Safety, Tolerability, and Effect of Nusinersen Treatment in Ambulatory Adults With 5q-SMA

Elsheikh, Bakri; Severyn, Steven; Zhao, Songzhu; Kline, David; Linsenmayer, Matthew; Kelly, Kristina; Tellez, Marco; Bartlett, Amy; Heintzman, Sarah; Reynolds, Jerry; Sterling, Gary; Weaver, Tristan; Rajneesh, Kiran; Kolb, Stephen J.; Arnold, W. David

doi:10.3389/fneur.2021.650535

Cited by 14 publications

(19 citation statements)

References 32 publications

(83 reference statements)

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“…In our study, no significant differences were found for 6MWT score between M0 and M2, but we found a meaningful increase of 26.4 m in the 6WMT of patients with SMA type 3. This is consistent with a study by Elsheikh et al that found a 19.49-m increase in 6WMT in ambulatory patients with SMA type 3 after 2 months of treatment with nusinersen [ 25 ]. A study in patients with SMA in Hungary also found improvement in the 6WMT after 63 days of treatment [ 16 ].…”

Section: Discussionsupporting

confidence: 93%

“…On the other hand, Jochmann et al found that HFMSE scores increased in 2 patients, remained unchanged in five patients, and decreased in one patient after 2 months of treatment among seven treated with nusinersen [ 22 ]. Our findings are consistent with those of Elsheikh B et al, in which HFMSE score showed a mean difference from baseline of 2.77 points at 2 months in 23 ambulant patients, and another study showing that the mean scores increased by 0.77 point in non-ambulatory patients [ 21 , 25 ]. Szabó et al found that HFMSE scores in SMA type 2 patients increased from baseline to 2 months after nusinersen treatment [ 16 ].…”

Section: Discussionsupporting

confidence: 93%

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Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in Western China: a retrospective study

Yang

Tao

et al. 2023

BMC Neurol

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Background Spinal muscular atrophy (SMA) is a progressive degenerative neuromuscular disease. Nusinersen, with its quick onset of action, can benefit patients early in the treatment course. However, there are currently no clinical studies regarding the improvement in motor function and nutritional status of patients after loading period treatment with nusinersen. Here, we aimed to determine the efficacy of nusinersen in improving motor function and nutritional status in children with SMA treated with nusinersen after loading period in Western China. Methods In this retrospective study, data for all pediatric patients (aged < 18 years), with genetically confirmed diagnosis of SMA who were treated with nusinersen, were collected before initiation of treatment and after 2 months of treatment. We assessed motor function using standardized scales and nutritional status of patients with SMA as well as side effects of nusinersen. Results Forty-six pediatric patients aged < 18 years were enrolled in this study. After 2 months of treatment, the motor function of patients with SMA type 1, 2, and 3 improved. The difference in Revised Upper Limb Module scores from M0 to M2 was significant in patients with SMA type 2 and 3 (P = 0.004, P = 0.042, respectively). The difference in Hammersmith Functional Motor Scale Expanded scores from M0 to M2 in patients with SMA type 2 was also significant (P = 0.000). No significant differences were found for Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP-INTEND), Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), and 6-Minute Walking Test (6MWT) scores between M0 and M2, but the scores of CHOP-INTEND, HINE-2, and 6MWT were all increased after loading period treatment. The overall improvement in nutritional status was not statistically significant. No serious adverse effects were observed. Conclusions Our study provides evidence for the efficacy and safety of nusinersen and the nutritional status of pediatric patients with SMA after the loading period treatment. Motor function of all patients improved after 2 months of loading period nusinersen treatment. Patients with a shorter disease duration showed better response to treatment. Careful surveillance of nutritional status is needed in patients with SMA.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in Western China: a retrospective study

Yang

Tao

et al. 2023

BMC Neurol

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“…found a 19.49 m increase in 6WMT in ambulatory patients with SMA 3 after two months of treatment with nusinersen [19]. A study in patients with SMA in Hungary also found improvement in the 6WMT after 63 days of treatment [12].…”

Section: Discussionmentioning

confidence: 89%

Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in western China

Yang

Tao

et al. 2022

Preprint

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Introduction: The treatment of children with spinal muscular atrophy (SMA) includes disease-modifying drugs such as nusinersen. Our aim was to summarize our experience regarding the efficacy and safety of nusinersen and nutritional status in children with SMA in western China. Methods: In this retrospective study, data from all patients with a genetically confirmed diagnosis of SMA before 18 years of age who were treated with nusinersen were collected before initiation of treatment and after 2 months of treatment. We assessed the motor function of patients with SMA using standardized scales, nutritional status and side effects of nusinersen.Results: 46 patients aged < 18 years were enrolled in this study. The patients had 2 to 3 copies of the survival motor neuron 2(SMN2) gene. After 2 months of treatment, motor function of SMA type 1, 2, and 3 improved. Children with SMA have nutritional disorders, and SMA1 patients are the most malnourished. No serious adverse effects were observed. Conclusion: Our study included patients with SMA1, SMA2, and SMA3. Motor function of all pediatric SMA patients improved after 2 months of loading period nusinersen treatment. Children with SMA, especially SMA1, are prone to malnutrition; thus, nutritional management of SMA patients should be enhanced. Our study also suggests that nusinersen is safe to use, as no major side effects requiring treatment discontinuation have been reported.

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“…The wide spectrum of clinical severity in these patients and the technical difficulty associated with performing outcome measures such as HFMSE in adults represent challenges to their wider adoption. Items of SMAFRS have been previously revised to reflect relevant conceptual domains pertaining to measurement and potential response to treatment as emphasized by the FDA 2,9,10 . The simplicity and ease of performing the modified SMAFRS make it an attractive candidate outcome measure.…”

Section: Discussionmentioning

confidence: 99%

“…Each item is scored from 0 (fully dependent) to 4 (fully independent) by the participant or caregiver, with a maximum score of 40. Feasibility, test–retest reliability, as well as construct and content validity were demonstrated 2,9,10 …”

Section: Introductionmentioning

confidence: 99%

Psychometric evaluation of modified spinal muscular atrophy functional rating scale (SMAFRS) in adult patients using Rasch analysis

et al. 2023

Self Cite

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Introduction/Aims The Spinal Muscular Atrophy Functional Rating Scale (SMAFRS) was first developed as a secondary functional outcome measure to detect changes over time in patients with spinal muscular atrophy (SMA) in clinical trials. Its modified version evaluates 10 activities of daily living. The aim of the study was to analyze modified SMAFRS data using item response theory psychometric models. Methods A total of 253 responses from 41 adult patients with ambulatory and non‐ambulatory SMA types 2, 3, and 4 were analyzed. Rasch analysis was used to explore item‐person targeting, fit statistics, category response functioning, dimensionality, and differential item functioning. Results Most items had good fitting with the exception of “toileting” and “respiratory.” There were no major floor or ceiling effects, and most items covered a good range of disability with only a negligible breech of uni‐dimensionality from eating, dressing, and respiratory items. Differential item function highlighted differences in toileting, turning, transferring, walking, and respiratory items between ambulatory and non‐ambulatory populations. Discussion Despite subtle misfitting of certain items, mainly related to respiratory and bulbar function, overall modified SMAFRS remained a psychometrically stable and unidimensional outcome measure. There were some differences in measuring properties of certain functional items between ambulatory and non‐ambulatory items that need to be taken into consideration in clinical trial design. Overall, the modified SMAFRS is a psychometrically reliable tool in assessment of adult patients with SMA.

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Safety, Tolerability, and Effect of Nusinersen Treatment in Ambulatory Adults With 5q-SMA

Cited by 14 publications

References 32 publications

Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in Western China: a retrospective study

Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in Western China: a retrospective study

Assessment of motor function and nutritional status in children with spinal muscular atrophy treated with nusinersen after loading period in western China

Psychometric evaluation of modified spinal muscular atrophy functional rating scale (SMAFRS) in adult patients using Rasch analysis

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