Nusinersen for older patients with spinal muscular atrophy: A real‐world clinical setting experience

Veerapandiyan, Aravindhan; Eichinger, Katy; Guntrum, Debra; Kwon, Jennifer M.; Baker, Lindsay B.; Collins, Érin; Ciafaloni, Emma

doi:10.1002/mus.26769

Cited by 56 publications

(49 citation statements)

References 13 publications

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“…Five randomized placebo controlled clinical trials and three open label trials evaluated medications (valproic acid, gabapentin, salbutamol, hydroxyurea and nusinersen) in adults with SMA type II and III (n = 362 participants, follow up 6-12 months), using different measures of muscle strength and function: four showed no statistically significant effects on the outcome measures, and an open label study of nusinersen showed mean improvement of 8.25 m in the 6 min walk test (p = 0.01), Taken together these were rated as providing Level 1-4 evidence (Table 2) on the Oxford Centre for Evidencebased Medicine scale. Seven case series reported administration of intrathecal nusinersen, with radiological guidance an option for administration, using transforaminal or interlaminar approaches +/− laminotomy [89][90][91][92][93][94][95]. Lumbar punctures were mostly well tolerated, adverse events included post lumbar headache and subarachnoid haemorrhage.…”

Section: Medicationsmentioning

confidence: 99%

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

Wan

Carey

D’Silva

et al. 2020

Orphanet J Rare Dis

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Background: Spinal muscular atrophy (SMA) is a neurodegenerative disease that has a substantial and multifaceted burden on affected adults. While advances in supportive care and therapies are rapidly reshaping the therapeutic environment, these efforts have largely centered on pediatric populations. Understanding the natural history, care pathways, and patient-reported outcomes associated with SMA in adulthood is critical to advancing health policy, practice and research across the disease spectrum. The aim of this study was to systematically review research investigating the healthcare, well-being and lived experiences of adults with SMA. Methods: In accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines, seven electronic databases were systematically searched until January 2020 for studies examining clinical (physical health, natural history, treatment) and patient-reported (symptoms, physical function, mental health, quality of life, lived experiences) outcomes in adults with SMA. Study risk of bias and the level of evidence were assessed using validated tools. Results: Ninety-five articles met eligibility criteria with clinical and methodological diversity observed across studies. A heterogeneous clinical spectrum with variability in natural history was evident in adults, yet slow declines in motor function were reported when observational periods extended beyond 2 years. There remains no high quality evidence of an efficacious drug treatment for adults. Limitations in mobility and daily activities associated with deteriorating physical health were commonly reported, alongside emotional difficulties, fatigue and a perceived lack of societal support, however there was no evidence regarding effective interventions. Conclusions: This systematic review identifies the many uncertainties regarding best clinical practice, treatment response, and long-term outcomes for adults with SMA. This comprehensive identification of the current gaps in knowledge is essential to guide future clinical research, best practice care, and advance health policy with the ultimate aim of reducing the burden associated with adult SMA.

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Section: Medicationsmentioning

confidence: 99%

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

Wan

Carey

D’Silva

et al. 2020

Orphanet J Rare Dis

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“…Pivotal trials were conducted in infants and children [4,5]. Only recently, safety and feasibility of administration in older SMA patients has been demonstrated [6,7]. First studies indicated beneficial treatment effects in adults and more data on long-term efficacy are soon to be expected [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment

et al. 2020

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Background Efficacy of nusinersen in adult 5q-spinal muscular atrophy (SMA) patients regarding motor function has recently been demonstrated. However, additional outcome measures are needed to capture non-motor improvements. Fatigue is a common and disabling symptom in neurologic diseases, but little is known about its frequency, characteristics and associated factors in SMA. Objective To characterize fatigue in SMA patients receiving nusinersen, identify associated factors and evaluate fatigue as potential patient-reported outcome measure (PRO). Methods We assessed fatigue in adults with genetically confirmed 5q-SMA in a prospective longitudinal monocentric study using the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Factors associated with fatigue including health-related quality of life (HRQOL) were evaluated. Results 75% of participants were abnormally fatigued with highest scores in the dimensions physical, followed by general fatigue and reduced activity. 53% agreed that fatigue was among their three most disabling symptoms. Reduced activity was reported more extensively by participants with ≥ 4 copies of the survival of motor neuron 2 gene and better motor function. General and mental fatigue correlated positively with age and disease duration. HRQOL was inversely correlated with physical fatigue, which was not associated with disease or participant characteristics. During 14 months of nusinersen treatment, fatigue measures remained mostly stable with a trend towards improvement in reduced activity, general and physical fatigue. Conclusion Fatigue is a frequent and relevant complaint in adult SMA patients. Fatigue should be taken into consideration as additional outcome measure, but needs further evaluation in a larger patient cohort over a longer observation period.

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“…With the continuous development of technology, some drugs have entered clinical trials and are even being marketed. The advanced biopharmaceutical company [11]. Cytokinetics was awarded CK-2127107 by the US Food and Drug Administration as an experimental drug for the treatment of spinal muscular atrophy (SMA).…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China

et al. 2020

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Background: Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA. Methods: In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019. Results: Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1~2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants. Conclusions: Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.

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Nusinersen for older patients with spinal muscular atrophy: A real‐world clinical setting experience

Cited by 56 publications

References 13 publications

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

Health, wellbeing and lived experiences of adults with SMA: a scoping systematic review

An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment

Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China

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