title: Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy.
abstract: In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10-18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated "by patient" (HR 0.33, p = 0.0187) and for "all BAEs" (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics.
authors.affiliation: University of California Davis Medical Center, Sacramento, CA, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: McDonald
authors.affiliation: Santhera Pharmaceuticals, Liestal, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meier
authors.affiliation: Institut de Myologie, UPMC INSERM UMR 974, CNRS FRE 3617, Groupe Hospitalier de la Pitié Salpêtrière, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.affiliation: Universitätsklinikum, Essen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schara
authors.affiliation: LUMC, Leiden, The Netherlands.
authors.forename: Chiara S M
authors.initials: CS
authors.lastname: Straathof
authors.affiliation: IRCCS Eugenio Medea, Lecco, Italy.
authors.forename: M Grazia
authors.initials: MG
authors.lastname: D'Angelo
authors.affiliation: G.v. Preyer'sches Kinderspital, Wien, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Bernert
authors.affiliation: CHRU de Lille, Lille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.affiliation: Nemours Children's Hospital, Orlando, FL, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finkel
authors.affiliation: University Hospitals Leuven, Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goemans
authors.affiliation: 4Pharma, Liestal, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Rummey
authors.affiliation: 4Pharma, Liestal, Switzerland.
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.affiliation: Santhera Pharmaceuticals, Liestal, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Spagnolo
authors.affiliation: University Hospitals Leuven, Leuven, Belgium. Electronic address: gunnar.buyse@uzleuven.be.
authors.forename: Gunnar M
authors.initials: GM
authors.lastname: Buyse
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D006801:Humans; D015994:Incidence; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D016016:Proportional Hazards Models; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D016896:Treatment Outcome; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D014451:Ubiquinone; C036619:idebenone
keywords: Airway infection; Duchenne muscular dystrophy; Idebenone; Respiratory function