Newborn screening for SMA improves patients’ outcome, cost-effective

Newborn screening for spinal muscular atrophy (SMA) is less costly and leads to improved quality of life (QoL) for patients and healthcare costs savings for countries when compared to treating symptomatic patients. This is because newborn screening enables early detection and treatment of patients with SMA before symptoms occur, said Dr Matthias Bischof, senior director, Global Health Economics, Novartis Gene Therapies, Zürich, Switzerland.

SMA is a neurodegenerative disorder as a result of a mutation in the survival motor neuron 1 (SMN1) gene which reduces the expression of SMN protein leading to muscle weakness and often early death, if untreated, usually before the second birthday. [Genet Med 2011;13(7):686–694] The usual standard of care was to support patients with multidisciplinary care. However, the improved understanding of the pathogenetic mechanisms of SMA led to the development of three therapeutic approaches namely, nusinersen, onasemnogene abeparvovec-xioi and risdiplam. These new therapies are available in many countries and have led to improved survival in patients with SMA. [Nat Rev Dis Primers 2022;8(1):52]

Although effective treatment is available for patients with SMA, the greatest benefit is derived from these therapies when they are applied prior to disease onset as shown in the SPR1NT study. [Nat Med 2022;28(7):1381–1389] Hence, the urgent need for newborn screening to detect SMA in presymptomatic patients. SMA can be characterized by the number of SMN2 genes.

In the SPR1NT study, patients with either two or three of these genes were enrolled and treated with onasemnogene abeparvovec-xioi. Patients with two copies were more likely to develop severe symptoms while those with three copies were more likely to develop less severe symptoms. In the 18-month post treatment follow up, 79 percent of the presymptomatic patients with two copies of SMN2 achieved independent standing and 64 percent achieved independent walking in comparison with patients who received post symptomatic therapy (5 percent, respectively). Of the patients with three copies of SMN2, 93 percent achieved independent walking in the first 24 months. The study is relatively small hence the reason for not achieving 100 percent—one child reached the motor milestone of walking outside of the 24-month follow-up period.

The Bayley-III scale was used to describe the development of fine-motor and gross-motor function over time in the patients in the SPR1NT study. All the children (with three copies of SMN2) who received gene therapy followed the natural trajectory of healthy children. The study concluded the greatest benefit from these treatments are seen when they are initiated prior to disease onset ie, identifying patients during newborn screening. There is a huge potential for improvement in survival and reaching the motor milestones ie, the ability to sit, stand and walk.

Since autopsy studies have shown SMA starts in utero with rapid degeneration, it is a race against time to detect patients before they developed symptoms. [Brain 2002;125:1624–1634] The decline of motor neurons over time for different types of patients including, SMA type 1 patients who present with symptoms earlier on and the ones who are most affected, is very rapid immediately from birth. Hence, these patients need immediate attention shortly after birth and this is only possible with newborn screening. [Mol Neurobiol 2018;55(8):6307–6318] The loss of motor neurons is irreversible, and the process continues leading to rapid deterioration. Thus, study authors recommended gene therapy is initiated as soon as possible after birth. [Nat Med 2022;28(7):1381–1389]

Cost-effectiveness of newborn screening for SMA
Bischof noted that the WHO criteria for newborn screening is relevant in Malaysia whereby there should be an important health problem for which therapy is available along with a suitable screening test accepted by the population, and the cost of case-finding should be economically balanced in relation to possible expenditure on medical care as a whole. [WHO. Wilson JMG, Jungner G. Principles and practice of screening for disease. Available at https://apps.who.int/iris/bitstream/handle/10665/37650/WHO_PHP_34.pdf?sequence=17&isAllowed=y. Accessed on 1 February 2023.]

In economic evaluations of newborn screening for SMA, the points of consideration include patients with genetic diagnosis, the majority of them without symptoms, improvement in patients’ QoL, survival benefits, and reduction in healthcare costs. In addition, caregivers’ QoL, drug and administration costs, caregiver costs, and productivity were also studied. The original model for economic evaluations of newborn screening for SMA was developed by the University of Groningen in The Netherlands. Each model compared a scenario with newborn screening vs a scenario without newborn screening and the main health outcome was quality-adjusted life years (QALYs).

Cost-effectiveness studies conducted in The Netherlands, Europe, US, and Australia showed that newborn screening for SMA is effective in reducing healthcare costs for presymptomatic patients compared with those who were clinically diagnosed. [Value Health 2022;25(10):1696–1704, Dev Med Child Neurol 2023;65(1):67–77, J Pediatr 2020;227:274–280.e2, Int J Neonatal Screen 2022;8(3):45] The study in The Netherlands showed newborn screening followed by treatment increased QALYs by about 320 among presymptomatic patients with total healthcare cost reduction of more than €12 million. [Value Health 2022;25(10):1696–1704] In the US, newborn screening followed by treatment resulted in an incremental cost-effectiveness ratio (ICER) of more than US$330,000 per event-free life year saved vs no screening and no treatment. [J Pediatr 2020;227:274–280.e2]