Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy

for the SYROS and CINRG DNHS Investigators

Research output: Contribution to journalArticle

Abstract

Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs). The objective was to assess the long-term respiratory function evolution for periods On-Idebenone compared to periods Off-Idebenone in the same patients. The mean idebenone exposure in the EAPs was 4.2 (range 2.4–6.1) years. The primary endpoint was the annual change in forced vital capacity percent of predicted (FVC%p) compared between Off-Idebenone and On-Idebenone periods. The annual rate of decline in FVC%p was reduced by approximately 50% from −7.4% (95% CI: −9.1, −5.8) for the Off-Idebenone periods to −3.8% (95% CI: −4.8, −2.8) for the On-Idebenone periods (N = 11). Similarly, annual change in peak expiratory flow percent of predicted (PEF%p) was −5.9% (95% CI: −8.0, −3.9) for the Off-Idebenone periods (N = 9) and reduced to −1.9% (95% CI: −3.2, −0.7) for the On-Idebenone periods during the EAPs. The reduced rates of decline in FVC%p and PEF%p were maintained for several years with possible beneficial effects on the rate of bronchopulmonary adverse events, time to 10% decline in FVC%p and risk of hospitalization due to respiratory cause. These long-term data provide Class IV evidence to further support the disease modifying treatment effect of idebenone previously observed in randomized, controlled trials.

Original languageEnglish (US)
JournalNeuromuscular Disorders
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Duchenne Muscular Dystrophy
Vital Capacity
idebenone
Glucocorticoids
Hospitalization
Cohort Studies
Randomized Controlled Trials
Retrospective Studies

Keywords

  • Duchenne muscular dystrophy
  • Forced vital capacity
  • Idebenone
  • Real world data
  • Respiratory function

ASJC Scopus subject areas

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

Cite this

Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy. / for the SYROS and CINRG DNHS Investigators.

In: Neuromuscular Disorders, 01.01.2019.

Research output: Contribution to journalArticle

@article{21bfa05ad92f4fc991445b0fd0159ce3,
title = "Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy",
abstract = "Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs). The objective was to assess the long-term respiratory function evolution for periods On-Idebenone compared to periods Off-Idebenone in the same patients. The mean idebenone exposure in the EAPs was 4.2 (range 2.4–6.1) years. The primary endpoint was the annual change in forced vital capacity percent of predicted (FVC{\%}p) compared between Off-Idebenone and On-Idebenone periods. The annual rate of decline in FVC{\%}p was reduced by approximately 50{\%} from −7.4{\%} (95{\%} CI: −9.1, −5.8) for the Off-Idebenone periods to −3.8{\%} (95{\%} CI: −4.8, −2.8) for the On-Idebenone periods (N = 11). Similarly, annual change in peak expiratory flow percent of predicted (PEF{\%}p) was −5.9{\%} (95{\%} CI: −8.0, −3.9) for the Off-Idebenone periods (N = 9) and reduced to −1.9{\%} (95{\%} CI: −3.2, −0.7) for the On-Idebenone periods during the EAPs. The reduced rates of decline in FVC{\%}p and PEF{\%}p were maintained for several years with possible beneficial effects on the rate of bronchopulmonary adverse events, time to 10{\%} decline in FVC{\%}p and risk of hospitalization due to respiratory cause. These long-term data provide Class IV evidence to further support the disease modifying treatment effect of idebenone previously observed in randomized, controlled trials.",
keywords = "Duchenne muscular dystrophy, Forced vital capacity, Idebenone, Real world data, Respiratory function",
author = "{for the SYROS and CINRG DNHS Investigators} and Laurent Servais and Straathof, {Chiara S.M.} and Ulrike Schara and Andrea Klein and Mika Leinonen and Shabir Hasham and Thomas Meier and {De Waele}, Liesbeth and Heather Gordish-Dressman and McDonald, {Craig M.} and Mayer, {Oscar H.} and Thomas Voit and Eugenio Mercuri and Buyse, {Gunnar M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.nmd.2019.10.008",
language = "English (US)",
journal = "Neuromuscular Disorders",
issn = "0960-8966",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy

AU - for the SYROS and CINRG DNHS Investigators

AU - Servais, Laurent

AU - Straathof, Chiara S.M.

AU - Schara, Ulrike

AU - Klein, Andrea

AU - Leinonen, Mika

AU - Hasham, Shabir

AU - Meier, Thomas

AU - De Waele, Liesbeth

AU - Gordish-Dressman, Heather

AU - McDonald, Craig M.

AU - Mayer, Oscar H.

AU - Voit, Thomas

AU - Mercuri, Eugenio

AU - Buyse, Gunnar M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs). The objective was to assess the long-term respiratory function evolution for periods On-Idebenone compared to periods Off-Idebenone in the same patients. The mean idebenone exposure in the EAPs was 4.2 (range 2.4–6.1) years. The primary endpoint was the annual change in forced vital capacity percent of predicted (FVC%p) compared between Off-Idebenone and On-Idebenone periods. The annual rate of decline in FVC%p was reduced by approximately 50% from −7.4% (95% CI: −9.1, −5.8) for the Off-Idebenone periods to −3.8% (95% CI: −4.8, −2.8) for the On-Idebenone periods (N = 11). Similarly, annual change in peak expiratory flow percent of predicted (PEF%p) was −5.9% (95% CI: −8.0, −3.9) for the Off-Idebenone periods (N = 9) and reduced to −1.9% (95% CI: −3.2, −0.7) for the On-Idebenone periods during the EAPs. The reduced rates of decline in FVC%p and PEF%p were maintained for several years with possible beneficial effects on the rate of bronchopulmonary adverse events, time to 10% decline in FVC%p and risk of hospitalization due to respiratory cause. These long-term data provide Class IV evidence to further support the disease modifying treatment effect of idebenone previously observed in randomized, controlled trials.

AB - Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs). The objective was to assess the long-term respiratory function evolution for periods On-Idebenone compared to periods Off-Idebenone in the same patients. The mean idebenone exposure in the EAPs was 4.2 (range 2.4–6.1) years. The primary endpoint was the annual change in forced vital capacity percent of predicted (FVC%p) compared between Off-Idebenone and On-Idebenone periods. The annual rate of decline in FVC%p was reduced by approximately 50% from −7.4% (95% CI: −9.1, −5.8) for the Off-Idebenone periods to −3.8% (95% CI: −4.8, −2.8) for the On-Idebenone periods (N = 11). Similarly, annual change in peak expiratory flow percent of predicted (PEF%p) was −5.9% (95% CI: −8.0, −3.9) for the Off-Idebenone periods (N = 9) and reduced to −1.9% (95% CI: −3.2, −0.7) for the On-Idebenone periods during the EAPs. The reduced rates of decline in FVC%p and PEF%p were maintained for several years with possible beneficial effects on the rate of bronchopulmonary adverse events, time to 10% decline in FVC%p and risk of hospitalization due to respiratory cause. These long-term data provide Class IV evidence to further support the disease modifying treatment effect of idebenone previously observed in randomized, controlled trials.

KW - Duchenne muscular dystrophy

KW - Forced vital capacity

KW - Idebenone

KW - Real world data

KW - Respiratory function

UR - http://www.scopus.com/inward/record.url?scp=85076526483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076526483&partnerID=8YFLogxK

U2 - 10.1016/j.nmd.2019.10.008

DO - 10.1016/j.nmd.2019.10.008

M3 - Article

C2 - 31813614

AN - SCOPUS:85076526483

JO - Neuromuscular Disorders

JF - Neuromuscular Disorders

SN - 0960-8966

ER -