Counting the cost of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a predominantly childhood neuromuscular disease, representing one of the most common genetic causes of infant mortality. The degeneration of lower motor neurons that occurs in SMA leads to a progressive decline in muscle strength^1–3. However, the profile of disease progression varies substantially between patients, resulting in the identification of as many as five distinct clinical sub-groups (referred to as Type 0–IV)⁴. Type I SMA, otherwise known as Werdnig-Hoffman disease, is the most common form of the disease, with onset occurring by 6 months of age. Difficulties with feeding and breathing contribute to premature death, normally occurring within the first 2 years of life in the absence of palliative care⁵.

Exciting developments in the field of molecular genetic research over the last couple of decades have firmly established the cause of SMA for the vast majority of patients: low expression levels of survival motor neuron (SMN) protein resulting from mutations in the survival motor neuron (SMN1) gene^1,2. The subsequent generation of genetically-accurate animal models of SMA has led to the identification of key events occurring during disease pathogenesis^2,3,6,7. In turn, this has resulted in the development of potential disease-modifying therapies for SMA. Several different strategies have successfully demonstrated that restoring levels of SMN protein during critical developmental time-windows (through the use of gene therapy, antisense oligonucleotide treatment or small molecule approaches) leads to a robust amelioration of disease symptoms and significant extension of life span in animal models^5,8,9. A second generation of SMN-independent therapies are also currently progressing through pre-clinical development, targeting a range of other molecular pathways with the potential to further modify disease. These include therapies targeting muscle strength¹⁰, Rho-kinase (ROCK) pathways¹¹, and ubiquitination pathways^12,13. Taken together, these developments have raised considerable excitement amongst the SMA patient and research communities, encouraging the belief that disease-modifying therapies are near.

The strong pre-clinical data from animal models has resulted in several human patient clinical trials for SMA being established over the last few years. Although none have yet proceeded through all stages of the full clinical trial process required in order to receive full regulatory approval, initial signs have been encouraging, especially for trials using gene therapy or antisense oligonucleotide treatment to increase SMN levels¹⁴. Although clinical data are not yet available, it appears likely that at least one of these approaches will result in the first disease-modifying therapy for SMA. The extent to which these treatment strategies modulate a patient’s disease phenotype remains to be clarified, although they are unlikely to represent a full “cure”⁸. Nevertheless, the encouraging findings from ongoing clinical trials raise the likelihood that a disease-modifying therapy will be made available to clinicians caring for SMA patients in the medium- to long-term. This raises a large number of potential financial, logistical, and ethical issues that have not previously been considered relevant to SMA.

Previous, largely qualitative, studies have highlighted the high levels of burden that are experienced by individuals with SMA and their families, impacting across all aspects of daily life¹⁵. The emotional and social costs of SMA are, therefore, relatively well documented and not to be under-estimated. However, until recently, very few studies have attempted to establish the economic/financial costs of SMA. One area where these costs have previously been studied is with regards to the cost-effectiveness of universal prenatal screening for SMA (one suggested intervention to reduce disease incidence). For example, a recent study by Little et al.¹⁶ suggested a cost of around $5.0 million per case averted. However, more broad-reaching studies examining the total costs of care for SMA patients are likely to be more relevant to the pharmaceutical industry and for future policy and funding decisions made by healthcare regulators that will determine access to, and provision of, new disease-modifying therapies for SMA.

In the current issue of Journal of Medical Economics, Armstrong et al.¹⁷ report on an important study of the economic/financial costs of SMA, based on Department of Defense Military Healthcare System (MHS) data spanning from 2003–2012¹⁷. By comparing healthcare costs of more than 200 SMA patients with those of more than 700 individuals belonging to a comparator cohort (selected using a 3:1 match based on age and gender), they revealed a significant increase in total expenditure for SMA patients. For example, the median total expenditure for SMA patients over an average of ∼7 years was $83,652, almost $80,000 higher than the total expenditure recorded for the comparator group. As expected, further stratification of these data to examine costs specifically in SMA patients with more severe forms of the disease (likely to represent Type I SMA patients, although information on the precise clinical diagnosis wasn’t available to the researchers) identified even higher costs (median cost of $167,921). Although this study has several limitations (acknowledged by the authors), including a lack of detailed patient information to facilitate accurate grouping of patients by disease sub-type and absence of information concerning additional financial costs beyond those recorded in the MHS records, resulting in a likely under-estimate of the full economic/financial costs encountered, the authors have provided invaluable insights into the real-world costs of healthcare for SMA.

The costs identified in the Armstrong et al.¹⁷ study are specifically related to those incurred by accessing healthcare provision available in the US. It is, therefore, of interest to make comparisons with a near-contemporaneous study from Klug et al.¹⁸ reporting on the economic burden of SMA in Germany. This study examined a similar number of SMA patients (just under 200 in total), covering SMA Types I–III in patients from birth through to 73 years of age. They estimated that the average annual “cost of illness” (COI) for each patient in 2013 was €70,566. As in the Armstrong et al.¹⁷ study, the highest costs were incurred in patients with SMA Type I (increasing to €107,807 per year). Interestingly, informal care costs and indirect costs incurred by patients and their caregivers (factors that were likely to be under-estimated in the Armstrong et al.¹⁷ study) contributed significantly to the overall COI in Germany. Taken together, these two recent studies reveal that the high economic/financial costs of SMA are not associated with just one specific healthcare system, being replicated across multiple countries. It is of note, therefore, that the estimated total economic burden of SMA in Germany is ∼€106.5 million per year¹⁸. The total economic burden in larger countries, such as the US, is, therefore, likely to be proportionately higher.

Although the burden of SMA cannot, and should never be, reduced to an analysis of economic/financial cost, the insights provided by studies such as those from Armstrong et al.¹⁷ will contribute significantly to our understanding of the full societal impact of diseases such as SMA, helping to inform and guide therapy development and provision over the coming years.

Transparency

Declaration of funding

The author's laboratory has received funding from the UK SMA Research Consortium (SMA Trust) and Muscular Dystrophy UK.

Declaration of financial/other relationships

THG is Chair of the Scientific Advisory Board of the SMA Trust and is named on a patent application submitted by the University of Edinburgh for the use of beta-catenin inhibitors for the treatment of SMA. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.