Exon skipping for Duchenne muscular dystrophy: a systematic review and meta-analysis
| Autor: | Hirofumi Komaki, Yuko Shimizu-Motohashi, Terumi Murakami, En Kimura, Norio Watanabe |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Duchenne muscular dystrophy Oligonucleotides Eteplirsen lcsh:Medicine Subgroup analysis Walk Test law.invention Morpholinos 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Double-Blind Method law Internal medicine Medicine Humans Pharmacology (medical) 6-min walk test Prospectively planned meta-analysis Genetics (clinical) Drisapersen Randomized Controlled Trials as Topic Pooled estimates business.industry Research lcsh:R General Medicine Exons medicine.disease Exon skipping Real-world data Clinical trial Muscular Dystrophy Duchenne 030104 developmental biology Meta-analysis business Rare disease 030217 neurology & neurosurgery |
| Zdroj: | Orphanet Journal of Rare Diseases, Vol 13, Iss 1, Pp 1-13 (2018) Orphanet Journal of Rare Diseases |
| ISSN: | 1750-1172 4201-6037 |
| Popis: | Background Exon skipping has been considered a promising therapeutic approach for Duchenne muscular dystrophy (DMD). Eteplirsen received conditional approval in the United States in 2016. To date, no systematic reviews or meta-analyses of randomized controlled trials (RCTs) of exon skipping drugs have been published to determine the pooled estimates for the effect of exon skipping in treating DMD. Methods A systematic review and meta-analysis of double-blind RCTs comparing exon-skipping drugs with placebo in DMD was performed. Trials were identified by searching published and unpublished studies from electronically available databases and clinical trial registries through October 2017. The primary outcomes were changes in the 6-min walk test (6MWT) distance, North Star Ambulatory Assessment (NSAA) scores, and adverse events. Random-effects meta-analysis and assessment of risk of bias were performed. This systematic review was registered at PROSPERO (CRD42016037504). Results Five studies involving 322 participants were included, investigating eteplirsen in one and drisapersen in four studies. There were no changes in 6MWT distance (mean difference [MD] − 9.16, 95% confidence interval [CI] − 21.94 to 3.62) or NSAA scores (MD 1.20, 95% CI − 2.35 to 4.75) after 24 weeks of treatment in the exon-skipping group compared with placebo. Subgroup analysis for a 6 mg/kg weekly injection of drisapersen showed significant changes in the 6MWT, favoring drisapersen after 24 weeks (MD − 20.24; 95% CI − 39.59 to − 0.89). However, drisapersen resulted in a significant increase in injection site reactions (risk ratio [RR] 3.67, 95% CI 1.96 to 6.89, p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink