzerland

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

Universitäts-Klinikum Freiburg, Freiburg, Germany

Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli, Napoli, Italy