Clinical Outcomes in Patients with Spinal Muscular Atrophy Type 1 Treated with Nusinersen

Mendonça, Rodrigo de Holanda; Polido, Graziela Jorge; Matsui, Ciro; Solla, Davi Jorge Fontoura; Reed, Umbertina Conti; Zanoteli, Edmar

doi:10.3233/jnd-200533

Cited by 16 publications

(31 citation statements)

References 24 publications

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“…Lavie et al and Ali et al identified no reduction in NIV needs 24 months post-treatment [ 36 , 43 ]. De Holanda Mendonca et al reported data on SMA1 patients with different duration of monitoring and it took 6–24 months to demonstrate a decrease in NIV support needs in only a minority of them [ 42 ]. Similarly, Kim et al were able to identify diminished NIV use by only two hours post-Nusinersen in 50% of a small cohort of patients, who were on NIV at baseline [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…Taking under consideration all patients treated with Nusinersen in all included studies who were receiving respiratory support at baseline, a reduction in ventilator settings was noted in only 7.5% of them and unchanged settings in 70.9% during monitoring for up to 24 months post-treatment initiation [ 32 , 36 , 38 , 39 , 40 , 42 , 43 , 44 ].…”

Section: Resultsmentioning

confidence: 99%

“…Children already on IMV via tracheostomy usually have poor response to treatment, although there may be exceptions [ 32 , 37 , 42 ]. From the included studies, it is also evident that patients with severe SMA type as well as those with low neuromuscular scores, like the Hammersmith Infant Neurological Examination Score (HINE-Score), are less likely to improve from a respiratory point of view [ 32 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

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Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

2022

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Spinal muscular atrophy (SMA) is a genetic neuromuscular disease resulting in global muscular weakness and, frequently, in respiratory failure and premature death. Gene-based therapies like Nusinersen are now available for patients with SMA. The aim of this review was to assess in “real world” studies, whether novel treatments would have a positive impact on the mechanical ventilatory support requirements of SMA patients, already initiated on ventilatory support prior to treatment administration. A literature search was performed in Pubmed using multiple combinations of MESH terms and the snowball procedure. A total of 14 publications were discussed in this review. Considering all patients included in the published studies who were on ventilatory support and were treated with Nusinersen, 13/172 (7.5%) had reduced needs for ventilatory support, 1/172 (0.6%) did not need ventilation post-treatment, and 122/172 (70.9%) were maintained on the same ventilator settings. Moreover, 2/41 (4.9%) children who were offered gene therapy had no need for further ventilatory support and 12/41 (29.2%) had reduced requirements. In conclusion, available evidence suggests that among children with SMA, who are on mechanical respiratory support either noninvasively or via tracheostomy at the time of gene-based treatment, only a few will be weaned off the ventilator or have reduced ventilator needs per 24 h. Children will usually require the same level of support as before treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

2022

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“…Nusinersen treatment has been associated with both improvement 52,[141][142][143] and no effect 144,145 on lung function in various studies measured via FVC and need for assisted ventilation. Responses to nusinersen likely differ between SMN type and timing of intervention relative to symptom onset.…”

Section: Chest Deformity Thoracic Insufficiency and Pulmonary Healthmentioning

confidence: 99%

Best Practices for the Orthopaedic Care of Children with Spinal Muscular Atrophy: A Consensus Statement from the European Neuromuscular Centre Standard of Care Orthopaedic Working Group

Vitale¹,

Roye²,

Bloom³

et al. 2022

Journal of the Pediatric Orthopaedic Society of North America

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Purpose: Spinal muscular atrophy (SMA) is a genetic disease resulting in orthopaedic problems that warrant intervention. Recent genetic therapies appear to improve the natural course of this disease, prompting care providers to rethink treatment strategies. Insufficient high-quality evidence exists to guide optimal intervention in this new landscape. To address this, the European Neuromuscular Centre (ENMC) tasked an orthopaedic subgroup to update previous recommendations. Materials and Methods: A consensus statement on orthopaedic treatment of patients with SMA undergoing genetic therapy was sought via Delphi method. After review of the orthopaedic literature, three iterative surveys were administered from 2015-2016 to worldwide experts in orthopaedic care of children with SMA. Surveys identified important topics for optimal management, solicited responses regarding management and evaluation of identified topics, and clarified decision-making strategies and indications for evaluation and management, respectively. In light of new evidence of the long-term effects of gene therapy on SMA patients, an additional review of literature was used to contextualize the consensus recommendations. Results: Thirteen experts on orthopaedic management of SMA identified treatment of spine deformity, hip instability, and joint contractures as issues of importance. Experts recommended instrumentation in spinal deformity for major curves greater than 50 degrees, while monitoring pain, respiratory function, kyphosis, pelvic obliquity, functional status, trunk imbalance, and rib deformity. Preferential use of magnetically controlled growth constructs and performance of final fusion with skipped levels to accommodate intrathecal access were also endorsed. Additionally, experts advocated for surgical correction of hip instability and/or contractures that cause pain or functional impairment. Conclusions: Practice guidelines for management of scoliosis, hip instability and joint contractures were created to aid clinical decision-making in the era of genetic therapy.

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“…The Brazilian National Health Surveillance Agency (ANVISA) approved it in 2017 7 . Because of its inability to cross the blood-brain barrier, nusinersen is administered intrathecally in a therapeutic regimen requiring four lumbar punctures within two months and consecutive maintenance injections every four months thereafter 5,6,7,8,9 . This administration schedule has proven to be a challenge in patients with scoliosis and in those with previous spinal fusion.…”

Section: Introductionmentioning

confidence: 99%

Managing intrathecal administration of nusinersen in adolescents and adults with 5q-spinal muscular atrophy and previous spinal surgery

Mendonça

Fernandes

Pinto

et al. 2021

Arq. Neuro-Psiquiatr.

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Background: Spinal muscular atrophy (SMA) is a neurodegenerative disease of lower motor neurons associated with frequent occurrence of spinal deformity. Nusinersen is an antisense oligonucleotide that increases SMN protein level and is administrated by frequent intrathecal lumbar injections. Thus, spinal deformities and previous spinal surgery are important challenges for drug delivery in SMA. Objective: To report imaging methods used for Nusinersen injection in SMA patients. Methods: Nusinersen injection procedures in SMA types 2 and 3 patients who had previous spinal surgery were analyzed retrospectively to describe the imaging and puncture procedures, as well as the occurrence of complications. Results: Nine SMA patients (14 to 50 years old) underwent 57 lumbar punctures for nusinersen injection. Six patients had no interlaminar space available; in five of them, a transforaminal approach was used, and another one underwent a surgery to open a posterior bone window for the injections. Transforaminal puncture was performed using CT scan in three cases and fluoroscopy in the other two, with a similar success rate. One patient in the transforaminal group had post-procedure radiculitis, and another one had vagal reaction (hypotension). In three cases, with preserved interlaminar space, injections were performed by posterior interlaminar puncture, and only one adverse event was reported (post-puncture headache). Conclusion: In SMA patients with previous spinal surgery, the use of imaging-guided intervention is necessary for administering intrathecal nusinersen. Transforaminal technique is indicated in patients for whom the interlaminar space is not available, and injections should always be guided by either CT or fluoroscopy.

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Clinical Outcomes in Patients with Spinal Muscular Atrophy Type 1 Treated with Nusinersen

Cited by 16 publications

References 24 publications

Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

Changes in Ventilatory Support Requirements of Spinal Muscular Atrophy (SMA) Patients Post Gene-Based Therapies

Best Practices for the Orthopaedic Care of Children with Spinal Muscular Atrophy: A Consensus Statement from the European Neuromuscular Centre Standard of Care Orthopaedic Working Group

Managing intrathecal administration of nusinersen in adolescents and adults with 5q-spinal muscular atrophy and previous spinal surgery

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