Miguel A. Macı´as-Islas • Isaac F. Soria-Cedillo • Merced Velazquez-Quintana • Victor M. Rivera • Vero´nica I. Baca-Muro • Edith A. Lemus-Carmona • Erwin Chiquete Limited data exist on the costs of care of patients with multiple sclerosis (MS) in low- to middleincome nations. The purpose of this study was to describe the economic burden associated with care of Mexican patients with relapsing-remitting MS in a representative sample of the largest institution of the Mexican public healthcare system. We analysed individual data of 492 patients (67 % women) with relapsing-remitting MS registered from January 2009 to February 2011 at the Mexican Social Security Institute. Direct costs were measured about the use of diagnostic tests, disease-modifying therapies (DMTs), symptoms control, medical consultations, relapses, intensive care and rehabilitation. Four groups were defined according to DMT alternatives: (1) interferon beta (IFNb)-1a, 6 million units (MU); (2) IFNb-1a, 12MU; (3) IFNb-1b, 8MU; and (4) glatiramer acetate. All patients received DMTs for at least 1 year. The most frequently used DMT was glatiramer acetate (45.5 %), followed by IFNb-1a 12MU (22.6 %), IFNb-1b 8MU (20.7 %), and IFNb-1a 6MU (11.2 %). The mean cost of a specialised medical consultation was €74.90 (US $107.00). A single relapse had a mean total cost of €2,505.97 (US $3,579.96). No differences were found in annualised relapse rates and costs of relapses according to DMT. However, a significant difference was observed in total annual costs according to treatment groups (glatiramer acetate being the most expensive), mainly due to differences in unitary costs of alternatives. From the public institutional perspective, when equipotent DMTs are used in patients with comparable characteristics, the costs of DMTs largely determine the total expenses associated with care of patients with relapsing-remitting MS in a middle-income country.

1. Acta Neurol Belg
DOI 10.1007/s13760-013-0200-z
ORIGINAL ARTICLE
Cost of care according to disease-modifying therapy in Mexicans
with relapsing-remitting multiple sclerosis
´
Miguel A. Macıas-Islas • Isaac F. Soria-Cedillo • Merced Velazquez-Quintana
´
Victor M. Rivera • Veronica I. Baca-Muro • Edith A. Lemus-Carmona •
Erwin Chiquete
•
Received: 22 January 2013 / Accepted: 16 April 2013
Ó Belgian Neurological Society 2013
Abstract Limited data exist on the costs of care of
patients with multiple sclerosis (MS) in low- to middleincome nations. The purpose of this study was to describe
the economic burden associated with care of Mexican
patients with relapsing-remitting MS in a representative
sample of the largest institution of the Mexican public
healthcare system. We analysed individual data of 492
patients (67 % women) with relapsing-remitting MS registered from January 2009 to February 2011 at the Mexican
Social Security Institute. Direct costs were measured about
the use of diagnostic tests, disease-modifying therapies
(DMTs), symptoms control, medical consultations,
´
M. A. Macıas-Islas (&)
´
´
Jefe del Departamento de Neurologıa, UMAE, Centro Medico
´
Nacional de Occidente, IMSS, Belisario Domınguez #1000, Col.
Independencia Oriente, C.P. 44340 Guadalajara, Jal, Mexico
e-mail: miguelangelmacias@hotmail.com
´
M. A. Macıas-Islas
Department of Neurosciences, Centro Universitario de Ciencias
de la Salud, Universidad de Guadalajara, Guadalajara, Jal,
Mexico
I. F. Soria-Cedillo Á V. I. Baca-Muro Á E. A. Lemus-Carmona
Department of Health Economics, Novartis Mexico, Mexico
City, DF, Mexico
M. Velazquez-Quintana
Department Health Research, Hospital Regional #1, IMSS,
Chihuahua, Chi, Mexico
V. M. Rivera
The Maxine Mesinger MS Comprehensive Care Centre, Baylor
College of Medicine, Houston, TX, USA
E. Chiquete
Department of Neurology and Psychiatry, Instituto Nacional de
´
´
´
Ciencias Medicas y Nutricion ‘‘Salvador Zubiran’’, Mexico City,
DF, Mexico
relapses, intensive care and rehabilitation. Four groups
were defined according to DMT alternatives: (1) interferon
beta (IFNb)-1a, 6 million units (MU); (2) IFNb-1a, 12MU;
(3) IFNb-1b, 8MU; and (4) glatiramer acetate. All patients
received DMTs for at least 1 year. The most frequently
used DMT was glatiramer acetate (45.5 %), followed by
IFNb-1a 12MU (22.6 %), IFNb-1b 8MU (20.7 %), and
IFNb-1a 6MU (11.2 %). The mean cost of a specialised
medical consultation was €74.90 (US $107.00). A single
relapse had a mean total cost of €2,505.97 (US $3,579.96).
No differences were found in annualised relapse rates and
costs of relapses according to DMT. However, a significant
difference was observed in total annual costs according to
treatment groups (glatiramer acetate being the most
expensive), mainly due to differences in unitary costs of
alternatives. From the public institutional perspective,
when equipotent DMTs are used in patients with comparable characteristics, the costs of DMTs largely determine
the total expenses associated with care of patients with
relapsing-remitting MS in a middle-income country.
Keywords Costs of care Á Glatiramer acetate Á
Healthcare Á Interferon Á Multiple sclerosis
Introduction
Multiple sclerosis (MS) is a disabling neurodegenerative
disease caused by immune-mediated destruction of myelinated central nerve fibres [1]. Most individuals experience
their first symptoms between the ages 20 and 40 years [2]
and as a consequence, it leads to high costs associated with
lost of productivity, employment and quality of life [3–5].
On one hand, the introduction of new costly diseasemodifying therapies (DMTs) may contribute to the
123

2. Acta Neurol Belg
elevated healthcare costs; but on the other hand, these
highly effective interventions may diminish long-term
healthcare system expenses through a reduction of disabilities, hospitalisations associated with relapses and loss
of productive years. Careful evaluations of the cost-benefit
ratio become essential for the formulation of efficient
health policies, especially in countries where the healthcare
system depends primarily on public resources [6–8]. Thus,
the cost analysis of a disabling disease such as MS is an
important topic around the world. Unfortunately, for most
developing countries MS represents an under diagnosed
disease, and therefore, information on the epidemiology as
well as the economic burden of this disabling disorder is
scarce [9–12]. Countries going through the economic-epidemiological transition are facing new healthcare challenges unrecognised in the previous decades. The aim of
this study was to determine the economic burden associated with care of Mexican patients with relapsing-remitting
MS, in a representative sample of the largest institution of
the Mexican healthcare system.
revised 2005 McDonald criteria, and treated at least for
12 months with one of the first-line DMTs (IFNb-1a 6 MU,
IFNb-1a 12 MU, IFNb-1b 8 MU or glatiramer acetate).
The costs of institutional resources were determined
according to the Unitary Costs per Level of Medical
Attention (the lower the level, the higher the Institutional
costs, with lower patient’s economic participation) and
Diagnosis-Related Groups (DRG). The cost of each relapse
was established according to DRGs, which consider the
mean cost of institutional resources use per patient. Costs
are expressed in US Dollars (US $) and Euro (€) at a
currency exchange rate of (Mexican pesos) MXN $13.28
per US $1.00, and €0.70 per US $1.00. To estimate the
institutional burden of disease in a standardised fashion,
direct costs on individual patient data were used to construct an economic simulation (using TreeAge Pro 2010,
TreeAge Software Inc, Williamstown, MA, USA) of the
patterns of resource usage in a standardised time frame of
12 months. Patients with similar disease states were
grouped for a comparable analysis of resources usage. For
each health state (group of patients) the following formula
was employed:
Methods
In this retrolective observational study, we directly analysed individual clinical records of patients with relapsingremitting MS pertaining to the Mexican Social Security
Institute (Instituto Mexicano del Seguro Social, IMSS), the
largest institution of the Mexican public healthcare system.
The Institutional Review Board of IMSS hospitals
approved the present analysis.
Individual patient data were recorded from January 2009
to February 2011, in a standardised structured case report
form (CRF), especially designed for the purpose of this
study. For each patient, we registered the use of medical
resources such as diagnostic tests, DMTs, drugs for
symptoms control, outpatient medical revisions, patientday hospitalisations associated with relapses, patient-day
intensive care unit hospitalisations and rehabilitation care.
Four DMT alternatives were evaluated in the present
report: (1) interferon beta (IFNb)-1a, 6 million units (MU);
(2) IFNb-1a, 12 MU; (3) IFNb-1b, 8 MU; and (4) glatiramer acetate. These alternatives are the most commonly
used in the Mexican Social Security Institute. The pattern
of resources use and direct costs were recorded for a
sample of 492 relapsing-remitting MS patients of Mexican
hospitals pertaining to the Mexican Social Security Institute. Only certified neurologists with experience in MS
diagnosis and management were responsible for the
healthcare of patients pertaining to this cohort. The main
study measures were institutional use of resources, costs of
care and annualised relapse rate. We included patients aged
18–70 years, with relapsing-remitting MS according to
123
TCj ¼
n
XÀ
Á
Qij à Ci ;
i¼1
where TC total costs during the simulated time frame,
Q resource units during the simulated time frame, and
C unitary cost of resource Q.
Statistical analysis
Parametric continuous variables are expressed as minimum
and maximum geometric means. Non-parametric continuous variables are expressed as medians. Categorical variables are expressed as percentages. To compare
quantitative variables distributed between two groups,
Student’s t test was performed in parametric distributions.
Chi square statistics (i.e., Pearson’s Chi square or Fisher’s
exact test, as corresponded) were used to compare nominal
variables in bivariate analyses, among two or more nominal
categories. Spearman’s test was used for the evaluation of
class correlations. All P values are two-sided and considered significant when P 0.05. SPSS v 17.0 software for
windows (SPSS, Inc, Chicago, IL, USA) was used for all
statistical calculations.
Results
A total of 492 patients (67 % women) with confirmed
diagnosis of relapsing-remitting MS were studied
(Table 1). All patients were treated with a DMT for at least

3. Acta Neurol Belg
1 year. The most frequently used DMT was glatiramer
acetate (n = 224, 45.5 %), followed by IFNb-1a 12 MU
(n = 111, 22.6 %), IFNb-1b 8 MU (n = 102, 20.7 %), and
IFNb-1a 6 MU (n = 55, 11.2 %). No differences were
found between groups of treatment with respect to demographic characteristics. Direct costs of each DMT option
are shown in Table 2. The interclass correlation between
cost of DMT and usage weight was non-significant
(Spearman’s rho = 0.800, P = 0.20).
The mean cost of each specialised medical consultation,
which included prescription filling, was €74.90 (US
$107.00), and each relapse had a mean cost of €2,505.97
(US $3,579.96). The economic burdens among DMT
groups were mainly due to costs of medical consultations,
medications used, hospital stay, rehabilitation costs, number of relapses, and cost of DMT option (Table 3). It is
important to highlight that differences in total number of
relapses between treatment groups were not necessarily a
result of intrinsic drug efficacy, since medical decisionmaking about the indication of a particular therapeutic
option was based on several factors, among them, patient’s
preference of the injection protocols and local availability
of each drug option. Figure 1 shows the proportion of
patients having at least one relapse per year by DMT, age
and gender. The corresponding annualised relapse rates per
100 persons-year for IFNb-1a 6 MU, IFNb-1a 12 MU,
IFNb-1b 8 MU and glatiramer acetate were 45.45, 46.84,
50 and 43.75 %, respectively (P = 0.76).
Annualised costs per patient for each therapeutic option
are depicted in Fig. 2. The main differences in costs by
treatment group were due to direct drug costs, since mean
individual costs per patient did not differ with respect to
relapses or use of institutional resources. Thus, the group of
glatiramer acetate represented the higher mean costs per
patient-year, when compared with the other therapeutic
options.
Discussion
The most important finding of the present report is that,
when equipotent DMTs are used in patients with comparable characteristics, the costs of DMTs determine the total
institutional expenses associated with care of patients with
Table 1 Characteristics of the 492 patients with relapsing-remitting multiple sclerosis
Characteristics
Option of disease-modifying therapy
Glatiramer acetate
(n = 224)
Age, median (range), years
IFNb-1a 6 MU
(n = 55)
IFNb-1a 12 MU
(n = 111)
IFNb-1b 8 MU
(n = 102)
39.6 (18–63)
42.3 (22–63)
39.3 (18–68)
40.0 (18–61)
B30 years, n (%)
40 (17.9)
9 (16.4)
17 (15.3)
20 (19.6)
31–40 years, n (%)
97 (43.3)
21 (38.2)
51 (45.9)
39 (38.2)
41–50 years, n (%)
50 (22.3)
8 (14.5)
30 (27.0)
27 (26.5)
51–60 years, n (%)
32 (14.3)
13 (23.6)
12 (10.8)
13 (12.7)
61–70 years, n (%)
5 (2.2)
4 (7.3)
1 (0.9)
3 (2.9)
Gender
Male, n (%)
Female, n (%)
Time since diagnosis, mean (range), years
Family history of multiple sclerosis
None, n (%)
Mother, n (%)
74 (33.0)
21 (38.2)
32 (71.2)
35 (65.7)
150 (67.0)
34 (61.8)
79 (29.8)
67 (34.3)
3.8 (1–8)
4.3 (1–11)
6.2 (1–12)
8.7 (1–8)
236 (96.7)
53 (93.4)
109 (98.2)
98 (96.1)
1 (0.4)
0 (0)
0 (0)
0 (0)
Father, n (%)
0 (0)
0 (0)
0 (0)
0 (0)
Sibling, n (%)a
3 (1.2)
0 (0)
0 (0)
2 (1.9)
Other, n (%)
4 (1.6)
2 (3.6)
2 (1.8)
2 (1.9)
Glatiramer acetate, n (%)
2 (0.9)
28 (50.9)
36 (32.4)
2 (1.9)
IFNb-1a 6 MU, n (%)
3 (1.3)
2 (3.6)
2 (1.8)
5 (4.9)
IFNb-1a 12 MU, n (%)
5 (2.2)
1 (1.8)
28 (25.2)
2 (1.9)
19 (8.5)
4 (7.3)
30 (29.4)
5 (4.9)
Previous disease-modifying treatments
IFNb-b 8 MU, n (%)
IFNb Interferon beta, MU million units
a
No affected twins were observed
123

4. Acta Neurol Belg
Table 2 Institutional costs per patient, across alternatives of disease-modifying therapies
Variable
Unitary cost
Units per month
30
Glatiramer acetate
€40.80 (US $58.28)
IFNb-1a 6 MU
€132.30 (US $189.00)
IFNb-1a 12 MU
€68.00 (US $97.14)
IFNb-1b 8 MU
€76.43 (US $109.19)
Costs per month of treatment
Costs per year of treatment
€1,223.94 (US $1,748.49)
€14,687.35 (US $20,981.93)
€529.21 (US $756.02)
€6,350.60 (US $9,072.29)
12
€815.96 (US $1,165.66)
€9,791.56 (US $13,987.95)
12
€917.17 (US $1,310.24)
€11,006.02 (US $15,722.89)
4
Sale prices to the Mexican Social Security Institute (Instituto Mexicano del Seguro Social, IMSS)
IFNb Interferon beta, MU million units
Table 3 Annual relapses according to disease-modifying therapy
Age
Crude number of annual
relapses
Number of patients with at least 1 relapse per
year
Percentage of patients with at least 1 relapse
per year
Men
Men
Women
Men
Women
Women
Glatiramer acetate
B30 years
10
22
8
14
3.57
6.25
31–40 years
18
38
12
31
5.35
13.83
41–50 years
6
16
6
11
2.68
4.91
51–60 years
5
14
4
8
1.79
3.57
61–70 years
0
6
0
4
0.00
1.79
B30 years
2
4
2
4
3.63
7.27
31–40 years
3
7
3
7
5.45
12.72
41–50 years
0
2
0
2
0.00
3.63
51–60 years
0
8
0
5
9.09
0.00
61–70 years
2
0
2
0
3.63
0.00
B30 years
31–40 years
13
5
4
18
8
4
4
16
7.21
3.60
3.60
14.41
41–50 years
5
10
5
9
4.50
8.11
51–60 years
1
8
1
5
0.90
4.50
61–70 years
0
0
0
0
0.00
0.00
IFNb-1a 6MU
IFNb-1a 12MU
IFNb-1b 8MU
B30 years
3
14
3
9
2.94
8.82
31–40 years
10
16
9
14
8.82
13.72
41–50 years
3
8
1
8
0.98
7.84
51–60 years
7
2
5
2
4.90
1.96
61–70 years
0
0
0
0
0.00
0.00
No statistically significant differences were observed between treatment groups with respect to the annualised relapse rates (P = 0.76)
IFNb Interferon beta, MU million units
relapsing-remitting MS, in the Mexican Social Security
Institute. The clinical efficacy among DMTs was highly
comparable, but significant differences in annual healthcare
costs were observed across treatment groups.
In this study glatiramer acetate was the most commonly
used DMT, but it was also the most expensive. This contrasts with information derived from developed nations
[13–15], which evidences that large variations in local
123
market prices exist among countries, possibly originating
significant different results of economic evaluations of MS
burden for the healthcare system [16]. Nevertheless, few
studies exist about the economic burden of MS in low- to
middle-income countries [2], which may hamper comparisons with information derived from developed nations.
Different approaches generate distinct healthcare costs
when facing the MS burden [17–23]. Hence, the different

5. Acta Neurol Belg
Fig. 1 Percentage of patients
with at least 1 relapse per year,
by age and gender, and
according to disease-modifying
therapy alternative. IFNb
interferon beta, MU million
units
Fig. 2 Mean institutional costs
per patient-year according to
disease-modifying therapy
alternative
players of the healthcare system should evaluate their
feedback strategies that fuel improvement. In this sense,
the least costly alternatives providing the best therapeutic
responses in an adequate circumstance should be privileged
over the others [19].
The main limitation of this study is its retrolective nature that could overlook minor but significant institutional
costs. A stratification of MS patients according to their
disability (i.e., EDSS) to determine direct and indirect costs
of care was not performed [18]; nonetheless, the main
objective of the present report was to compare the healthcare costs according to DMTs, and the total annual cost per
MS patient was primarily determined by DMT option.
Since this study is not a cost-effectiveness analysis, no
sensitivity analysis or willingness-to-pay thresholds were
performed. Moreover, no estimations of productivity loss
or impact on quality of life were done, and the apparent
imbalances associated with DMTs costs were not evaluated
in terms of cost-benefit ratios. Based on the present results,
a cost-effective analysis taking into account the particular
circumstances of the Mexican Healthcare System is
warranted.
In conclusion, the annual institutional expenditure of
MS is mainly a function of the costs of DMT. Annual
relapses across treatment alternatives are comparable;
nevertheless, it is very important to evaluate the balance
between costs and benefits, especially in the light of new
costly but highly effective therapeutic options [24].
Acknowledgments This study received financial support by Novartis, Mexico. The company was involved in study design and analysis, but had no role in the selection of patients, data capture,
assignations of costs or resources use, the final approval of this article
or the decision for submission to publication.
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