Evaluation of risdiplam efficacy in 5q spinal muscular atrophy: A systematic comparison of electrophysiologic with clinical outcome measures

Kessler, Tobias; Sam, Georges; Wick, Wolfgang; Weiler, Markus

doi:10.1111/ene.16099

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…Concerning risdiplam, no clinical trials in adult patients have been conducted, although published clinical trials of risdiplam have included some adult patients [ 22 ]. In a monocentric longitudinal cohort study, HFMSE and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores increased in parallel with increases of CMAP amplitudes in both median nerves in 18 adult patients with SMA type 2 or 3 treated with risdiplam during a 10-month treatment period [ 23 ]. Observational studies, meta-analysis and real life will likely define its therapeutic effect in adult patients [ 24 – 26 ].…”

Section: Discussionmentioning

confidence: 99%

Multidisciplinary team meetings in treatment of spinal muscular atrophy adult patients: a real-life observatory for innovative treatments

Salort-Campana,

Solé,

Magot

et al. 2024

Orphanet J Rare Dis

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Background In 2017, a new treatment by nusinersen, an antisense oligonucleotide delivered by repeated intrathecal injections, became available for patients with spinal muscular atrophy (SMA), whereas clinical trials had mainly involved children. Since 2020, the oral, selective SMN2-splicing modifier risdiplam has been available with restrictions evolving with time. In this peculiar context of lack of data regarding adult patients, many questions were raised to define the indications of treatment and the appropriate follow-up in this population. To homogenize access to treatment in France, a national multidisciplinary team meeting dedicated to adult SMA patients, named SMA multidisciplinary team meeting, (SMDTs) was created in 2018. Our objective was to analyze the value of SMDTs in the decision-making process in SMA adult patients and to provide guidelines about treatment. Methods From October 2020 to September 2021, data extracted from the SMDT reports were collected. The primary outcome was the percentage of cases in which recommendations on validating treatment plans were given. The secondary outcomes were type of treatment requested, description of expectations regarding treatment and description of recommendations or follow-up and discontinuation. Data were analyzed using descriptive statistics. Comparisons between the type of treatment requested were performed using Mann–Whitney test or the Student t test for quantitative data and the Fisher’s exact test or the χ2 test for qualitative data. Results Cases of 107 patients were discussed at the SMDTs with a mean age of 35.3 (16–62). Forty-seven were SMA type 2, and 57 SMA type 3. Twelve cases were presented twice. Out of 122 presentations to the SMDTs, most of requests related to the initiation of a treatment (nusinersen (n = 46), risdiplam (n = 54), treatment without mentioning preferred choice (n = 5)) or a switch of treatment (n = 12). Risdiplam requests concerned significantly older patients (p = 0.002), mostly SMA type 2 (p < 0.0001), with greater disease severity in terms of motor and respiratory function compared to requests for nusinersen. In the year prior to presentation to the SMDTs, most of the patients experienced worsening of motor weakness assessed by functional tests as MFM32 or other meaningful scales for the most severe patients. Only 12% of the patients discussed had a stable condition. Only 49/122 patients (40.1%) expressed clear expectations regarding treatment. The treatment requested was approved by the SMDTs in 72 patients (67.2%). The most common reasons to decline treatment were lack of objective data on the disease course prior discussion to the SMDTs or inappropriate patient’s expectations. Treatment requests were more likely to be validated by the SMDTs if sufficient pre-therapeutic functional assessment had been performed to assess the natural history (55% vs. 32%) and if the patient had worsening rather than stable motor function (p = 0.029). In patients with approved treatment, a-priori criteria to define a further ineffectiveness of treatment (usually after 14 months of treatment) were proposed for 67/72 patients. Conclusions In the context of costly treatments with few controlled studies in adults with SMA, in whom assessment of efficacy can be complex, SMDTs are ‘real-world observatories’ of great interest to establish national recommendations about indications of treatment and follow-up.

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Section: Discussionmentioning

confidence: 99%

Multidisciplinary team meetings in treatment of spinal muscular atrophy adult patients: a real-life observatory for innovative treatments

Salort-Campana,

Solé,

Magot

et al. 2024

Orphanet J Rare Dis

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“…In SMA, the alpha motor neurons of the spinal cord are genetically affected, resulting in progressive muscle weakness and the development of muscle atrophy. It has been shown that 18 months of nusinersen treatment in children dramatically increases the number of motor neurons [25], and 10 months of risdiplam treatment in adult patients increases the active motor unit pool [26].…”

Section: Purpose and Hypothesis Of The Studymentioning

confidence: 99%

Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

Moshonkina,

Novikov,

Maldova

et al. 2024

Preprint

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Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

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“…In SMA, the alpha motor neurons of the spinal cord are genetically affected, resulting in progressive muscle weakness and the development of muscle atrophy. It has been shown that 18 months of nusinersen treatment in children dramatically increases the number of motor neurons [ 26 ], and 10 months of risdiplam treatment in adult patients increases the active motor unit pool [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

Novikov,

Maldova,

Shamantseva

et al. 2024

Biomedicines

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Spinal muscular atrophy (SMA) is an orphan disease characterized by the progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in this study. The median duration of drug treatment was over 20 months. The application of tSCS was performed during physical therapy for 20–40 min per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, and forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both type 2 and 3 SMA participants. The magnitude of functional changes was not associated with participant age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation on SMA.

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Evaluation of risdiplam efficacy in 5q spinal muscular atrophy: A systematic comparison of electrophysiologic with clinical outcome measures

Cited by 6 publications

References 35 publications

Multidisciplinary team meetings in treatment of spinal muscular atrophy adult patients: a real-life observatory for innovative treatments

Multidisciplinary team meetings in treatment of spinal muscular atrophy adult patients: a real-life observatory for innovative treatments

Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

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