Analyse médico-économique du dépistage néonatal de l’amyotrophie spinale en Fédération Wallonie-Bruxelles

L’objet de cette thèse doctorale en sciences de la santé publique est d’étudier la mise en place du dépistage néonatal de l’amyotrophie spinale (SMA), d’évaluer les implications économiques de la SMA et d’estimer l’impact médico-économique de ce dépistage néonatal en Belgique. Les développements cliniques actuels dans le domaine de la SMA convergent pour démontrer l'importance d'un traitement précoce, avec une efficacité encore accrue lorsque le traitement est pré-symptomatique. L'identification des patients pré-symptomatiques nécessite un dépistage néonatal à grande échelle, que nous avons mis en place dans le cadre d’un projet pilote sur la Fédération Wallonie-Bruxelles à partir de mars 2018. Les études de coûts et qualité de vie ont révélées un impact considérable de la SMA sur le quotidien des patients et de leur famille, mais aussi sur la société qui supporte les coûts des soins de santé. L’analyse médico-économique a comparé le dépistage néonatal de la SMA suivi d'un traitement modificateur de la maladie avec d’autre part le comparateur : les soins habituels pour les patients ayant reçu un diagnostic post-symptomatique. Le dépistage néonatal est associé à un gain de qualité de vie (QALY) conséquent, pour un coût par QALY gagné favorable, conduisant à la dominance de la stratégie. En conclusion, cette thèse de doctorat a permis d’expliquer le développement et le suivi du dépistage néonatal de la SMA en Fédération Wallonie-Bruxelles, de relever les implications considérables de la SMA en termes de coût et de qualité de vie, et de suggérer l’intérêt économique du dépistage néonatal par rapport au traitement tardif. Compte tenu de l’évolution motrice des patients traités avant l'apparition des symptômes ainsi que l’amélioration spectaculaire de leur qualité de vie liée à la santé, le dépistage néonatal offre la possibilité d’améliorer la qualité de vie et l’espérance de vie des patients atteint de SMA pour un coût supplémentaire raisonnable par rapport à l’absence de dépistage lorsque des traitements sont disponibles

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported

Dépistage et traitement de l’amyotrophie spinale

editorial reviewe

Newborn screening of neuromuscular diseases.

peer reviewedNeuromuscular diseases represent an heterogenous group of more than 400 diseases, with a very broad phenotypic spectrum. Given their rarity and complexity, neuromuscular diseases are often diagnosed with a very significant delay after which irreversible muscle damage may limit the efficacy of treatments when available. In this context, neonatal screening could constitute a solution for early detection and treatment. A systematic review of the literature in PubMed up to May 1, 2021, was conducted according to PRISMA guidelines, including classical neuromuscular diseases and diseases with a clear peripheral nervous system involvement (including central nervous system disease with severe neuropathy). We found seven diseases for which newborn screening data were reported: spinal muscular atrophy (9), Duchenne muscular dystrophy (9), Pompe disease (8), X-linked adrenoleukodystrophy (5), Krabbe disease (4), myotonic dystrophy type 1 (1), metachromatic leukodystrophy (1). The future of newborn screening for neuromuscular disorders pass through a global technological switch, from a biochemical to a genetic-based approach. The rapid development of therapy also requires the possibility to quickly adapt the list of treated conditions, to allow innovative therapies to achieve their best efficacy

SMA: REGISTRIES, BIOMARKERS & OUTCOME MEASURES: P.187 Systematic literature review of the economic burden and economic evaluations in spinal muscular atrophy

New treatments in spinal muscular atrophy (SMA) have led to a complete change in the pattern in the use of health care resources in this disease. Through all over the world, the very high cost of innovative medication has led to public debates largely expressed in mainstream medias. We have systematically reviewed studies evaluating the cost of SMA and economic evaluations of spinal muscular atrophy. The review was conducted according to PRISMA guidelines and included original articles published between January 1, 1998 and March 2020. Seven studies reporting the cost of SMA were identified. The average annual costs of untreated SMA1 (including early onset and SMA before one year), were relatively similar across the different studies, ranging from $106,000 to$140,000 per year. On the other hand, the costs for SMA 2, 3 and 4 were mainly presented together (ranging from $23,000 to$115,000), despite a high heterogenicity in clinical conditions leading to very different health care resource consumption. Five economic evaluations were published between 2017 and 2020 and included innovative disease modifying medications. Three assessed the cost-effectiveness of nusinersen against standards of care, one of them two treatments (nusinersen and zolgensma) against standards of care and one compared Nusinersen and Zolgensma. All studies used a decision-analytic model to assess the cost- effectiveness and are based on same clinical trials involving a limited number of patients. Due to the extremely high cost of treatment, the incremental cost-effectiveness ratio of drugs versus no treatment is generally above $200,000, leading to no cost-effective results. In conclusion, all studies converge to demonstrate the significant economic cost of SMA, especially SMA1, but a better evaluation of the cost related to other forms is needed. A few economic evaluations suggest that drugs delivered in post-symptomatic phase at current prices are actually not cost-effective at commonly accepted cost-effectiveness threshold. No economic evaluation of newborn screening has yet been conducted

SMA: REGISTRIES, BIOMARKERS & OUTCOME MEASURES: P.191 Preliminary data for the cost-effectiveness assessment of the newborn screening for SMA in Belgium

Neonatal screening is becoming increasingly important in the spinal muscular atrophy (SMA) landscape. Yet there is a growing set of evidences that early pre-symptomatic management is much more efficient than post- symptomatic treatment, there is however no information available on the cost-effectiveness of SMA newborn screening (NBS). Such health economic analysis is nevertheless very important to convince policy makers to allocate funds for NBS. We will present the health-economic data of pre-symptomatic and post-symptomatic treated patients in Belgium that will further be used to assess the cost-effectiveness of NBS. Between March 2018 and February 2020, screening was conducted among 71,000 newborns, among which 9 were detected with SMA. All but one identified patients were treated before the onset of symptoms: 5 with nusinersen (one was mildly symptomatic at the time of treatment), 2 with Zolgensma, 1 with Risdiplam and the last one to be determined. Survival, costs and quality of life of these 9 patients (aged between 10 days and 18 months) are currently prospectively collected. In addition, data from 3 additional asymptomatic patients who were siblings of affected children are also collected. Survival, health care resources consumption and quality of life data have also been collected on symptomatic treated and untreated patients. For untreated patients, we collected prospectively the data during two years in 81 patients (53 patients with SMA Type 2, 9 non-ambulant with SMA Type 3 and 19 ambulant with SMA Type 3). We are also collecting similar data prospectively in 30 symptomatic patients treated with nusinersen and 2 untreated patients, aged between 4 months and 60 years (9 patients with SMA 1, 14 patients with SMA 2, and 9 patients with SMA 3). Two-thirds of these patients already have at least 2 years of follow-up. Using these three sets of data, we are currently developing a model to assess the cost-effectiveness of newborn screening for SMA. We will present the preliminary results issued from this model

Newborn screening programs for spinal muscular atrophy worldwide: where we stand and where to go

peer reviewedSpinal muscular atrophy (SMA) is a rare and devastating disease. New disease- modifying treatments have recently been approved and early treatment has been related to a better outcome. In this context, several newborn screening (NBS) programs have been implemented. The aim of the study was to obtain a global overview on the current situation and perspectives on SMA NBS. We conducted a survey and contacted experts from 152 countries, from which we gathered 87 responses. We identified 9 SMA NBS programs that have so far detected 288 newborns with SMA out of 3,674,277 newborns screened. Funding, screening methods, organisation, and consent process were variable between SMA NBS programs. Many respondents pointed the lack of cost/benefit data as a major obstacle to SMA NBS implementation. In the next four years, our data suggest a 24 % coverage of newborns from countries where a disease-modifying drug is available and 8,5 % coverage in countries with no diseases-modifying drugs. The annual proportion of newborns to be screened in the coming years is expected to increase steadily. The experts expressed a strong need for the implementation of SMA NBS as means to improve care for patients with SMA

Correspondence on: “Discrepancy in Spinal Muscular Atrophy Incidence findings in newborn screening programs: the influence of carrier screening?” by Kay et al

peer reviewe

Infantile spinal muscular atrophy: Therapeutic (R)evolution

Summary: Spinal muscular atrophy (SMA) is an auto-somal recessive neuromuscular disorder. The infantile form is the most common genetic cause of infantile death due to respiratory insufficiency. The disorder is caused by the premature death of motor neurons of anterior horn, leading to progressive weakness and muscular atrophy. Longtime considered as untreatable, the pathology knew a real revolution during the last two years. Views on this terrible disease have completely changed, changing, therefore, the management of the patients and constituting new challenges. © 2019 Revue Medicale de Liege. All Rights Reserved