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Health and Economic Impact of Relapsing Forms of Multiple Sclerosis in Greece: The Storms Study

Yfantopoulos J1, Grigoriadis N2, Hatzikou M3*, Iliopoulos I4, Karageorgiou K5, Chantzaras A1, Kyritsis AP6, Papathanasopoulos P7, Rombopoulos G3, Tsimourtou V8, Vikelis M3, Treska X2, Tzortzis D5, Kostadima V6, Dimisianos N7 and Ralli S7

1School of Economics and Political Science, University of Athens, Greece

2Department of Neurology, Aristotle University of Thessaloniki, Greece

3Novartis Hellas S.A.C.I., Greece

4Department of Neurology, University of Thrace, Greece

5Department of Neurology, Iatriko Medical Centre of Athens, Greece

6Department of Neurology, University of Ioannina, Greece

7Department of Neurology, University of Patras, Greece

8Department of Neurology, University of Thessalia, Greece

*Corresponding Author:
Magdalini Hatzikou
Senior Health Economics Manager
Novartis Hellas. 12th Km National Road 1. Metamorfosis 14451, Greece
Tel: +30 6955460765
Fax: +30 2102897310
E-mail: [email protected]

Received date: September 08, 2015; Accepted date: October 21, 2015; Published date: October 28, 2015

Citation: Yfantopoulos J, Grigoriadis N, Hatzikou M, Iliopoulos I, Karageorgiou K, et al.(2015) Health and Economic Impact of Relapsing Forms of Multiple Sclerosis in Greece: The Storms Study. Pharmacoeconomics 1:102. doi: 10.4172/2472-1042.1000102

Copyright: © 2015 Yfantopoulos J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Background: Little information on costs and quality of life (QoL) of patients with Multiple Sclerosis (MS) has been published for Greece so far.

Objective: The objective of the study was to assess the socio-economic burden that MS imposes to Greek patients with relapsing forms of multiple sclerosis.

Methods: Information on demographics, disease history, resource consumption and productivity losses was collected from 200 patients recruited in six MS centres throughout Greece. Annual costs were estimated in 2011 unit costs. Health-related QoL (HRQoL) was measured with the EQ-5D questionnaire. Using the Expanded Disability Status Scale (EDSS), patients were stratified into those with mild (EDSS 0-3), moderate (EDSS 3.5-6.0) and severe (EDSS 6.5-7.5) disability. The perspective of the analysis was that of the national security fund (EOPYY).

Results: The mean annual cost per patient was estimated at €26,118. Higher disability increased costs substantially; €20,702 for mild, €32,126 for moderate and €45.442 for high severity patients. HRQoL was considerably impaired by disease progression. Patients with Secondary Progressive (SPMS) as expected had higher costs and lower HRQoL than Relapsing Remitting Multiple Sclerosis (RRMS) subjects, attributed to higher mean disability.

Conclusion: In accordance with other studies, MS imposes a considerable health and economic burden in Greece, which increases significantly with advancing disability.

Keywords

Multiple sclerosis; Economic impact; Health, Quality of life; EQ-5D; Greece

Introduction

Multiple sclerosis (MS) is the second most common nontraumatic cause of neurological disability in adults worldwide, with a considerable socioeconomic impact, which is disproportionate to the relatively limited prevalence of the disease [1]. In Greece, the estimated prevalence varies with location, ranging between 10.2/100,000 individuals in southern areas [2] and 119.61/100,000 people in western areas [3], with the most recent estimation being 23 cases per 100,000 individuals in northern areas [4]. Several epidemiological studies have demonstrated a gradual increase in prevalence and incidence of MS in Greece, placing most geographical areas in the medium and high-risk zone [3-7]. This gradual increase has been ascribed to the advances in diagnostic modalities and overall improved awareness [4].

The socio-economic burden of MS is particularly high both for patients, their families, as well as the national health system. The average annual cost per patient with MS is higher than for patients with many other, more common, chronic conditions [8,9]. The economic burden of MS is largely driven by the progression of disability and relapses, while MS-related symptoms of fatigue, depression, cognitive deterioration and behavioral disorders, pain, urinary and sexual dysfunction and comorbidities are also factors in the overall economic impact [10-15]. MS typically starts in early adulthood, so the disease has considerable economic consequences through lifelong decreased work capacity and productivity [16-20].

Furthermore, MS patients have lower health-related quality of life (HRQoL) than the general population, with the magnitude being similar to that of other chronic diseases [21,22]. Greater disability and relapses [16-20] ,other MS-related symptoms (fatigue, depression, cognitive deterioration and behavioral disorders, pain, urinary and sexual dysfunction), as well as treatment side effects and injection problems for some therapies, have been found to exert a detrimental influence on patients’ quality of life (QoL) [23,24]. Additionally, MS has an adverse impact on the social and family life of patients, as well as on the lives of their caregivers [25].

Although information about costs and QoL of MS patients is available for a number of European countries, no such data have been published for Greece so far. The objective of the study was to assess the health and economic burden that relapsing forms of MS impose to Greek MS patients and the Greek social security fund (EOPYY), respectively.

Materials and Methods

Study design and data collection

This was a multicentre, cross-sectional, retrospective, burden of disease study. The subjects were identified from six MS centres from various areas of the country. Adult patients suffering from either remitting-relapsing or secondary progressive MS with relapses were included in the study, provided they had given written informed consent. Patients that had limited capacity to participate in the study procedures, due to cognitive impairment or other factors, or were participating in another clinical study were excluded.

During a single visit, trained researchers completed a case report form by interviewing each patient on: i) demographics, ii) disease data (year of diagnosis, year of first symptoms, type of MS, Expanded Disability Status Scale [EDSS] score, number of relapses), iii) MS related comorbidities, iv) treatment-related information, v) resource utilization (inpatient and outpatient care, diagnostic and laboratory tests, medication, disability equipment, productivity loss and informal caregiving). Additionally, patients self-assessed their HRQoL with the EQ-5D questionnaire.

Costs calculation

This study adopts a bottom-up approach to estimate the mean annual costs per MS patient in Greece, from a social security fund perspective. Since MS is a chronic disease, a prevalence-based approach was selected, taking into account the use of resources during the previous year, using information which was gathered at a single point in time. A prevalence-based economic evaluation provides estimates of costs and health benefits of a certain population for a specific time horizon. Only MS specific resource utilization was collected. Costs were computed as the monetary value of resource utilization, i.e. the number of resource units consumed multiplied by the respective unit cost. Unit costs were obtained from publicly available sources in Greece (Table 1). MS related comorbidities’ economic burden was estimated as the total mean annual cost per patient related to each comorbidity, based on previous relevant literature [9,26]. Productivity loss of patients was approximated as the income reduction due to MS and the cost related to the early disability pension. The informal care cost was estimated by taking into account the total weekly hours spent for informal care (extrapolated to year), and using the mean gross income for Greece in 2011 (€19,018), divided by the number of hours worked, equally for working and non-working caregivers.

  Cost (€) Source
Disability pension (per month) 500 I.K.A. (https://www.ika.gr/gr/infopages/asf/pensions/handicap_sub/handicap_a.cfm)
Mean annual gross income per capita 19,018 Hellenic Statistical Authority
Inpatient and outpatient care  
Inpatient care (hospitalization; per day) 70.43 Joint Ministerial Decision Y4a/oik 1320/3-2-98 FEK B 99/10-2-1998
Out patient care (rehabilitation centre; 10 sessions) 150 Joint Ministerial Decision Y4a/oik 1320/3-2-98 FEK B 99/10-2-1998
Outpatient care (hospital; per visit) 54 Joint Ministerial Decision Y4a/oik 1320/3-2-98 FEK B 99/10-2-1998
Consultations (per visit)
General practitioner (EOPYY) 10 Law 4052/1-3-2012
Neurologist 75 Joint Ministerial Decision Y4a/G.P. oik 40620/6.12.2001 FEK Β 1643/10-12-2001
Other specialist 60 Joint Ministerial Decision Y4a/G.P. oik 40620/6.12.2001 FEK Β 1643/10-12-2001
Nurse 10 Law 4052/1-3-2012
Physiotherapist 15 Joint Ministerial Decision Y4a/G.P. oik 40620/6.12.2001 FEK Β 1643/10-12-2001
Psychologist 45 Joint Ministerial Decision Y4a/G.P. oik 40620/6.12.2001 FEK Β 1643/10-12-2001
Ergotherapist 15 Joint Ministerial Decision Y4a/G.P. oik 40620/6.12.2001 FEK Β 1643/10-12-2001
Optician 60 Joint Ministerial Decision Y4a/G.P. oik 40620/6.12.2001 FEK Β 1643/10-12-2001
Investigations (per exam)
Magnetic Resonance Imaging 237 Presidential Decree 163/88 FEK Α 75/22-4- 88
Computerized Tomography 71.11 Presidential Decree 163/88 FEK Α 75/22-4- 88
Lumbar Puncture 3.43 Presidential Decree 157/91 FEK A 62/30-4-91
Multiple Sclerosis related investments
Gait aids 206 I.K.A., DECISION 391/SYN. 39/13-12-01 Board IKA (IKA Ref. Circular 107/2001)
Manual wheelchair 890 I.K.A., DECISION 391/SYN. 39/13-12-01 Board IKA (IKA Ref. Circular 107/2001)
Electric wheelchair 5600 I.K.A., DECISION 391/SYN. 39/13-12-01 Board IKA (IKA Ref. Circular 107/2001)
Disease Modifying Treatments (yearly cost)
AVONEX 8449.61 Ministry of Health, Price List of Medicines for Human Use, May 2012 (D.T. 5/2012)
BETAFERON 7279 Ministry of Health, Price List of Medicines for Human Use, May 2012 (D.T. 5/2012)
COPAXONE 5823 Ministry of Health, Price List of Medicines for Human Use, May 2012 (D.T. 5/2012)
REBIF 44 8942 Ministry of Health, Price List of Medicines for Human Use, May 2012 (D.T. 5/2012)
REBIF 22 7513 Ministry of Health, Price List of Medicines for Human Use, May 2012 (D.T. 5/2012)
TYSABRI 17011.15 Ministry of Health, Price List of Medicines for Human Use, May 2012 (D.T. 5/2012)

Table 1: Unit costs (in euros) for hospitalization, patient follow-up, lab and imaging tests and health aid material.

Costs were grouped as: 1) direct medical costs (inpatient and outpatient care, consultations, investigations, treatments and MSrelated comorbidities), 2) direct non-medical costs (equipment investment, professional assistance, informal care) and 3) indirect costs (productivity loss, i.e., disability pension, percentage of income reduction).

QoL

The EQ-5D [27] is a widely used generic instrument for measuring HRQoL. It consists of a descriptive health state classification system with five dimensions, including: 1) mobility, 2) self-care, 3) usual activities, 4) pain/discomfort and 5) anxiety/depression, and a Visual Analogue Scale (VAS) assessing the overall perception of the subject’s health state. Each dimension of the descriptive system is measured with an ordinal three-point scale describing three levels of severity: i) no problems, ii) some problems, and iii) extreme problems. Together, these five dimensions with three levels for each dimension define a total of 243 health states, ranging from full to worst health. Health utilities were obtained based on time trade-off valuations from a general population study conducted at the United Kingdom, which have been found applicable in the Greek setting [28].

Analysis

Descriptive statistics (frequency, percentage, mean, standard deviation, median and interquartile range) were used for the analysis of the demographic and clinical characteristics of the sample, as well as the resource utilization and costs. To assess the effect of disability on costs and QoL of MS, along with demographic and clinical data, three categories were created based on EDSS score, as in previous studies [10-13,15], i.e., those with mild (EDSS 0-3), moderate (EDSS 3.5-6) and severe disability (EDSS 6.5-7.5). We conducted Jonckheere trend tests to examine whether a significant trend existed (ordered pattern of alternatives) in continuous data with advancing severity of the disease, as it was measured with the EDSS groups described; Cochran-Armitage tests were used for categorical responses. Similarly, the differences between MS type groups were compared with Mann-Whitney and x2 tests, for continuous and categorical data respectively. All comparisons were evaluated on the α=5% level. Confidence intervals (95%) of the costs were estimated by non-parametric bootstrapping. Statistical analysis was carried out with IBM SPSS Statistics 21 software package.

Results

Patient demographics and disease information

A total of 200 patients completed the study and were included in the analysis. Patients’ socio-demographics and disease information are presented in (Table 2). The sample had a mean age of 39.5 years, with 70.4% being females. The overall mean EDSS level was 3.1 (± 2.0), and the majority of subjects (62.5%) belonged to the mild disability subgroup (EDSS ≤ 3). Patients with less severe disease were younger (p<0.001); also the time period since first appearance of symptoms and diagnosis was shorter for less afflicted subjects (both p<0.001). A proportion of 86.5% was diagnosed as having RRMS, and 13.5% with SPMS. Finally, only 32% of the participants were employed or selfemployed at the time of the study.

  Overall
(n=200)
Severity   Type of MS  
EDSS 0-3
(n=125)
EDSS 3.5-6
(n=58)
EDSS 6.5-7.5
(n=17)
p-value* RRMS
(n=173)
SPMS
(n=27)
p-value†
Subjects (female: male ratio) 200 (70.0:30.0) 125 (26.4:73.6) 58 (36.2:63.8) 17 (35.3:64.7) 0.198 172 (72.7:27.3) 27 (55.6:44.4) 0.078
Age, years
Mean ± SD 39.5 ±10.3 35.9 ±8.7 44.4 ±9.9 49.8 ±9.1   37.9 ±9.5 50.3 ±8.6  
Median (IQR) 39.5 (14.7) 35 (13.5) 43.5 (12.0) 50 (12.0) <0.001 38.0 (13.0) 50.0 (12.0) <0.001
Cohabits with family/spouse, n (%) 177 (88.5%) 111 (89.5%) 53 (91.4%) 13 (76.5%)   154 (89.0%) 23 (85.2%) 0.503
Employment status, n (%)
Full time 53 (26.5%) 34 (27.2%) 17 (29.3%) 2 (11.8%) 0.868 49 (28.3%) 4 (14.8%) 0.347
Part time 11 (5.5%) 8 (6.4%) 2 (3.4%) 1 (5.9%)   11 (6.4%) 0 (0%)  
Employed 44 (22.0%) 25 (20.0%) 17 (29.3%) 2 (11.8%) 0.841 41 (23.7%) 3 (11.1%) 0.142
Self-employed 20 (10.0%) 17 (13.6%) 2 (3.4%) 1 (5.9%) 0.058 19 (11.0%) 1 (3.7%) 0.241
Housekeeping 29 (14.5%) 16 (12.8%) 9 (15.5%) 4 (23.5%) 0.256 24 (13.9%) 5 (18.5%) 0.524
Student 15 (7.5%) 14 (11.2%) 1 (1.7%) 0 (0%) 0.014 15 (8.7%) 0 (0%) 0.112
Unemployed 27 (13.5%) 21 (16.8%) 5 (8.6%) 1 (5.9%) 0.083 25 (14.5%) 2 (7.4%) 0.319
Type of MS, n (%) n.a.
RRMS 173 (86.5%) 124 (99.2%) 45 (77.6%) 4 (23.5%) <0.001 n.a. n.a.  
SPMS 27 (13.5%) 1 (0.8%) 13 (22.4%) 13 (76.5%)   n.a. n.a.  
Years since first diagnosis
Mean ± SD 9.2 ±5.9 7.4 ±5.2 11.7 ±6.1 14.2 ±5.2   8.5 ±5.7 14.1 ±5.2  
Median (IQR) 8.0 (7.0) 6.0 (7.0) 11.0 (9.0) 12.0 (5.0) <0.001 8.0 (7.0) 13.0 (7.0) <0.001
Years since first symptoms
Mean ±SD 11.9 ±6.7 9.9 ±6.1 15.1 ±6.7 16.2 ±5.5   11.1 ±6.5 17.2 ±5.6  
Median (IQR) 11.0 (10.0) 9.0 (8.5) 15.0 (11.3) 15.5 (9.0) <0.001 10.0 (9.0) 17.0 (10.3) <0.001
EDSS                
Mean ±SD 3.1 ±2.0 1.7 ±0.8 4.8 ±1.0 6.8 ±0.4   2.7 ±1.7 5.9 ±1.4  
Median (IQR) 2.5 (2.9) 2.0 (1.0) 4.5 (2.0) 6.5 (0.8) <0.001 2.0 (2.3) 6.0 (2.5) <0.001
Relapses in previous year
Mean ± SD 1.5 ±1.0 1.4 ±0.8 1.8 ±1.2 1.8 ±1.0   1.6 ±1.0 1.3 ±0.7  
Median (IQR) 1.0 (1.0) 1.0 (1.0) 1.5 (1.0) 1.5 (2.0) 0.070 1.0 (1.0) 1.0 (0) 0.223
Relapses requiring steroids in previous year
Mean ± SD 0.9 ±0.9 0.8 ±1.0 1.2 ±1.0 0.5 ±1.0   1.0 ±1.0 0.6 ±0.8  
Median (IQR) 1.0 (1.0) 1.0 (1.0) 1.0 (2.0) 0 (1.0) 0.351 1.0 (2.0) 0 (1.0) 0.128
MS related Comorbidities, n (%)
Depression/Anxiety 100 (50%) 59 (47.2%) 32 (55.2%) 9 (52.9%) 0.382 85 (49.1%) 15 (55.6%) 0.535
Urinary tracτ infection 69 (34.5%) 26 (20.8%) 34 (58.6%) 9 (52.9%) <0.001 57 (32.9%) 12 (44.4%) 0.243
Sleep disturbances 55 (27.5%) 30 (24.0%) 18 (31.0%) 7 (41.2%) 0.101 45 (26.0%) 10 (37.0%) 0.233
Mental problems 43 (21.5%) 25 (20.0%) 13 (22.4%) 5 (29.4%) 0.392 35 (20.2%) 8 (29.6%) 0.269
Osteoporosis 15 (7.5%) 3 (2.4%) 8 (13.8%) 4 (23.5%) <0.001 9 (5.2%) 6 (22.2%) 0.002
Hypertension 9 (4.5%) 5 (4.0%0 4 (6.9%) 0 (0%) 0.943 7 (4.0%) 2 (7.4%) 0.433
Arthritis 6 (3.0%) 2 (1.6%) 3 (5.2%) 1 (5.9%) 0.151 4 (2.3%) 2 (7.4%) 0.149

Table 2: Socio-demographics and disease information of the sample by EDSS level and MS type.

The most frequently reported comorbidities were depression (50%), urinary problems (34.5%), sleep disturbance (27.5%) and cognitive impairment (21.5%). Urinary tract infections and osteoporosis increased with the EDSS disability level (p<0.05). On average, RRMS patients were experiencing comorbidities to a lesser extent, though the difference was found statistically significant only for osteoporosis (p<0.05).

Resource utilisation

About 30% of the patients had required a hospital admission due to MS during the previous year (Table 3); a proportion of 46% had received outpatient care in a hospital and 4.5% in a rehabilitation centre, while 64.5% had consulted a specialist. The majority of patients had received a Disease Modifying Treatment (DMT; 84%), and 29% non-prescription medicines in the previous 3 months and 1 month of the study, respectively; a proportion of 76% had at least one Magnetic Resonance Imaging Scan and 5.5% a Lumbar Puncture performed, in the previous 3 months. Advancing disability appears to increase significantly the utilisation of outpatient care (both hospital and rehabilitation centre) and co-medication, though statistical significance is not established in all cases. RRMS patients utilise medical resources to a greater extent compared with SPMS subjects (with the exception of most prescribed drugs), though again the level of statistical significance is not reached in most items.

  Overall (n=200) Severity   Type of MS  
EDSS 0-3 (n=125) EDSS 3.5-6 (n=58) EDSS 6.5-7.5 (n=17) p-value* RRMS (n=173) SPMS (n=27) p-value†
Inpatient care (length of stay in days)
Hospital, n (%) 60 (30.0%) 36 (28.8%) 23 (39.7%) 1 (5.9%) 0.535 57 (32.9%) 3 (11.1%) 0.021
Mean ±SD 1.8 ±3.7 1.7 ±3.4 2.5 ±4.3 0.8 ±3.2   2.0 ±3.8 0.9 ±2.8  
Median (IQR) 0 (3.0) 0 (3.0) 0 (4.0) 0 (0) 0.945 0 (3.0) 0 (0) 0.033
Hospital due to relapses
Mean ±SD 2.2 ±3.4 2.0 ±3.3 2.9 ±3.5 1.3 ±4.1   2.3 ±3.4 1.5 ±3.4  
Median (IQR) 0 (4.0) 0 (3.0) 3.0 (5.0) 0 (0) 0.631 0 (4.0) 0 (2.0) 0.148
Outpatient care (visits)
Hospital, n % 92 (46.0%) 49 (39.2%) 32 (55.2%) 11 (64.7%) 0.010 77 (44.5%) 15 (55.6%) 0.284
Mean ± SD 3.8 ±6.8 3.6 ±7.5 4.2 ±5.9 4.0 ±4.5   3.9 ±7.1 3.3 ±4.2  
Median (IQR) 0 (4.0) 0 (4.0) 4.0 (4.0) 4.0 (4.0) 0.035 0 (4.0) 4.0 (4.0) 0.615
Rehabilitation centre, n % 9 (4.5%) 1 (0.8%) 5 (8.6%) 3 (17.6%) <0.001 7 (4.0%) 2 (7.4%) 0.433
Mean ± SD 1.2 ±9.1 0 ±0.4 3.7 ±16.7 0.7 ±1.6   1.3 ±9.8 0.3 ±1.1  
Median (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.001 0 (0) 0 (0) 0.452
Consultations (public & private), n % 129 (64.5%) 79(63.2%) 41 (70.7%) 9 (52.9%) 0.938 115 (66.5%) 14 (51.9%) 0.140
Physiotherapist,
Mean visits ± SD 12.4 ±38.0 3.9 ±19.4 24.6 ±48.6 33.2 ±71.2   11.9 ±37.5 15.4 ±41.6  
Median visits (IQR) 0 (0) 0 (0) 0 (34.0) 0 (16.0) 0.001 0 (0) 0 (0) 0.530
Ergotherapist
Mean visits ± SD 0.7 ±10.2 0 ±0 2.5 ±18.9 0 ±0   0.8 ±10.9 0 ±0  
Median visits (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.274 0 (0) 0 (0) 0.639
Neurologist
Mean visits ± SD 3.7 ±5.7 3.9 ±6.2 3.5 ±4.9 2.4 ±4.0   3.8 ±5.9 2.8 ±4.0  
Median visits (IQR) 0 (4.0) 0 (6.0) 0 (5.0) 0 (6.0) 0.388 0 (6.0) 0 (4.0) 0.620
Psychologist
Mean visits ± SD 0.7 ±4.2 0.2 ±1.6 1.7 ±7.3 0.7 ±2.1   0.7 ±4.4 0.7 ±2.7  
Median visits (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.019 0 (0) 0 (0) 0.343
Other specialist
Mean visits ± SD 2.0 ±4.9 1.9 ±5.4 2.5 ±4.2 1.4 ±2.8   2.1 ±5.2 1.5 ±3.0  
Median visits (IQR) 0 (4.0) 0 (0) 0 (4) 0 (2.0) 0.150 0 (4.0) 0 (0) 0.598
General practitioner
Mean visits ±SD 0.2 ±1.3 0.2 ±1.3 0.2 ±1.6 0 ±0   0.2 ±1.4 0 ±0  
Median visits (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.557 0 (0) 0 (0) 0.426
Nurse (hospital)                
Mean visits ± SD 0.1 ±1.4 0.2 ±1.8 0 ±0 0 ±0   0.1 ±1.5 0 ±0  
Median visits (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.447 0 (0) 0 (0) 0.693
Optician
Mean visits ± SD 0.1 ±0.7 0.1 ±0.5 0.2 ±1.2 0 ±0   0.1 ±0.8 0 ±0  
Median visits (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.729 0 (0) 0 (0) 0.426
Investigations (tests)
Magnetic Resonance Imaging, n (%) 152 (76.0%) 95 (76.0%) 47 (81.0%) 10 (59.8%) 0.455 138 (79.8%) 14 (51.9%) 0.002
Mean number ± SD 1.1 ±0.9 4.8 ±3.6 4.4 ±3.2 2.8 ±2.4   1.2 ±0.9 0.5 ±0.5  
Median number (IQR) 1.0 (1.0) 4.0 (4.0) 4.0 (0) 4.0 (4.0) 0.176 1.0 (1.0) 1.0 (1.0) <0.001
Computerized Tomography, n (%) 1 (0.5%) 1 (0.8%) 0 (0%) 0 (0%) 0.476 1 (0.6%) 0 (0%) 0.692
Mean number ±SD 0.1 ±0.1 0 ±1.6 0 ±0 0 ±0   0 ±0.1 0 ±0  
Median number (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.447 0 (0) 0 (0) 0.693
Lumbar Puncture, n (%) 11 (5.5%) 9 (7.2%) 2 (3.4%) 0 (0%) 0.143 10 (5.8%) 1 (3.7%) 0.660
Mean number± SD 0.1 ±0.2 0.4 ±1.2 0 ±0.8 0 ±0   0.1 ±0.2 0 ±0.2  
Median number (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.150 0 (0) 0 (0) 0.681
MS Treatment, n (%)
On DMT 168 (84%) 103 (82.4%) 50 (86.2%) 15 (88.2%) 0.417 145 (83.8%) 23 (85.2%) 0.857
Not currently treated, but have received DMT in the past 46 (23%) 27 (36.5%) 16 (64.0%) 3 (60.0%) 0.023 42 (24.3%) 4 (14.8%) 0.476
Prescribed drugs, n (%)                
Antidepressants 48 (24.0%) 19 (15.2%) 22 (37.9%) 7 (41.2%) <0.001 37 (21.4%) 11 (40.7%) 0.029
Immunosuppressant’s 3 (1.5%) 0 (0%) 1 (1.7%) 2 (11.8%) 0.001 0 (0%) 3 (11.1%) <0.001
Anti-spasticity drugs 40 (20.0%) 9 (7.2%) 24 (41.4%) 7 (41.2%) <0.001 29.1 (16.8%) 11 (40.7%) 0.004
Urological drugs 29 (14.5%) 12 (9.6%) 14 (24.1%) 3 (17.6%) 0.039 25.1 (14.5%) 4 (14.8%) 0.960
Analgesic drugs 46 (23.0%) 25 (20%) 16 (27.6%) 5 (29.4%) 0.209 38.9 (22.5%) 7 (25.9%) 0.698
Steroids 24 (12.0%) 11 (8.8%) 12 (20.7%) 1 (5.9%) 0.319 22 (12.7%) 2 (7.4%) 0.430
Sleep disturbances treatment 17 (8.5%) 5 (4.0%) 9 (15.5%) 3 (17.6%) 0.005 11.9 (6.9%) 5 (18.5%) 0.045
Fatigue drugs 19 (9.5%) 6 (4.8%) 10 (17.2%) 3 (17.6%) 0.007 13 (7.5%) 6 (22.2%) 0.015
Cognitive dysfunction drugs 2 (1.0%) 1 (0.8%) 1 (1.7%) 0 (0%) 0.929 1 (0.6%) 1 (3.7%) 0.129
OTC drugs, n % 58 (29.0%) 38 (30.4%) 15 (25.9%) 5 (29.4%) 0.686 54 (31.2%) 4 (14.8%) 0.081

Table 3: Annual direct medical resource utilisation of the sample by EDSS level and MS type¥.

Modification of living space or vehicle or use of walking aids due to MS was necessary for 14% of the subjects (Table 4). The frequency of patients reporting any MS-related investment (p<0.001) and use of professional or informal care due to MS (both p<0.001) increased significantly with worsening severity of the disease; notably, utilization of informal care was much more frequently reported (39%) than professional care (6.5%). RRMS patients were receiving less informal and professional assistance (both p<0.001), and had less overall MS related modifications and equipment investments than the SPMS subjects (p<0.001). Apparently, due to higher disability level and lower relapse rate, SPMS patients require more informal care support rather than health care services utilisation.

  Overall (n=200) Severity   Type of MS  
EDSS 0-3 (n=125) EDSS 3.5-6 (n=58) EDSS 6.5-7.5 (n=17) p-value* RRMS (n=173) SPMS (n=27) p-value†
MS related investments previous 12 months, n (%) 28 (14.0%) 4 (3.2%) 15 (25.9%) 9 (52.9%) <0.001 18 (10.4%) 10 (37.0%) <0.001
House modifications, n (%) 10 (5.0%) 2 (1.6%) 3 (5.2%) 5 (29.4%) <0.001 6 (3.5%) 4 (14.8%) 0.012
Car modifications, n (%) 6 (3.0%) 1 (0.8%) 3 (5.2%) 2 (11.8%) 0.007 4 (2.3%) 2 (7.4%) 0.149
Gait aids, n (%) 20 (10.0%)   11 (19.0%) 7 (41.2%) <0.001 13 (7.5%) 7 (25.9%) 0.003
Manual wheelchair, n (%) 3 (1.5%) 0 (0%) 2 (3.4%) 1 (5.9%) 0.018 1 (0.6%) 2 (7.4%) 0.007
Electric wheelchair , n (%) 2 (1.0%) 0 (0%) 1 (1.7%) 1 (5.9%) 0.022 1 (0.6%) 1 (3.7%) 0.129
Professional assistance, n (%) 13 (6.5%) 4 (3.2%) 3 (5.2%) 6 (35.3%) <0.001 7 (4.0%) 6 (22.2%) <0.001
Nurse at home
Mean hours per week ± SD 2.0 ±0 2.0 ±0 0 ±0 0 ±0   2.0 ±0 0 ±0  
Median hours per week (IQR) 2.0 (0) 2.0 (0) 0 (0) 0 (0) 1.000 2.0 (0) 0 (0) 1.000
Home helper
Mean hours per week ± SD 16.5 ±24.8 5.5 ±4.1 4.7 ±4.6 29.8 ±32.6   5.1 ±4.0 29.8 ±32.6  
Median hours per week (IQR) 8.0 (23.0) 5.0 (8.0) 2.0 (0) 25.0 (46.0) 0.158 2.0 (8.0) 25.0 (46.0) 0.138
Personal assistant
Mean hours per week ± SD 34.7 ±22.5 0 ±0 0 ±0 34.7 ±22.5   0 ±0 34.7 ±22.5  
Median hours per week (IQR) 40.0 (0) 0 (0) 0 (0) 40.0 (0) 1.000 0 (0) 40.0 (0) 1.000
Informal care, n (%) 78 (39.0%) 28 (22.4%) 36 (62.1%) 14 (82.4%) <0.001 57 (32.9%) 6 (77.8%) <0.001
Mean hours per week ± SD 7.08 ±16.2 2.1 ±5.8 11.7 ±20.3 28.2 ±27.7   4.7 ±12.5 22.4 ±26.1  
Median hours per week (IQR) 0 ±7.0 0 (0) 5.5 (13) 24.0 (38.0) <0.001 0 (4.0) 13.0 (30.0) <0.001

Table 4: Indirect resource utilisation data of the sample by EDSS level and MS type¥.

About one third of the patients (31%) had been retired due to MS, and 33.5% reported receiving MS-related disability benefits during the time of the study (Table 5); both percentages were higher for patients experiencing SPMS (p<0.005). 14% of the subjects reported that they had taken a sick leave due to MS during the previous 3 months of the study; patients in a more severe condition recorded more sick days on average, though not statistically significant. A proportion of 9% of the sample reported a permanent reduction in work hours, and 5% listed a work change and/or income reduction due to the disease.

  Overall (n=200) Severity   Type of MS  
EDSS 0-3 (n=125) EDSS 3.5-6 (n=58) EDSS 6.5-7.5 (n=17) p-value* RRMS (n=173) SPMS (n=27) p-value†
Retired due to age, n (%) 3 (1.5%) 0 (0%) 3 (5.2%) 0 (0%) 0.145 2 (1.2%) 1 (3.7%) 0.311
Retired due to MS, n (%) 62 (31.0%) 32 (25.6%) 21 (36.2%) 9 (52.9%) 0.013 47 (27.2%) 15 (55.6%) 0.003
On disability payment, n (%) 67 (33.5%) 34 (27.2%) 23 (39.7%) 10 (58.8%) 0.005 51 (29.5%) 16 (59.3%) 0.002
Sick leave due to MS past 3 months, n (%) 28 (14%) 18 (14.4%) 8 (13.8%) 2 (11.8%) 0.782 26 (15%) 2 (7.4%) 0.288
Mean days ±SD 2.6 ±11.7 1.9 ±9.0 2.9 ±12.6 6.5 ±22.1   2.9 ±12.5 0.5 ±2.0  
Median days (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.939 0 (0) 0 (0) 0.278
Reduction in work hours, n (%) 18 (9.0%) 13 (10.4%) 4 (6.9%) 1 (5.9%) 0.384 16 (9.2%) 2 (7.4%) 0.758
Work change and income reduction, n (%) 10 (5.0%) 7 (5.6%) 2 (3.4%) 1 (5.9%) 0.763 10 (5.8%) 0 (0%) 0.200
Percentage of income reduction
Mean ±SD 2.2 ±11.1 2.5 ±12.3 1.7 ±9.2 1.8 ±7.3   2.5 ±11.9 0 ±0  
Median (IQR) 0 (0) 0 (0) 0 (0) 0 (0) 0.850 0 (0) 0 (0) 0.229

Table 5: Productivity loss of the sample by EDSS level and MS type.

Costs

The mean cost per patient per year was estimated at €26,118, with MS treatments being the largest contributor to the overall cost (48.4%) and for all disability and MS type subgroups (Tables 6 and 7). Total cost increased significantly (p<<0.001) across the EDSS disability level groups; €20,702 for mild disability (EDSS 0-3), €32,126 for moderate disability (EDSS 3.5-6) and €45.442 for high disability patients (EDSS 6.5-7.5). Total direct medical and non-medical, and indirect costs all increased significantly with advancing disability (all p<0.05). The component costs of outpatient care, MS treatments, MS-related comorbidities, MA-related investments, professional and informal assistance and economic burden due to early retirement (disability pension) all enlarged significantly (all p<0.05) with increasing disability. Notably, the share of informal care in the total cost rose from 5.7% in patients with mild condition to 32.6% in subjects with severe disability (14.6% overall contribution).

  Overall
(n=200)
Severity  
EDSS 0-3
(n=125)
EDSS 3.5-6
(n=58)
EDSS 6.5-7.5
(n=17)
p-value*
Mean±SD 95% CI Median (IQR) Mean±SD 95% CI Median (IQR) Mean±SD 95% CI Median (IQR) Mean±SD 95% CI Median (IQR)
Inpatient care 129 ±261 98-164 0 (211) 117 ±241 78-159 0 (211) 175 ±305 105-261 0 (282) 54 ±222 54-215 0 (0) 0.937
Outpatient care 294 ±626 218-380 216 (216) 206 ±404 143-280 0 (216) 495 ±969 302-732 216 (486) 254 ±244 165-368 216 (432) 0.002
Consultations 630 ±868 512-754 300 (900) 483 ±642 379-594 300 (720) 902 ±1127 663-1176 480 (1260) 791 ±1091 346-1302 240 (1440) 0.099
Investigations 261 ±211 231-291 237 (237) 274 ±224 237-314 237 (237) 266 ±194 221-315 237 (62) 153 ±144 98-209 237 (237) 0.138
MS treatments 12643 ±4982 11947-13401 17011 (8562) 11701 ±5223 10844-12671 8942 (8562) 14023 ±4177 12879-15062 17011 (8069) 14859 ±4010 13056-16439 17011 (4281) 0.001
MS releted Comorbidities 5644 ±6290 4778-6534 3377 (10210) 4606 ±5494 3717-5567 3377 (5946) 7091 ±7323 5379-8995 5156 (10989) 8349 ±6587 4960-11512 10216 (12681) 0.002
OTC 17 ±76 9-28 0 (10) 14 ±50 7-21 0 (12) 22 ±118 4-53 0 (6) 26 ±51 0-51 0 (35) 0.806
Direct medical costs 19618 ±8161 18525-20818 19459 (10207) 17399 ±7322 16087-18702 17961 (9474) 22973 ±8474 20898-25006 21457 (13361) 24486 ±7243 20480-27883 24847 (12565) <0.001
MS related Investments 68 ±648 2-135 0 (0) 0 ±0 0-0 0 (0) 119 ±852 4-350 0 (0) 394 ±1572 12-1157 0 (0) 0.002
Professional assistance 188 ±1214 64-363 0 (0) 28 ±173 4-60 0 (0) 28 ±155 4-79 0 (0) 1904 ±3818 498-3856 0 (2860) 0.001
Informal care 3816 ±8393 2830-4885 0 (4123) 1171 ±3106 725-1707 0 (515) 6299 ±10500 3988-8885 2834 (7343) 14793 ±14263 8611-20908 12883 (19582) <0.001
Direct non-medical costs 4072 ±8677 2947-5300 0 (4638) 1199 ±3101 750-1740 0 (515) 6446 ±10522 4063-9065 3607 (7730) 17091 ±14228 10530-23462 16315 (19011) <0.001
Income reduction 418 ±2109 166-708 0 (0) 472 ±2341 155-844 0 (0) 328 ±1750 164-820 0 (0) 336 ±1384 336-1007 0 (0) 0.850
Retirement due to MS * 2010 ±2839 1590-430 0 (6000) 1632 ±2681 1200-2064 0 (6000) 2379 ±2961 1759-3000 0 (6000) 3529 ±3044 2471-4588 6000 (6000) 0.008
Indirect costs 2428 ±3324 1988-2908 0 (6000) 2104 ±3388 1538-2656 0 (6000) 2707 ±3200 1880-3509 0 (6000) 3865 ±2943 2453-5277 6000 (6000) 0.020
Total costs 26118 ±14922 24297-28084 22090 (17302) 20702 ±9813 19003-22466 20625 (12309) 32126 ±16110 28376-35711 27231 (20017) 45442 ±18486 36929-54179 42809 (21954) <0.001

Table 6: Costs per patient per year by EDSS level (in € 2011), 95% CI.

  RRMS
(n=173)
SPMS
(n=27)
p-value†
Mean±SD 95% CI Median (IQR) Mean ±SD 95% CI Median (IQR)
Inpatient care 139 ±268 99-185 0 (211) 60 ±196 10-115 0 (0) 0.033
Outpatient care 308 ±667 226-412 216 (216) 200 ±231 112-291 216 (216) 0.791
Consultations 641 ±883 516-763 300 (900) 564 ±778 302-871 300 (960) 0.458
Investigations 283 ±214 254-313 237 (237) 123 ±121 79-167 237 (237) <0.001
MS treatments 12418 ±5062 11584-13210 17011 (8562) 14082 ±4241 12165-15736 17011 (8069) 0.168
MS releted comorbidities 5202 ±5802 4421-6129 3377 (7173) 8480 ±8396 5676-11452 5946 (12780) 0.061
OTC 18 ±81 9-31 0 (13) 9 ±30 1-20 0 (0) 0.131
Direct medical costs 19009 ±7839 17829-20192 19267 (10181) 23518 ±9214 20057-27080 23674 (13870) 0.025
MS related Investments 39 ±494 0-114 0 (0) 256 ±1247 8-729 0 (0) 0.002
Professional assistance 30 ±172 8-60 0 (0) 1199 ±3139 324-2343 0 (0) <0.001
Informal care 2562 ±6523 1629-3621 0 (2061) 11852 ±13419 7710-16953 7214 (15975) <0.001
Direct non-medical costs 2630 ±6559 1675-3710 0 (2061) 13307 ±13755 9163-18223 7730 (15460) <0.001
Income reduction 484 ±2262 176-896 0 (0) 0 ±0 0-0 0 (0) 0.227
Retirement due to MS 1769 ±2744 1353-2150 0 (6000) 3556 ±3004 2222-4667 6000 (6000) 0.002
Indirect costs 2252 ±3345 1756-2782 0 (6000) 3556±3004 2222-4667 6000 (6000) 0.020
Total costs 23892 ±12570 21809-25851 21655 (15070) 40381±20365 33806-47552 39321 (32361) <0.001

Table 7: Costs per patient per year by MS type (in € 2011), 95% CI.

RRMS subjects were on average less disabled than SPMS patients (EDSS mean score 2.7 vs. 5.9 respectively; Table 2), which is reflected in the lower costs observed in the RRMS subgroup; the mean cost per patient per year was €23,892 for RRMS and €40,381 for SPMS subjects respectively. Direct medical and non-medical as well as indirect costs all were significantly different between groups (all p<0.05); component costs of inpatient care and investigations were statistically significantly larger in RRMS patients (p<0.05), whereas economic burden due to MS-related investments, informal care and early retirement (disability pension) was greater in participants with SPMS (all p<0.05).

QoL

Anxiety/depression problems were reported by 74% of the patient population, while 67.5% had at least some mobility issues, 59% were experiencing usual activities limitations, 45% were complaining of pain/ discomfort and 27% had at least some self-care difficulties (Table 8). The frequency of patients reporting problems with mobility, self-care and usual activities was increasing significantly with worsening disability (all p<0.001), and it was found higher in patients with SPMS (all p<0.001).

  Overall
(n=200)
Severity   Type of MS  
EDSS 0-3
(n=125)
EDSS 3.5-6
(n=58)
EDSS 6.5-7.5
(n=17)
p-value* RRMS
(n=173)
SPMS
(n=27)
p-value†
EQ-5D dimensions, subjects reporting problems (%)
Mobility * † 135 (67.5%) 61 (48.8%) 57 (98.3%) 17 (100%) <0.001 108 (62.4%) 27 (100%) <0.001
Self-care * † 54 (27.0%) 9 (7.2%) 29 (50.0%) 16 (94.1%) <0.001 33 (19.1%) 21 (77.8%) <0.001
Usual activities* † 118 (59.0%) 50 (40.0%) 51 (87.9%) 17 (100%) <0.001 93 (53.8%) 25 (92.6%) <0.001
Pain/ discomfort 90 (45.0%) 54 (43.2%) 28 (48.3%) 8 (47.1%) 0.567 76 (43.9%) 14 (51.9%) 0.442
Anxiety/ depression 148 (74.0%) 86 (68.8%) 50 (86.2%) 12 (70.6%) 0.140 128 (74.0%) 20 (74.1%) 0.992
EQ-5D utility index * †
Mean ±SD 0.601 ±0.287 0.683 ±0.255 0.508 ±0.266 0.316 ±0.309   0.639 ±0.263 0.359 ±0.318  
Median (IQR) 0.689 (0.296) 0.735 (0.228) 0.620 (0.525) 0.260 (0.583) <0.001 0.725 (0.298) 0.516 (0.553) <0.001
VAS * †
Mean ±SD 67.9 ±21.0 75.2 ±18.5   53.2 ±10.0   70.5 ±19.7 51.6 ±22.3  
Median (IQR) 70 (30) 80.0 (21.0) 60.0 (31.0) 60.0 (35.0) <0.001 75.0 (25.0) 50.0 (40.0) <0.001

Table 8: HRQoL results by EDSS level and MS type.

The mean utility score of the sample was 0.601 (± 0.287); HRQoL index decreased significantly with worsening disability (p<0.001), i.e., 0.683 (± 0.255) in mild, 0.508 (± 0.266) in moderate, and 0.316 (± 0.309) in high disability patients. SPMS group’s HRQoL was more impaired than that of the RRMS (p<0.001); the mean EQ- 5D index was 0.359 (± 0.318) and 0.639 (± 0.263) for SPMS and RRMS subjects respectively. VAS results concerning self-assessed health were in congruence with these findings; the mean VAS score of the whole sample was 67.9 (± 21.0), and a decreasing trend was again established with increasing severity (p<0.001). Finally, the SPMS group was associated with a significantly lower mean VAS score compared with the RRMS group (51.6 vs. 70.5, respectively; p<0.001).

Discussion

The objective of this study was to estimate the health and economic burden of MS in Greece, while offering valuable insights into the way disease severity and MS type affect the related costs.

The mean annual cost per patient was estimated at €26,118. This is comparable to the results of a recent study across 5 European countries, in which the mean annual cost per patient ranged between €20,738 and €29,400 [10-15]. Worsening disability was associated with a substantially increased economic impact of the disease, which is in accordance with the findings of most published studies [10-13,15,19,29-36]. According to the existing literature [10-20], severe disability, when compared to mild, is associated with increased costs for hospitalizations, consultations, laboratory tests and other drugs, although the cost of immunomodulatory drugs is reduced. In our research, total direct medical and non-medical as well as indirect costs indeed increased considerably with advancing disability, with statistical significances established for the majority of their components. Furthermore, treatment cost retained its prominence in all disability and MS type subgroups, though its share in the total cost gradually decreased, which may be attributed to the patient recruitment, as it is discussed subsequently. Informal care contributed significantly to the total cost (14.6%); its contribution increased from 5.7% in patients with mild to 32.6% in subjects with severe disability, confirming the importance of informal care for MS patients, which is strongly associated with the severity of the disease [10-15,18,19,29-36]. Higher mean disability in patients with SPMS compared with RRMS subjects resulted in almost doubled total costs, in congruence with what is observed in other European countries [10,12-15]; total direct medical and non-medical as well as indirect costs all were significantly different between the 2 groups.

HRQoL was found considerably impaired by MS. Psychological and mobility problems and difficulties related to usual activities were reported by the majority of the patients. The mean utility score in the sample was 0.601 (VAS mean score 67.9), which is lower than the corresponding value in the general population, though somewhat higher than in other similar reports [16-20,37], which could be attributed to the lower mean EDSS level of this study. Finally, higher severity and SPMS type of MS decreased HRQoL, which is consistent with the international literature [10-15,18,19,29-36].

There are several limitations related to the recruitment of patients from hospital MS centres, as it might result in a sample of subjects with higher mean disability [38]. Nevertheless, in our study, the number of patients which were assigned to the high disability group (EDSS 6.5- 7.5) was relatively low (n=17). In fact, patients with EDSS >7.5 were not represented in our study, hence costs might has been actually underestimated due to the lack of high resource consuming patients. Currently, there are no country-scale studies of MS in Greece with epidemiological data concerning different patient disability categories, which could have been used as a demographic guide in the study design. Additionally, we approximated the productivity loss due to MS by the patient-reported reduction in their income, which may not be an appropriate proxy for estimating productivity losses, if there is a benefit to mitigate the fall in income.

Furthermore, the questionnaire explicitly requested resource utilization due to MS, but it still might have captured consumption unrelated to MS, thus yielding inflated costs. This possible limitation is particularly relevant to the comorbidities’ economic burden, which was estimated as the total mean annual cost per patient, and not only as co-medication costs. Nevertheless, MS is a well-defined condition, and unrelated comorbidity is relatively low due to the young age of the patients [19,38]. A degree of recall bias introduced by participants regarding their reports about past events or experiences may also be present, as it is a common peril among studies with a retrospective design [41]. Finally, the sample size of patients without a recent relapse was not large enough to estimate the specific cost related to relapses, which would have been a valuable piece of information.

In conclusion, the STORMS study contributes to the scarce information on costs and health of MS patients in Greece. In view of the increasing economic and HRQoL burden with worsening disability, the use of MS treatments that can effectively delay the progression of the disease may reduce the detrimental impact of the disease on patient and caregiver lives, as well as on society as a whole.

Funding

This study was funded by Novartis (Hellas) S.A.C.I.

Disclosures and Conflict of Interest

J Yfantopoulos has received honoraria and research grants from Novartis. N Grigoriadis has received honoraria and research grants from Novartis, Teva, Biogen Idec, Bayer, Merck-Serono and Sanofi-Genzyme. K Karageorgiou is a member of advisory boards of Genzyme, Teva, Genesis Pharma and Novartis. P Papathanasopoulos has participated as a member of Advisory Boards and got unrestricted research grants from Novartis, Genesis, TEVA, Serono and Bayer. D Tzortzis has received research grants from Novartis. V Tsimourtou and S Ralli has received research grants from Novartis, Bayer and Genesis and Novartis. N Dimisianos has received honoraria from Novartis, Genesis Pharma and Merck, travel expenses from Teva, Merck, Novartis and an unresticted research grant from Genesis Pharma. I Iliopoulos, V Kostadima, AP Kyritsis, X Treska and A. Chantzaras have nothing to disclose. M.Chatzikou and G. Rombopoulos are employees of Novartis Hellas and M. Vikelis was working in Novartis Hellas during the analysis of the study.

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