TY - JOUR
T1 - Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy
AU - for the DELOS Study Group
AU - Buyse, Gunnar M.
AU - Voit, Thomas
AU - Schara, Ulrike
AU - Straathof, Chiara S.M.
AU - D'Angelo, Maria Grazia
AU - Bernert, Günther
AU - Cuisset, Jean Marie
AU - Finkel, Richard S.
AU - Goemans, Nathalie
AU - Rummey, Christian
AU - Leinonen, Mika
AU - Mayer, Oscar H.
AU - Spagnolo, Paolo
AU - Meier, Thomas
AU - McDonald, Craig M.
AU - Knipp, F.
AU - Van den Hauwe, M.
AU - Doppler, V.
AU - Gidaro, T.
AU - Coopman, S.
AU - Lutz, S.
AU - Kirschner, J.
AU - Borell, S.
AU - Will, M.
AU - Brighina, E.
AU - Gandossini, S.
AU - Gorni, K.
AU - Falcier, E.
AU - Politano, L.
AU - D’Ambrosio, P.
AU - Taglia, A.
AU - Verschuuren, J. J.G.M.
AU - Vílchez Padilla, J. J.
AU - Muelas Gómez, N.
AU - Sejersen, T.
AU - Hovmöller, M.
AU - Jeannet, P. Y.
AU - Bloetzer, C.
AU - Iannaccone, S.
AU - Castro, D.
AU - Tennekoon, G.
AU - Finkel, R.
AU - Bönnemann, C.
AU - McDonald, C.
AU - Henricson, E.
AU - Joyce, N.
AU - Apkon, S.
AU - Richardson, R. C.
N1 - Publisher Copyright:
© 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
KW - Duchenne muscular dystrophy
KW - idebenone
KW - inspiratory flow
KW - respiratory function
UR - http://www.scopus.com/inward/record.url?scp=84992151830&partnerID=8YFLogxK
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U2 - 10.1002/ppul.23547
DO - 10.1002/ppul.23547
M3 - Article
C2 - 27571420
AN - SCOPUS:84992151830
SN - 8755-6863
VL - 52
SP - 508
EP - 515
JO - Pediatric pulmonology
JF - Pediatric pulmonology
IS - 4
ER -