Therapies that are available and under development for Duchenne muscular dystrophy: What about lung function?

Abstract

Background Respiratory failure is the principal source of morbidity and mortality among patients with Duchenne muscular dystrophy exerting a negative influence on their total quality of life. The aim of this review is to provide systematically current literature evidence about the effects of different treatment options (available or under development) for Duchenne muscular dystrophy on the pulmonary function of these patients. Methods A comprehensive search was undertaken using multiple health‐related databases, while two independent reviewers assessed the eligibility of studies. A third person addressed any disagreements between reviewers. The quality of the methodology of the included studies was also assessed. Results A total of 19 original research papers (nine evaluating the role of steroids, six idebenone, three eteplirsen, one stem‐cell therapy, and one ataluren) were found to fulfill our selection criteria with the majority of them (14 of 19) being prospective studies, not always including a control group. Endpoints mainly used in these studies were values of pulmonary function tests. Current and under development treatments proved to be safe and no significant adverse events were reported. A beneficial impact on pulmonary function was described by authors in the majority of these studies. The principal effect was slowing of lung disease progress, as expressed by spirometric values. However, the risk of bias was introduced in many of the above studies, while high heterogeneity in terms of treatment protocols and outcome measures limits the comparability of the results. Conclusion Glucocorticoids remain the best‐studied pharmacologic therapy for Duchenne muscular dystrophy and very likely delay the expected decline in lung function. With regard to new therapeutic agents, initial study results are encouraging. However, larger clinical trials are needed that minimize the risk of study bias, optimize the comparability of treatment groups, examine clinically meaningful pulmonary outcome measures, and include long‐term follow up.

Cochrane's risk of bias tool for non-randomized studies (ROBINS-I) is frequently misapplied: A methodological systematic review

“…Most reviews used the seven bias domains listed in the tool. In five reviews, one domain was omitted or reported as ‘not applicable’ (domain 3, ‘classification of interventions’ [27] or 4, ‘deviations from intended interventions’ [28] , [29] , [30] , [31] ). One review used all seven domains, but added an eighth domain (‘vested interest bias’) [32] .…”

“…Most reviews used the seven bias domains listed in the tool. In five reviews, one domain was omitted or reported as ‗not applicable' (domain 3, ‗classification of interventions' [27] or 4, ‗deviations from intended interventions' [28][29][30][31]). One review used all seven domains, but added an eighth domain (‗vested interest bias') [32] One review appeared to use the seven ROBINS-I domains, but reported the results alongside results from the Cochrane RoB tool for RCTs, with domains renamed to fit both tools.…”

Clinical Profile and Pulmonary Function of Pediatric Patients with Duchenne Muscular Dystrophy at a Tertiary Government Hospital

“…Although there is no definitive cure for DMD, the use of corticosteroids has been shown to improve respiratory muscle strength and delay the expected decline in lung function by decreasing inflammation-induced muscle damage. 31,[40][41][42] Thirty percent of our patients had history of taking corticosteroids, while the mean age of commencement of corticosteroids before and upon enrollment to the multidisciplinary clinic was 9 (±2.5) years. Research on the impact of corticosteroids in our patients is recommended in a more extended study period.…”

Correlação da função motora e respiratória de indivíduos com distrofia muscular de Duchenne

“…A fisiopatologia da DMD tem muitos aspectos e as principais causas de deficiência respiratória incluem disfunção da mecânica respiratória e doença do parênquima pulmonar (aspiração crônica ou pneumonia). Sendo assim, a capacidade de sustentar ventilação depende de um equilíbrio entre o desempenho dos músculos respiratórios e a carga respiratória (Gogou et al, 2020).…”