Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland

Rüsch, Christina T.; Baumann, Dominique; Enzmann, Cornelia; Hasselmann, Oswald; Jacquier, David; Jung, Hans H.; Klein, Andrea; Kruijshaar, Michelle E.; Kuehni, Claudia E.; Lötscher, Nadine; Neuwirth, Christoph; Ramelli, Gian Paolo; Ripellino, Paolo; Scheidegger, Oliver; Stettner, Georg M.; Tscherter, Anne

doi:10.1016/j.nmd.2022.02.001

Cited by 15 publications

(14 citation statements)

References 48 publications

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“…Regardless of effective pharmacological treatment and gene therapy, children with SMA are functioning higher and the correlation with gene copy number seems to be no longer as significant as once thought. We observed in the literature that this lines up with the findings of Pane et al, Pechmann et al and Tscherter: they did not find a correlation between the SMN2 copy number and motor improvement [ 29 , 35 , 36 ]. In addition, this study is not about describing the clinical condition but only the functional changes.…”

Section: Discussionsupporting

confidence: 89%

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Prospective Analysis of Functional and Structural Changes in Patients with Spinal Muscular Atrophy—A Pilot Study

2022

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Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular disease. Recent years have seen a significant development of therapeutic options for SMA patients. With the development of treatment methods, it has become necessary to adapt a physiotherapeutic approach to the evolving clinical picture of SMA patients. We presented an analysis of 40 SMA patients undergoing pharmacological treatment, examined twice in an average interval of 5 months. Twelve patients (non-sitters) were evaluated using CHOP-INTEND, while 28 (sitters) were tested using the Hammersmith scale. The research protocol consisted of measurements of upper and lower limb ranges of motion, and four tests for early detection of musculoskeletal changes. Both non-sitters and sitters patients showed motor improvement between the first and second examinations. Favorable changes in range of motion parameters were noted in most children, except for hip extension (HE) range, which deteriorated. An association was also observed between scale scores and the presence of contractures in the hip and knee joints depending on the group studied. Our findings showed that the presence of contractures at the hip and knee joint negatively affected functional improvement as measured by the scale scores.

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Section: Discussionsupporting

confidence: 89%

“…It is worth observing that our patients with the highest improvement who were described above were diagnosed and treated in their first months of life. This is supported by the publication of Tscherter et al, where the authors underline that the best improvement results were observed in patients treated before this age [ 35 ].…”

Section: Discussionmentioning

confidence: 61%

Prospective Analysis of Functional and Structural Changes in Patients with Spinal Muscular Atrophy—A Pilot Study

2022

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“…This registry is hosted at the Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland, and was approved by the Cantonal Ethics Committee of Bern (20.06.2018, KEK Bern, 2018-00289). Procedures of data collection and processing was described previously [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…In Switzerland, nusinersen was approved for the treatment of SMA in September 2017. An evaluation of real-life outcome data of SMA patients treated with nusinersen in Switzerland was published recently using data which was prospectively collected by the Swiss Registry for Neuromuscular Disorders (Swiss-Reg-NMD) [ 15 ]. Risdiplam, a different SMN2 gene splice site modifier, was approved for the treatment of SMA in Switzerland in May 2021.…”

Section: Introductionmentioning

confidence: 99%

Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study

Stettner

Hasselmann²,

Tscherter

et al. 2023

BMC Neurol

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Background Spinal muscular atrophy (SMA) is a rare neuromuscular disorder leading to early death in the majority of affected individuals without treatment. Recently, targeted treatment approaches including Onasemnogene Abeparvovec (OA) were introduced. This study describes the first real-world experience with OA in Switzerland. Methods Prospective observational case series study using data collected within the Swiss Registry for Neuromuscular Disorders from SMA patients treated with OA. Development of motor, bulbar and respiratory function, appearance of scoliosis, and safety data (platelet count, liver function, and cardiotoxicity) were analyzed. Results Nine individuals were treated with OA and followed for 383 ± 126 days: six SMA type 1 (of which two with nusinersen pretreatment), one SMA type 2, and two pre-symptomatic individuals. In SMA type 1, CHOP Intend score increased by 28.1 from a mean score of 20.5 ± 7.6 at baseline. At end of follow-up, 50% of SMA type 1 patients required nutritional support and 17% night-time ventilation; 67% developed scoliosis. The SMA type 2 patient and two pre-symptomatically treated individuals reached maximum CHOP Intend scores. No patient required adaptation of the concomitant prednisolone treatment, although transient decrease of platelet count and increase of transaminases were observed in all patients. Troponin-T was elevated prior to OA treatment in 100% and showed fluctuations in 57% thereafter. Conclusions OA is a potent treatment for SMA leading to significant motor function improvements. However, the need for respiratory and especially nutritional support as well as the development of scoliosis must be thoroughly evaluated in SMA type 1 patients even in the short term after OA treatment.

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“…16 could sit at 12 months, and further 6 at 24 months. Tscherter et al 116 P 11; mean 1.4 years (range 0.1–16.1) CI; median 25 points (range 2–29) Median +25 points (range 2–42), median treatment duration 2.1 years. NS 5 with 2 SMN2 copies, 4 with 3 copies, 2 unknowns .…”

Section: Nusinersenmentioning

confidence: 99%

Disease Modifying Therapies for the Management of Children with Spinal Muscular Atrophy (5q SMA): An Update on the Emerging Evidence

Hjartarson¹,

Nathorst-Böös²,

Sejersen³

2022

DDDT

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SMA (5q SMA) is an autosomal recessive neuromuscular disease with an estimated incidence of approximately 1 in 11,000 live births, characterized by progressive degeneration and loss of α-motor neurons in the spinal cord and brain stem, resulting in progressive muscle weakness. The disease spectrum is wide, from a serious congenital to a mild adult-onset disease. SMA is caused by biallelic mutations in the SMN1 gene and disease severity is modified primarily by SMN2 copy number. Before the advent of specific disease altering treatments, SMA was the second most common fatal autosomal recessive disorder after cystic fibrosis and the most common genetic cause of infant mortality. Nusinersen, risdiplam, and onasemnogene abeparvovec are presently the only approved disease modifying therapies for SMA, and the aim of this review is to discuss their mode of action, effects, safety concerns, and results from real-world experience. All exert their action by increasing the level of SMN protein in lower motor neuron. Nusinersen and risdiplam by modifying the SMN2 gene product, and onasemnogene abeparvovec by delivering SMN1 gene copies into cells. All have an established clinical efficacy. An important feature shared by all three is that early intervention is associated with a better treatment outcome, such that in cases where treatment is initiated in an early pre-symptomatic period, it may result in normal – or almost normal – motor development. Thus, early diagnosis followed by swift initiation of treatment is fundamental for the treatment response and consequently long-term prognosis in SMA type 1, and probably SMA type 2. The same principle similarly applies to the milder phenotypes. All three therapies are relatively novel, with risdiplam being the latest addition. Except for nusinersen, real-world data are still scarce, and long-term data are quite naturally lacking.

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Evaluation of real-life outcome data of patients with spinal muscular atrophy treated with nusinersen in Switzerland

Cited by 15 publications

References 48 publications

Prospective Analysis of Functional and Structural Changes in Patients with Spinal Muscular Atrophy—A Pilot Study

Prospective Analysis of Functional and Structural Changes in Patients with Spinal Muscular Atrophy—A Pilot Study

Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study

Disease Modifying Therapies for the Management of Children with Spinal Muscular Atrophy (5q SMA): An Update on the Emerging Evidence

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