English Polski
Vol 34, No 62 (2024): Continuous Publishing
Research paper
Published online: 2025-01-24

open access

Page views 41
Article views/downloads 43
Get Citation

Connect on Social Media

Connect on Social Media

Efficacy of nusinersen treatment in type 1, 2, and 3 spinal muscular atrophy: real-world data from a single-center study

Anna Lemska1, Piotr Ruminski1, Jakub Szymarek1, Sylwia Studzinska2, Maria Mazurkiewicz-Beldzinska1
Neurol Dziec 2024;34(62):25-34.

Abstract

This article is a reprint of a paper: Lemska A., Ruminski P., Szymarek, J. et al. Efficacy of nusinersen treatment in type 1, 2, and 3 spinal muscular atrophy: real-world data from a single-center study. Neurol. Int. 2024, 16(6): 1266–1278. DOI: 10.3390/neurolint16060096. When citing this work, please refer to the original publication.   Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disease characterized by progressive muscle weakness and atrophy due to the absence of the survival motor neuron 1 (SMN1) gene. SMA is classified into types 0 through 4 based on the age of symptom onset and the severity of motor function decline. Recent advances in SMA treatment, including nusinersen, onasemnogene abeparvovec, and risdiplam, have significantly improved the prognosis of SMA patients. This study evaluated the safety and efficacy of nusinersen in pediatric patients with SMA types 1, 2, and 3 in a real-world clinical setting. Methods: This prospective observational single-center study assessed the treatment effects of nusinersen in 23 pediatric patients with genetically confirmed SMA over a 22-month observation period. All the participants received intrathecal loading doses of 12 mg of nusinersen on days 1, 14, 28, and 63, followed by maintenance doses every four months. Functional assessments were conducted using the CHOP-INTEND scale. Data were collected during routine patient visits, including clinical laboratory tests and vital sign parameters, and adverse events were recorded. The inclusion criteria were defined by the national reimbursement program for nusinersen treatment in Poland. Results: Initially, 37 patients ranging from 1 month old to 18 years old were included, but 23 were ultimately observed due to changes in treatment regimens or assessment scales. The patients showed significantly improved CHOP-INTEND scores over the 22-month period. At 6 months, the average increase was 4.2 points, continuing to 17.8 points at 22 months. By the end of the study, 100% of patients showed either stabilization or improvement, with significant clinical improvements observed in several patients. Nusinersen was generally well-tolerated, with post-lumbar puncture headache and lower back pain being the most common adverse events. Conclusions: Nusinersen treatment significantly enhances motor function in pediatric patients with SMA types 1, 2, and 3. This study demonstrates the importance of early and sustained treatment, with most patients showing the continuous improvement or stabilization of motor function. These findings support the use of nusinersen as an effective therapy for SMA; however, further research is needed to understand the long-term outcomes and optimize treatment strategies.

Article available in PDF format

View PDF Download PDF file

References

  1. Prior TW, Leach ME, Finanger E. Spinal muscular atrophy. GeneReviews, Seattle 1993: 1993–2024.
  2. Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Human Mutation. 2000; 15(3): 228–237, doi: 10.1002/(sici)1098-1004(200003)15:3<228::aid-humu3>3.0.co;2-9.
  3. Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015; 51(2): 157–167.
  4. Kolb SJ, Kissel JT. Spinal muscular atrophy. Neurol Clin. 2015; 33(4): 831–846.
  5. Calucho M, Bernal S, Alías L, et al. Correlation between SMA type and SMN2 copy number revisited: An analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuromuscul Disord. 2018; 28(3): 208–215.
  6. Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy — a literature review. Orphanet J Rare Dis. 2017; 12(1): 124.
  7. Lefebvre S, Sarret C. Pathogenesis and therapeutic targets in spinal muscular atrophy (SMA). Arch Pediatr. 2020; 27(7S): 7S3–7S8.
  8. Chen TH. New and developing therapies in spinal muscular atrophy: from genotype to phenotype to treatment and where do we stand? Int J Mol Sci. 2020; 21(9).
  9. Talbot K, Tizzano EF. The clinical landscape for SMA in a new therapeutic era. Gene Ther. 2017; 24(9): 529–533.
  10. Butchbach MER. Genomic variability in the survival motor neuron genes (SMN1 and SMN2): implications for spinal muscular atrophy phenotype and therapeutics development. Int J Mol Sci. 2021; 22(15).
  11. Ratni H, Ebeling M, Baird J, et al. Discovery of risdiplam, a selective survival of motor neuron-2 ( SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA). J Med Chem. 2018; 61(15): 6501–6517.
  12. Grotto S, Cuisset JM, Marret S, et al. Type 0 spinal muscular atrophy: further delineation of prenatal and postnatal features in 16 patients. J Neuromuscul Dis. 2016; 3(4): 487–495.
  13. The Polish National Treatment Program for Patients with Spinal Muscular Atrophy (SMA). https://www.gov.pl/web/zdrowie/obwieszczenia-ministra-zdrowia-lista-lekow-refundowanych (11.09.2024).
  14. Tiberi E, Costa S, Pane M, et al. Nusinersen in type 0 spinal muscular atrophy: should we treat? Ann Clin Transl Neurol. 2020; 7(12): 2481–2483.
  15. Glanzman AM, Mazzone E, Main M, et al. The children's hospital of philadelphia infant test of neuromuscular disorders (CHOP-INTEND): test development and reliability. Neuromuscul Disord. 2010; 20(3): 155–161.
  16. Glanzman AM, McDermott MP, Montes J, et al. Pediatric Neuromuscular Clinical Research Network for Spinal Muscular Atrophy (PNCR), Muscle Study Group (MSG). Validation of the children's hospital of philadelphia infant test of neuromuscular disorders (CHOP INTEND). Pediatr Phys Ther. 2011; 23(4): 322–326.
  17. Wadman RI, Wijngaarde CA, Stam M, et al. Muscle strength and motor function throughout life in a cross-sectional cohort of 180 patients with spinal muscular atrophy types 1c-4. Eur J Neurol. 2018; 25(3): 512–518.
  18. Annoussamy M, Seferian AM, Daron A, et al. NatHis-SMA study group. Natural history of Type 2 and 3 spinal muscular atrophy: 2-year NatHis-SMA study. Ann Clin Transl Neurol. 2021; 8(2): 359–373.
  19. Kolb SJ, Coffey CS, Yankey JW, et al. NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators. Natural history of infantile-onset spinal muscular atrophy. Ann Neurol. 2017; 82(6): 883–891.
  20. Balaji L, Farrar MA, D'Silva AM, et al. Decision-making and challenges within the evolving treatment algorithm in spinal muscular atrophy: a clinical perspective. Expert Rev Neurother. 2023; 23(7): 571–586.
  21. Pera MC, Coratti G, Forcina N, et al. Content validity and clinical meaningfulness of the HFMSE in spinal muscular atrophy. BMC Neurol. 2017; 17(1): 39.
  22. Hagenacker T, Wurster CD, Günther R, et al. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol. 2020; 19(4): 317–325.
  23. Finkel RS, Mercuri E, Darras BT, et al. ENDEAR Study Group. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017; 377(18): 1723–1732.
  24. Mercuri E, Darras BT, Chiriboga CA, et al. CHERISH Study Group. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med. 2018; 378(7): 625–635.
  25. Hodgkinson VL, Oskoui M, Lounsberry J, et al. A national spinal muscular atrophy registry for real-world evidence. Can J Neurol Sci. 2020; 47(6): 810–815.
  26. Łusakowska A, Wójcik A, Frączek A, et al. Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience. Orphanet J Rare Dis. 2023; 18(1): 230.
  27. Kotulska K, Chmielewski D, Mazurkiewicz-Bełdzińska M, et al. Safety, tolerability, and efficacy of a widely available nusinersen program for Polish children with Spinal Muscular Atrophy. Eur J Paediatr Neurol. 2022; 39: 103–109.
  28. Darras BT, Farrar MA, Mercuri E, et al. An integrated safety analysis of infants and children with symptomatic spinal muscular atrophy (SMA) treated with nusinersen in seven clinical trials. CNS Drugs. 2019; 33(9): 919–932.
  29. Haché M, Swoboda KJ, Sethna N, et al. Intrathecal injections in children with spinal muscular atrophy: nusinersen clinical trial experience. J Child Neurol. 2016; 31(7): 899–906.
  30. Aragon-Gawinska K, Seferian AM, Daron A, et al. Nusinersen in patients older than 7 months with spinal muscular atrophy type 1: A cohort study. Neurology. 2018; 91(14): e1312–e1318.
  31. Pane M, Coratti G, Sansone VA, et al. Italian Expanded Access Program Working Group. Nusinersen in type 1 spinal muscular atrophy: twelve-month real-world data. Ann Neurol. 2019; 86(3): 443–451.
  32. Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018; 14(10): 577–589.
  33. Darras BT, Crawford TO, Finkel RS, et al. Neurofilament as a potential biomarker for spinal muscular atrophy. Ann Clin Transl Neurol. 2019; 6(5): 932–944.
  34. Kolb SJ, Coffey CS, Yankey JW, et al. NeuroNEXT Clinical Trial Network and on behalf of the NN101 SMA Biomarker Investigators. Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study. Ann Clin Transl Neurol. 2016; 3(2): 132–145.
  35. Navarrete-Opazo A, Garrison S, Waite M. Molecular biomarkers for spinal muscular atrophy: a systematic review. Neurol Clin Pract. 2021; 11(4): e524–e536.