Nusinersen versus Sham Control in Infantile‐Onset Spinal Muscular Atrophy

@article{Finkel2017NusinersenVS,
  title={Nusinersen versus Sham Control in Infantile‐Onset Spinal Muscular Atrophy},
  author={Richard S. Finkel and Eugenio Mercuri and Basil T. Darras and Anne M. Connolly and Nancy Kuntz and Janbernd Kirschner and Claudia A. Chiriboga and Kayoko Saito and Laurent Servais and Eduardo F Tizzano and Haluk A Topaloglu and M{\'a}r H. Tulinius and Jacqueline Montes and Allan M. Glanzman and Kathie M. Bishop and Z John Zhong and S. Gheuens and C. Frank Bennett and Eugene Schneider and Wildon R. Farwell and Darryl C De Vivo},
  journal={The New England Journal of Medicine},
  year={2017},
  volume={377},
  pages={1723–1732}
}
Background Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre–messenger RNA splicing of the SMN2 gene and thus promotes increased production of full‐length SMN protein. Methods We conducted a randomized, double‐blind, sham‐controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The… Expand

Paper Mentions

Observational Clinical Trial
This is a longitudinal, observational study of adult patients with genetically confirmed chromosome 5q SMA to examine the safety, tolerability, and effectiveness of SPINRAZA… Expand
ConditionsSpinal Muscular Atrophy, Spinal Muscular Atrophy Type 3, Spinal Muscular Atrophy Type II
InterventionOther
Observational Clinical Trial
Observational study of adult patients with spinal muscular atrophy types 2 and 3 receiving nusinersen  
ConditionsAdult Spinal Muscular Atrophy
InterventionDrug
Observational Clinical Trial
Early Check provides voluntary screening of newborns for a selected panel of conditions. The study has three main objectives: 1) develop and implement an approach to identify affected… Expand
ConditionsDuchenne Muscular Dystrophy, Fragile X - Premutation, Fragile X Syndrome, (+1 more)
InterventionDiagnostic Test
Interventional Clinical Trial
Intrathecal administration of Nusinersen, an antisense oligonucleotide capable of increasing Survival Motor Neuron protein production, has been tested in Spinal Muscular Atrophy (SMA… Expand
ConditionsMuscular Atrophy, Spinal, Ultrasound
InterventionDevice
Nusinersen versus Sham Control in Later‐Onset Spinal Muscular Atrophy
TLDR
Among children with later‐onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. Expand
Cost effectiveness of nusinersen for patients with infantile-onset spinal muscular atrophy in US
TLDR
The estimated incremental cost-effectiveness of nusinersen from a US health care sector perspective exceeded traditional cost-effective thresholds and was most sensitive to the length of survival, background health care costs, and utility in the “not sitting” and “sitting” health states. Expand
Current evidence for treatment with nusinersen for spinal muscular atrophy: a systematic review
Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for thisExpand
Current evidence for treatment with nusinersen for spinal muscular atrophy: a systematic review
TLDR
Results are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Expand
Effect of Nusinersen in a late onset spinal muscular atrophy patient for 14 months
TLDR
A 13-year-old boy who was diagnosed as SMA with progressive proximal limb weakness was treated with intrathecal injection of Nusinersen and showed significant clinical improvement in the revised Hammersmith functional rating scale and 6-minute walk test. Expand
Nusinersen: A Review in 5q Spinal Muscular Atrophy
TLDR
Current evidence indicates that nusinersen modifies 5q SMA and has a favourable safety profile and, thus, is a valuable treatment for this patient population. Expand
Nusinersen for Spinal Muscular Atrophy in the United States: Findings From a Retrospective Claims Database Analysis
TLDR
Analysis of claims data indicated that discontinuation and non-adherence to nusinersen treatment were prevalent, and associated with greater frequency of comorbidities, greater HCRU, and increased costs for patients. Expand
Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps
TLDR
Nusinersen represents the first efficacious marked approved drug in type 1 and type 2 SMA, and prolongs survival of patients with type 1 SMA and allows motor milestone acquisition. Expand
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TLDR
Long-term results from phase 1b/2a studies were recently published, confirming that benefit from nusinersen treatment for almost 3 years was associated with sustained improvement in motor function as well as stabilization of disease activity that is distinct from what is observed in natural history data. Expand
Respiratory outcomes post nusinersen in spinal muscular atrophy type 1
TLDR
A phase‐3 randomized, double‐blinded, sham‐controlled clinical trial in patients with SMA1 showed that those treated with nusinersen had a significant motor milestone response with a higher likelihood of event‐free survival, leaving unanswered questions about the effect of the medication on respiratory morbidity. Expand
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