Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

Thomas Meier, Thomas Voit, Ulrike Schara, Chiara S M Straathof, M. Grazia D'Angelo, Günther Bernert, Jean Marie Cuisset, Richard S. Finkel, Nathalie Goemans, Christian Rummey, Mika Leinonen, Paolo Spagnolo, Gunnar M. Buyse, G. Bernert, F. Knipp, G. M. Buyse, N. Goemans, M. van den Hauwe, T. Voit, V. DopplerT. Gidaro, J. M. Cuisset, S. Coopman, U. Schara, S. Lutz, J. Kirschner, S. Borell, M. Will, M. G. D'Angelo, E. Brighina, S. Gandossini, K. Gorni, E. Falcier, L. Politano, P. D'Ambrosio, A. Taglia, J. J G M Verschuuren, C. S M Straathof, J. J. Vílchez Padilla, N. Muelas Gómez, T. Sejersen, M. Hovmöller, P. Y. Jeannet, C. Bloetzer, S. Iannaccone, D. Castro, G. Tennekoon, R. Finkel, C. Bönnemann, C. McDonald, E. Henricson, N. Joyce, Craig M. McDonald, S. Apkon, R. C. Richardson

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)473-480
Number of pages8
JournalNeuromuscular Disorders
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2016

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Keywords

  • Airway infection
  • Duchenne muscular dystrophy
  • Idebenone
  • Respiratory function

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

Cite this

Meier, T., Voit, T., Schara, U., Straathof, C. S. M., D'Angelo, M. G., Bernert, G., Cuisset, J. M., Finkel, R. S., Goemans, N., Rummey, C., Leinonen, M., Spagnolo, P., Buyse, G. M., Bernert, G., Knipp, F., Buyse, G. M., Goemans, N., van den Hauwe, M., Voit, T., ... Richardson, R. C. (2016). Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy. Neuromuscular Disorders, 26(8), 473-480. https://doi.org/10.1016/j.nmd.2016.05.008