Impact on healthcare resource utilization of multiple sclerosis in Spain

Multiple sclerosis (MS) is a chronic, autoimmune disease characterised by inflammation of the central nervous system that leads to demyelination, axonal loss and progressive neuronal degeneration [1]. A prevalence of 125 cases/100,000 inhabitants was found in Spain affecting mainly young adults [2‐5].

Multiple sclerosis progresses from episodic attacks followed by periods of remission (relapsing-remitting MS [RRMS]) to a more progressive state (secondary progressive MS [SPMS]) in approximately 80% of patients [1]. Primary progressive MS (PPMS) accounts for 10% of the overall population with MS and differs from RRMS and SPMS patients, in that progression consists of gradual worsening of neurologic disability from symptom onset [1]. Disease progression is linked to the accumulation of disability, which overall, is faster for patients with PPMS than for patients with RRMS [1]. Current MS disease-modifying therapies (DMTs) are used with the aim of reducing the number of relapses, their severity, and slowing the disability’s progression [6].

The age of onset of MS is generally in the most financially productive time of the patients’ lives and consequently has a substantial economic burden on patients, their families, and society as a whole [7‐10]. The European total annual cost of MS was €14.6 billion in 2010 (1.8% of the total annual economic cost of all brain disorders) [11]. A recent study involving 16,808 patients with MS in 16 European countries found that work capacity of MS patients declined from 82 to 8% with advancing disease, and utility declined from normal population values to less than zero [12]. Patients with PPMS present higher healthcare utilization than patients with SPMS and RRMS, due to different provider visits, emergency visits, and hospital admissions [13]. Disease-modifying therapies are the main cost drivers for patients with mild disease severity, while for those with more advanced disability these are production losses and informal care [10, 12].

Mental and neurological disorders also have a substantial economic impact in Spain (equivalent to almost 8% of the country’s GDP) with a mean yearly per-patient cost of €30,050 for MS patients [14, 15]. However, information about the use of healthcare resources and associated costs among patients with MS in Spain is limited. The objective of this study was to assess the healthcare resources utilization of MS patients in Spain according to the degree of disability in order to provide detailed and updated information about the economic burden of the disease.

A total of 222 patients were included (Figure 1). The mean (SD) age was 45.5 (12.5) years and 64.4% were female. Prevalence of MS was 71 cases/100,000 inhabitants. Relapsing-remitting MS was the most common clinical form (62.2% of the patients). The median EDSS score was 2.5 (range: 1.0–8.5). The impact of comorbidity was significantly greater in the severe disability group vs. the no to moderate disability group: mean number of comorbidities (6.0 vs. 4.5; p = 0.001), Charlson Index (1.0 vs. 0.7; p = 0.005), and RUBs (3.2 vs. 2.9; p = 0.003). Demographic and clinical characteristics of the patients are shown in Table 2. Intramuscular interferon beta-1a (30.6%), subcutaneous interferon beta-1a (23.9%) and glatiramer acetate (18%) were the most common disease-modifying treatments administered.

Multiple sclerosis is a chronic disabling disease that is associated with reduced quality of life and a high socioeconomic impact [7]. Physical disability at diagnosis is the main determinant of the economic burden, with 13% increased annual costs for each additional point from baseline EDSS [24]. In addition, the costs increase with more severe disability, especially when patients lose their upper limb function and independence (EDDS score > 7.0) [25].

The therapeutic landscape of treatment has changed dramatically over the last years. An increasing number of new drugs have recently shown encouraging results for the management of RRMS due to their proven higher efficacies compared to first-generation DMTs [6]. However, despite the availability of more treatment options, costs for all DMTs have increased substantially [10]. In addition, the early disease onset of MS has a significant impact on the patient’s most productive working years, leading to huge potential societal costs associated with this productivity loss [10]. Patients are less likely to be employed, are more likely to require time off work and to retire early compared to people without MS [7, 9, 12].

The impact on the costs of managing patients with MS is increasingly an area of interest [26‐29]. However, comparing costs between countries with different socioeconomic, cultural, epidemiological background, and different systems for organizing and funding healthcare is very difficult [12, 30].

This study shows an overall annual mean cost per MS patient of €25,103. This mean cost was significantly higher in patients with severe disability compared than those with no-moderate disability (€29,242 and €23,157, respectively; p = 0.013). Total cost was associated to the number of relapses, time since diagnosis, and age (p = 0.001, 0.023, and 0.037, respectively). Indirect costs and MS therapy accounted for 61% and 31.7% of the total costs, respectively.

In Spain, the available data for cost of MS is limited [12, 31‐34]. These findings concur with prior studies. In a cost-of-illness analysis based on information from 1848 patients, Kobelt et al. found that the total mean costs per patient were driven by the distribution of the disease severity levels [30]. Workforce participation decreased from approximately 70% in the early disease stages to less than 5% in the very late stages. Productivity losses increased more than eightfold in patients with an EDSS score of 0–1 vs. 8–9. In another study with a sample of 200 MS patients in Barcelona, Casado et al. found that the main drivers for direct costs were DMTs in low disability stages and caregiver costs in severe disability stages [32]. Overall, direct healthcare costs accounted for 60% of total cost; within these direct costs DMTs accounted for 78% in the early disability stages to 11% in the later disability stages. The correlation of disability with the increasing economic burden of MS was also shown in the TRIBUNE study [34]. The mean cost per patient per year was €20,659 for patients with mild disease severity, while patients with moderate MS incurred more than double that cost (€43,948). DMTs were the most expensive cost component for patients with mild and moderate disability (58% and 32%, respectively) [34].

Missing values and differences on diagnostic codification are usual limitations related to studies with population databases [35]. McDonald 2010 criteria were not used in the study because our healthcare database collected diagnosis following only IPC-2 and ICD-9 classifications. In addition, concomitant medications were not evaluated. This study did not include any non-healthcare direct costs, classified as “out-of-pocket” costs paid by the patient/family, as they were not recorded in the database. The only direct costs considered were those relating to the public health system and the area of influence of the patient. Another limitation was the absence of informal caregivers to calculate informal costs. Sick leave (temporary or permanent) may in turn be a limited indicator of indirect costs as premature death and informal costs were not considered. In addition, standard cost for sick leave should have been applied, rather than the specific costs depending on patients’ income. Despite these limitations, these results reflect the economic impact of MS and how these vary between different disability levels.

Patients with MS show high healthcare resource utilization and large work productivity losses that cumulatively impose a substantial economic burden on the healthcare system and society as a whole. This burden was enhanced upon disease progression.

Therefore, a more proactive management strategy, including earlier use of high-efficacy DMTs and close monitoring of the clinical and radiological response to treatment, is recommended to slow or halt the progression of physical and cognitive impairments in patients with MS [36, 37]. No evidence of disease activity is emerging as a new standard MS outcome and may be associated with improved long-term disability.

Additional research focusing on direct healthcare and indirect costs as well as standardised methodologies to calculate costs are necessary to determine the association between the disease evolution and economic burden.