Spinal muscular atrophy: epidemiology and health burden in children — a Polish national healthcare database perspective before introduction of SMA-specific treatment
, 2, 3, 4, 5, 6, 1, 7, 8
Abstract
Introduction: Spinal muscular atrophy (SMA) is one of the most frequent autosomal recessive neuromuscular disorders. It leads to progressive muscle weakness, premature death or permanent ventilation. Significant disability, scoliosis, severe pulmonary infections and other problems require in- and outpatient medical care. Various approaches have been used to evaluate SMA epidemiology, healthcare burden and adherence to standard of care. The recent introduction of pharmacological treatment in a large SMA population will change the course of the disease and the healthcare requirements of patients.
Material and methods: We have used the National Health Fund database to identify children with SMA and the healthcare service they received in the pre-pharmacological treatment era. Pivotal phase II and III medical trials for nusinersen were conducted between 2013 and 2015. The National Treatment Programme of SMA patients with nusinersen in our country was started in January 2019. The year 2014 was used to evaluate incident cases.
Results: 51 new SMA cases (incidence 1:7,356) and 518 SMA patients younger than 18 were identified in 2014. 32 (6.2%) deaths were recorded, half in the first two years of life. 35 (6.8%) patients received palliative and 115 (22.2%) long-term care (including assisted ventilation). A total number of 3,057 days of hospital stay were reported. Only 65/518 (12.6%) patients did not receive publicly-funded healthcare service other than specialist or general practitioner’s consultation.
Conclusions: SMA caused significant mortality and morbidity in children. The National Health Fund database can be used to reliably record incident cases and track the care provided to paediatric SMA patients.
Keywords: spinal muscular atrophyepidemiologyhealthcare burdenincidence
References
- Lefebvre S, Bürglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995; 80(1): 155–165.
- Zerres K, Davies KE. 59th ENMC International Workshop: Spinal Muscular Atrophies: recent progress and revised diagnostic criteria 17-19 April 1998, Soestduinen, the Netherlands. Neuromuscul Disord. 1999; 9(4): 272–278.
- Zerres K, Rudnik-Schöneborn S, Forrest E, et al. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci. 1997; 146(1): 67–72.
- Jedrzejowska M, Wiszniewski W, Zimowski J, et al. Application of a rapid non-invasive technique in the molecular diagnosis of spinal muscular atrophy (SMA). Neurol Neurochir Pol. 2005; 39(2): 89–94.
- Wirth B, Herz M, Wetter A, et al. Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Hum Genet. 1999; 64(5): 1340–1356.
- Verhaart IEC, Robertson A, Leary R, et al. A multi-source approach to determine SMA incidence and research ready population. J Neurol. 2017; 264(7): 1465–1473.
- Bladen CL, Thompson R, Jackson JM, et al. Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. J Neurol. 2014; 261(1): 152–163.
- Wang CH, Finkel RS, Bertini ES, et al. Participants of the International Conference on SMA Standard of Care. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007; 22(8): 1027–1049.
- Finkel RS, Mercuri E, Meyer OH, et al. SMA Care group. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018; 28(3): 197–207.
- Mercuri E, Finkel RS, Muntoni F, et al. SMA Care Group. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018; 28(2): 103–115.
- Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016; 388(10063): 3017–3026.
- 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.
- 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.
- Jędrzejowska M, Kostera-Pruszczyk A. Spinal muscular atrophy — new therapies, new challenges. Neurol Neurochir Pol. 2020; 54(1): 8–13.
- Andersen JB, Engeland A, Owe JF, et al. Myasthenia gravis requiring pyridostigmine treatment in a national population cohort. Eur J Neurol. 2010; 17(12): 1445–1450.
- Jedrzejowska M, Milewski M, Zimowski J, et al. Incidence of spinal muscular atrophy in Poland — more frequent than predicted? Neuroepidemiology. 2010; 34(3): 152–157.
- 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.
- Jędrzejowska M, Gos M, Zimowski JG, et al. Novel point mutations in survival motor neuron 1 gene expand the spectrum of phenotypes observed in spinal muscular atrophy patients. Neuromuscul Disord. 2014; 24(7): 617–623.
- Norwood FLM, Harling C, Chinnery PF, et al. Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population. Brain. 2009; 132(Pt 11): 3175–3186.
- Farrar MA, Vucic S, Johnston HM, et al. Pathophysiological insights derived by natural history and motor function of spinal muscular atrophy. J Pediatr. 2013; 162(1): 155–159.
- Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014; 83(9): 810–817.
- Cobben JM, Lemmink HH, Snoeck I, et al. Survival in SMA type I: a prospective analysis of 34 consecutive cases. Neuromuscul Disord. 2008; 18(7): 541–544.
- Chung BHY, Wong VCN, Ip P. Spinal muscular atrophy: survival pattern and functional status. Pediatrics. 2004; 114(5): e548–e553.
- Bach JR, Saltstein K, Sinquee D, et al. Long-term survival in Werdnig-Hoffmann disease. Am J Phys Med Rehabil. 2007; 86(5): 339–348.
- Finkel RS, Sejersen T, Mercuri E, et al. ENMC SMA Workshop Study Group. 218th ENMC International Workshop: revisiting the consensus on standards of care in SMA Naarden, The Netherlands, 19-21 February 2016. Neuromuscul Disord. 2017; 27(6): 596–605.
- Bach JR, Gonçalves MR, Hon A, et al. Changing trends in the management of end-stage neuromuscular respiratory muscle failure: recommendations of an international consensus. Am J Phys Med Rehabil. 2013; 92(3): 267–277.
- Barsdorf AI, Sproule DM, Kaufmann P. Scoliosis surgery in children with neuromuscular disease: findings from the US National Inpatient Sample, 1997 to 2003. Arch Neurol. 2010; 67(2): 231–235.
- Więckowska B. Healthcare Needs Maps — Evidence Informed Healthcare Policy. Journal of Health Policy and Outcomes Research. 2017; 1(1): 14–20.
