Lay Summary: Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy A Single-Site Retrospective Longitudinal Study
A Single-Site Retrospective Longitudinal Study on Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy has now been published.
The study took place at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital.
You can access the full paper here and the lay summary is below.
The paper concludes that steroids, irrespective of the regime, all significantly improved respiratory function and delayed non-invasive ventilation requirements and cardiomyopathy (as compared to boys who were steroid-naive).
Please note that this is a retrospective study, so not a specifically designed clinical trial designed to look at these parameters.
Although there appear to be differences in starting lung function between regimens and impact of particular steroids, the data refer only to cardiac/lung elements and are isolated from other positive benefits of steroids. So this paper alone should not influence decisions on steroid and steroid regimes for patients with DMD, this should always be discussed with your neuromuscular consultant.
Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy: A Single-Site Retrospective Longitudinal Study. Trucco F, Domingos J, Tay CG, Ridout D, Maresh K, Munot P, Sarkozy A, Robb S, Quinlivan R, Riley M, Burch M, Fenton M, Wallis C, Chan E, Abel F, Manzur A, Muntoni F. Chest. 2020 May 7:S0012-3692(20)30869-2
Cardiac and respiratory complications represent the most severe co-morbidities associated with DMD. In the last years, the standard of care for DMD have recommended the implementation of a more pro-active approach. As consequence, a close follow up and the early establishment of ventilatory support and early initiation cardiac medications have dramatically prolonged the life expectancy of DMD boys.
What has not been fully clarified so far is the extent of protection that corticosteroids, the standard non-genetic treatment to DMD, provide to the cardiac and respiratory system. The few existing and relatively small studies suggested that boys treated with corticosteroids (CS) had a delayed onset of cardiomyopathy and respiratory deficiency compared with boys never treated.
However, nowadays virtually no DMD children remain untreated. Therefore, in our study we were particularly interested in providing new evidences to the current clinical practice. We investigated whether the two most widely used CS regimens (daily vs intermittent administration, 10 days on/10 days off) and compounds (prednisolone, 0.75 mg per kg vs deflazacort 0.9 mg per kg) had a different impact on cardiac and respiratory function and in the requirement of ventilatory support.
We have also explored whether boys bearing mutations in various segment along the Dystrophin gene had different cardiac and/or respiratory involvement. This is important because it could be possible to predict a more or less severe cardiorespiratory progression potentially at the time of genetic diagnosis.
We have retrospectively collected and analysed the cardiac and respiratory function of 270 DMD boys followed at Dubowitz Neuromuscular Centre, Great Ormond Street Hospital and part of the Northstar network, from May 2000 to June 2017. Patients enrolled in any interventional clinical trials were excluded.
DMD boys were classified as treated with daily or intermittent CS depending upon the regimen they had been treated with for the majority of the study period. The same rule was applied to stratify boys on prednisolone or deflazacort. Boys were considered CS naïve if they had never been treated, or treated for less than one consecutive month.
At their first visit, 263 of the 270 children were ambulant. Their mean age at was 6.2±2.3 years. Sixty-six patients were treated with CS daily, 182 patients with CSs intermittent, and 22 were CS- naïve.
The respiratory function in DMD boys irrespective of the regimen, started declining at 9 years of age. Children treated with daily CS started their respiratory decline from a better lung function than those on CS intermittent. However, boys on either daily or intermittent CS had respiratory deficiency and NIV requirement at a similar age, > 2 years later than CS-naïve.
Similarly, the age at cardiomyopathy was 16.6 years in boys on CS irrespective of regimen and 13.9 years in the CS-naïve group.
Deflazacort had a shorter protective effects on respiratory function compared to prednisolone, while the protection on cardiac function was similar.
We have found that boys amenable to the skipping of exon 44 had a slower decline of respiratory function than the other boys, while no differences were found in the cardiac function. These results are in line with the fact that children amenable for exon 44 skipping are known to have a milder motor decline.
In conclusion, our study is the first that compare the impact of the two most widely used CS regimens and compound on the cardiac and respiratory function of boys with DMD. CS, irrespective of the regimen of administration, significantly improved respiratory function and delayed NIV requirement and cardiomyopathy.
London 9th of July 2020
Federica Trucco, Adnan Manzur and Francesco Muntoni, on behalf of the authors
If you have any questions, please email [email protected]
Published on 20 July 2020Share this article Categories DMD research