Efficacy of Idebenone to Preserve Respiratory Function above Clinically Meaningful Thresholds for Forced Vital Capacity (FVC) in Patients with Duchenne Muscular Dystrophy.

Oscar H. Mayer, Mika Leinonen, Christian Rummey, Gunnar M. Buyse, DELOS Study Group

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.; Lancet 2015; 385 : 1748-57).
OBJECTIVE: Post-hoc analyses were conducted to assess whether treatment with idebenone could reduce the risk of patients dropping below clinically meaningful thresholds of FVC% p.
METHODS: The DELOS trial enrolled DMD patients 10-18 years of age not using glucocorticoids to receive idebenone (N = 31) or placebo (N = 33) for 12 months. Change from baseline in FVC and FVC% p was assessed by hospital spirometry and analyzed by mixed model of repeated measures and slope analysis and proportions of patients falling below clinically meaningful thresholds of FVC% p were compared.
RESULTS: The change over 1 year in FVC and FVC% p showed a consistent pattern in favor of idebenone treatment across multiple analysis methods and fewer patients in the idebenone group declined by a margin of 10% or more in FVC and FVC% p compared to placebo. There were also fewer patients in the idebenone group (15%) with a decline below FVC% p of 50% compared to the placebo group (25%) and fewer patients in the idebenone group (28%) showed a decline below FVC% p of 50% or 40% or 30% compared to the placebo group (43%).
CONCLUSIONS: These data added to the consistency and clinical meaningfulness of findings from the DELOS trial showing that idebenone can slow the loss of pulmonary function in patients with DMD.
Original languageEnglish
Pages (from-to)189-198
JournalJournal of Neuromuscular Diseases
Volume4
Issue number3
Publication statusPublished - 2017

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Duchenne Muscular Dystrophy
Vital Capacity
Placebos
idebenone
Accidental Falls
Spirometry
Standard of Care
Disease Management
Respiratory Insufficiency
Glucocorticoids
Guidelines

Keywords

  • Duchenne muscular dystrophy
  • Pulmonary function
  • forced vital capacity
  • idebenone
  • respiration

Cite this

Efficacy of Idebenone to Preserve Respiratory Function above Clinically Meaningful Thresholds for Forced Vital Capacity (FVC) in Patients with Duchenne Muscular Dystrophy. / Mayer, Oscar H.; Leinonen, Mika; Rummey, Christian; Buyse, Gunnar M.; DELOS Study Group.

In: Journal of Neuromuscular Diseases, Vol. 4, No. 3, 2017, p. 189-198.

Research output: Contribution to journalArticle

Mayer, Oscar H. ; Leinonen, Mika ; Rummey, Christian ; Buyse, Gunnar M. ; DELOS Study Group. / Efficacy of Idebenone to Preserve Respiratory Function above Clinically Meaningful Thresholds for Forced Vital Capacity (FVC) in Patients with Duchenne Muscular Dystrophy. In: Journal of Neuromuscular Diseases. 2017 ; Vol. 4, No. 3. pp. 189-198.
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title = "Efficacy of Idebenone to Preserve Respiratory Function above Clinically Meaningful Thresholds for Forced Vital Capacity (FVC) in Patients with Duchenne Muscular Dystrophy.",
abstract = "BACKGROUND: Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC{\%} p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.; Lancet 2015; 385 : 1748-57).OBJECTIVE: Post-hoc analyses were conducted to assess whether treatment with idebenone could reduce the risk of patients dropping below clinically meaningful thresholds of FVC{\%} p.METHODS: The DELOS trial enrolled DMD patients 10-18 years of age not using glucocorticoids to receive idebenone (N = 31) or placebo (N = 33) for 12 months. Change from baseline in FVC and FVC{\%} p was assessed by hospital spirometry and analyzed by mixed model of repeated measures and slope analysis and proportions of patients falling below clinically meaningful thresholds of FVC{\%} p were compared.RESULTS: The change over 1 year in FVC and FVC{\%} p showed a consistent pattern in favor of idebenone treatment across multiple analysis methods and fewer patients in the idebenone group declined by a margin of 10{\%} or more in FVC and FVC{\%} p compared to placebo. There were also fewer patients in the idebenone group (15{\%}) with a decline below FVC{\%} p of 50{\%} compared to the placebo group (25{\%}) and fewer patients in the idebenone group (28{\%}) showed a decline below FVC{\%} p of 50{\%} or 40{\%} or 30{\%} compared to the placebo group (43{\%}).CONCLUSIONS: These data added to the consistency and clinical meaningfulness of findings from the DELOS trial showing that idebenone can slow the loss of pulmonary function in patients with DMD.",
keywords = "Duchenne muscular dystrophy, Pulmonary function, forced vital capacity, idebenone, respiration",
author = "Mayer, {Oscar H.} and Mika Leinonen and Christian Rummey and Buyse, {Gunnar M.} and D'Angelo, {Maria Grazia} and Sandra Gandossini and {DELOS Study Group}",
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T1 - Efficacy of Idebenone to Preserve Respiratory Function above Clinically Meaningful Thresholds for Forced Vital Capacity (FVC) in Patients with Duchenne Muscular Dystrophy.

AU - Mayer, Oscar H.

AU - Leinonen, Mika

AU - Rummey, Christian

AU - Buyse, Gunnar M.

AU - D'Angelo, Maria Grazia

AU - Gandossini, Sandra

AU - DELOS Study Group

PY - 2017

Y1 - 2017

N2 - BACKGROUND: Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.; Lancet 2015; 385 : 1748-57).OBJECTIVE: Post-hoc analyses were conducted to assess whether treatment with idebenone could reduce the risk of patients dropping below clinically meaningful thresholds of FVC% p.METHODS: The DELOS trial enrolled DMD patients 10-18 years of age not using glucocorticoids to receive idebenone (N = 31) or placebo (N = 33) for 12 months. Change from baseline in FVC and FVC% p was assessed by hospital spirometry and analyzed by mixed model of repeated measures and slope analysis and proportions of patients falling below clinically meaningful thresholds of FVC% p were compared.RESULTS: The change over 1 year in FVC and FVC% p showed a consistent pattern in favor of idebenone treatment across multiple analysis methods and fewer patients in the idebenone group declined by a margin of 10% or more in FVC and FVC% p compared to placebo. There were also fewer patients in the idebenone group (15%) with a decline below FVC% p of 50% compared to the placebo group (25%) and fewer patients in the idebenone group (28%) showed a decline below FVC% p of 50% or 40% or 30% compared to the placebo group (43%).CONCLUSIONS: These data added to the consistency and clinical meaningfulness of findings from the DELOS trial showing that idebenone can slow the loss of pulmonary function in patients with DMD.

AB - BACKGROUND: Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.; Lancet 2015; 385 : 1748-57).OBJECTIVE: Post-hoc analyses were conducted to assess whether treatment with idebenone could reduce the risk of patients dropping below clinically meaningful thresholds of FVC% p.METHODS: The DELOS trial enrolled DMD patients 10-18 years of age not using glucocorticoids to receive idebenone (N = 31) or placebo (N = 33) for 12 months. Change from baseline in FVC and FVC% p was assessed by hospital spirometry and analyzed by mixed model of repeated measures and slope analysis and proportions of patients falling below clinically meaningful thresholds of FVC% p were compared.RESULTS: The change over 1 year in FVC and FVC% p showed a consistent pattern in favor of idebenone treatment across multiple analysis methods and fewer patients in the idebenone group declined by a margin of 10% or more in FVC and FVC% p compared to placebo. There were also fewer patients in the idebenone group (15%) with a decline below FVC% p of 50% compared to the placebo group (25%) and fewer patients in the idebenone group (28%) showed a decline below FVC% p of 50% or 40% or 30% compared to the placebo group (43%).CONCLUSIONS: These data added to the consistency and clinical meaningfulness of findings from the DELOS trial showing that idebenone can slow the loss of pulmonary function in patients with DMD.

KW - Duchenne muscular dystrophy

KW - Pulmonary function

KW - forced vital capacity

KW - idebenone

KW - respiration

M3 - Article

VL - 4

SP - 189

EP - 198

JO - Journal of Neuromuscular Diseases

JF - Journal of Neuromuscular Diseases

SN - 2214-3599

IS - 3

ER -