The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

被引:17
作者
Abbas, Kirellos Said [1 ]
Eltaras, Mennatullah Mohamed [2 ]
El-Shahat, Nahla Ahmed [2 ]
Abdelazeem, Basel [3 ,4 ]
Shaqfeh, Mahmoud [5 ]
Brasic, James Robert [6 ]
机构
[1] Alexandria Univ, Fac Med, Alexandria 22621, Egypt
[2] Al Azhar Univ, Fac Med Girls, Cairo 11754, Egypt
[3] McLaren Hlth Care, Dept Med, Flint, MI 48532 USA
[4] Michigan State Univ, Dept Med, E Lansing, MI 48824 USA
[5] McLaren Hlth Care, Dept Neurol, Flint, MI 48532 USA
[6] Johns Hopkins Univ, Sect High Resolut Brain Positron Emiss Tomog Imag, Russell H Morgan Dept Radiol & Radiol Sci, Div Nucl Med & Mol Imaging,Sch Med, Baltimore, MD 21287 USA
来源
MEDICINA-LITHUANIA | 2022年 / 58卷 / 02期
关键词
adverse and beneficial effects; alpha motor neuron; bias; brainstem; evidence; neurodegenerative; prevalence; risk; spinal cord; survival of motor neuron 1 (SMN1) gene; SHAM CONTROL; INFANTS;
D O I
10.3390/medicina58020213
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.
引用
收藏
页数:12
相关论文
共 39 条
[1]   Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study [J].
Acsadi, Gyula ;
Crawford, Thomas O. ;
Mueller-Felber, Wolfgang ;
Shieh, Perry B. ;
Richardson, Randal ;
Natarajan, Niranjana ;
Castro, Diana ;
Ramirez-Schrempp, Daniela ;
Gambino, Giulia ;
Sun, Peng ;
Farwell, Wildon .
MUSCLE & NERVE, 2021, 63 (05) :668-677
[2]  
[Anonymous], 2014, REVMAN VERS 5 3 COMP
[3]   MOTOR MILESTONE ASSESSMENT OF INFANTS WITH SPINAL MUSCULAR ATROPHY USING THE HAMMERSMITH INFANT NEUROLOGICAL EXAM-PART 2: EXPERIENCE FROM A NUSINERSEN CLINICAL STUDY [J].
Bishop, Kathie M. ;
Montes, Jacqueline ;
Finkel, Richard S. .
MUSCLE & NERVE, 2018, 57 (01) :142-146
[4]   Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases [J].
Butchbach, Matthew E. R. .
FRONTIERS IN MOLECULAR BIOSCIENCES, 2016, 3
[5]   Age related treatment effect in type II Spinal Muscular Atrophy pediatric patients treated with nusinersen [J].
Coratti, Giorgia ;
Pane, Marika ;
Lucibello, Simona ;
Pera, Maria Carmela ;
Pasternak, Amy ;
Montes, Jacqueline ;
Sansone, Valeria A. ;
Duong, Tina ;
Young, Sally Dunaway ;
Messina, Sonia ;
D'Amico, Adele ;
Civitello, Matthew ;
Glanzman, Allan M. ;
Bruno, Claudio ;
Salmin, Francesca ;
Tacchetti, Paola ;
Carnicella, Sara ;
Sframeli, Maria ;
Antonaci, Laura ;
Frongia, Anna Lia ;
De Vivo, Darryl C. ;
Darras, Basil T. ;
Day, John ;
Bertini, Enrico ;
Muntoni, Francesco ;
Finkel, Richard ;
Mercuri, Eugenio .
NEUROMUSCULAR DISORDERS, 2021, 31 (07) :596-602
[6]   Detection of novel mutations in the SMN Tudor domain in type ISMA patients [J].
Cuscó, I ;
Barceló, MJ ;
del Río, E ;
Baiget, M ;
Tizzano, EF .
NEUROLOGY, 2004, 63 (01) :146-149
[7]   Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study [J].
De Vivo, Darryl C. ;
Bertini, Enrico ;
Swoboda, Kathryn J. ;
Hwu, Wuh-Liang ;
Crawford, Thomas O. ;
Finkel, Richard S. ;
Kirschner, Janbernd ;
Kuntz, Nancy L. ;
Parsons, Julie A. ;
Ryan, Monique M. ;
Butterfield, Russell J. ;
Topaloglu, Haluk ;
Ben-Omran, Tawfeg ;
Sansone, Valeria A. ;
Jong, Yuh-Jyh ;
Shu, Francy ;
Staropoli, John F. ;
Kerr, Douglas ;
Sandrock, Alfred W. ;
Stebbins, Christopher ;
Petrillo, Marco ;
Braley, Gabriel ;
Johnson, Kristina ;
Foster, Richard ;
Gheuens, Sarah ;
Bhan, Ishir ;
Reyna, Sandra P. ;
Fradette, Stephanie ;
Farwell, Wildon .
NEUROMUSCULAR DISORDERS, 2019, 29 (11) :842-856
[8]   Bias in meta-analysis detected by a simple, graphical test [J].
Egger, M ;
Smith, GD ;
Schneider, M ;
Minder, C .
BMJ-BRITISH MEDICAL JOURNAL, 1997, 315 (7109) :629-634
[9]   The Genetics of Spinal Muscular Atrophy: Progress and Challenges [J].
Farrar, Michelle A. ;
Kiernan, Matthew C. .
NEUROTHERAPEUTICS, 2015, 12 (02) :290-302
[10]   Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy [J].
Finkel, R. S. ;
Mercuri, E. ;
Darras, B. T. ;
Connolly, A. M. ;
Kuntz, N. L. ;
Kirschner, J. ;
Chiriboga, C. A. ;
Saito, K. ;
Servais, L. ;
Tizzano, E. ;
Topaloglu, H. ;
Tulinius, M. ;
Montes, J. ;
Glanzman, A. M. ;
Bishop, K. ;
Zhong, Z. J. ;
Gheuens, S. ;
Bennett, C. F. ;
Schneider, E. ;
Farwell, W. ;
De Vivo, D. C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (18) :1723-1732