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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. Macı́as-Islas • Isaac F. Soria-Cedillo • Merced Velazquez-Quintana •

Victor M. Rivera • Verónica 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 relapses, intensive care and rehabilitation. Four groups
patients with multiple sclerosis (MS) in low- to middle- were defined according to DMT alternatives: (1) interferon
income nations. The purpose of this study was to describe beta (IFNb)-1a, 6 million units (MU); (2) IFNb-1a, 12MU;
the economic burden associated with care of Mexican (3) IFNb-1b, 8MU; and (4) glatiramer acetate. All patients
patients with relapsing-remitting MS in a representative received DMTs for at least 1 year. The most frequently
sample of the largest institution of the Mexican public used DMT was glatiramer acetate (45.5 %), followed by
healthcare system. We analysed individual data of 492 IFNb-1a 12MU (22.6 %), IFNb-1b 8MU (20.7 %), and
patients (67 % women) with relapsing-remitting MS reg- IFNb-1a 6MU (11.2 %). The mean cost of a specialised
istered from January 2009 to February 2011 at the Mexican medical consultation was €74.90 (US $107.00). A single
Social Security Institute. Direct costs were measured about relapse had a mean total cost of €2,505.97 (US $3,579.96).
the use of diagnostic tests, disease-modifying therapies No differences were found in annualised relapse rates and
(DMTs), symptoms control, medical consultations, costs of relapses according to DMT. However, a significant
difference was observed in total annual costs according to
M. A. Macı́as-Islas (&) treatment groups (glatiramer acetate being the most
Jefe del Departamento de Neurologı́a, UMAE, Centro Médico expensive), mainly due to differences in unitary costs of
Nacional de Occidente, IMSS, Belisario Domı́nguez #1000, Col. alternatives. From the public institutional perspective,
Independencia Oriente, C.P. 44340 Guadalajara, Jal, Mexico
when equipotent DMTs are used in patients with compa-
e-mail: miguelangelmacias@hotmail.com
rable characteristics, the costs of DMTs largely determine
M. A. Macı́as-Islas the total expenses associated with care of patients with
Department of Neurosciences, Centro Universitario de Ciencias relapsing-remitting MS in a middle-income country.
de la Salud, Universidad de Guadalajara, Guadalajara, Jal,
Mexico
Keywords Costs of care  Glatiramer acetate 
I. F. Soria-Cedillo  V. I. Baca-Muro  E. A. Lemus-Carmona Healthcare  Interferon  Multiple sclerosis
Department of Health Economics, Novartis Mexico, Mexico
City, DF, Mexico

M. Velazquez-Quintana Introduction
Department Health Research, Hospital Regional #1, IMSS,
Chihuahua, Chi, Mexico Multiple sclerosis (MS) is a disabling neurodegenerative
disease caused by immune-mediated destruction of mye-
V. M. Rivera
The Maxine Mesinger MS Comprehensive Care Centre, Baylor linated central nerve fibres [1]. Most individuals experience
College of Medicine, Houston, TX, USA their first symptoms between the ages 20 and 40 years [2]
and as a consequence, it leads to high costs associated with
E. Chiquete
lost of productivity, employment and quality of life [3–5].
Department of Neurology and Psychiatry, Instituto Nacional de
Ciencias Médicas y Nutrición ‘‘Salvador Zubirán’’, Mexico City, On one hand, the introduction of new costly disease-
DF, Mexico modifying therapies (DMTs) may contribute to the

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Acta Neurol Belg

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

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Acta Neurol Belg

1 year. The most frequently used DMT was glatiramer of each drug option. Figure 1 shows the proportion of
acetate (n = 224, 45.5 %), followed by IFNb-1a 12 MU patients having at least one relapse per year by DMT, age
(n = 111, 22.6 %), IFNb-1b 8 MU (n = 102, 20.7 %), and and gender. The corresponding annualised relapse rates per
IFNb-1a 6 MU (n = 55, 11.2 %). No differences were 100 persons-year for IFNb-1a 6 MU, IFNb-1a 12 MU,
found between groups of treatment with respect to demo- IFNb-1b 8 MU and glatiramer acetate were 45.45, 46.84,
graphic characteristics. Direct costs of each DMT option 50 and 43.75 %, respectively (P = 0.76).
are shown in Table 2. The interclass correlation between Annualised costs per patient for each therapeutic option
cost of DMT and usage weight was non-significant are depicted in Fig. 2. The main differences in costs by
(Spearman’s rho = 0.800, P = 0.20). treatment group were due to direct drug costs, since mean
The mean cost of each specialised medical consultation, individual costs per patient did not differ with respect to
which included prescription filling, was €74.90 (US relapses or use of institutional resources. Thus, the group of
$107.00), and each relapse had a mean cost of €2,505.97 glatiramer acetate represented the higher mean costs per
(US $3,579.96). The economic burdens among DMT patient-year, when compared with the other therapeutic
groups were mainly due to costs of medical consultations, options.
medications used, hospital stay, rehabilitation costs, num-
ber of relapses, and cost of DMT option (Table 3). It is
important to highlight that differences in total number of Discussion
relapses between treatment groups were not necessarily a
result of intrinsic drug efficacy, since medical decision- The most important finding of the present report is that,
making about the indication of a particular therapeutic when equipotent DMTs are used in patients with compa-
option was based on several factors, among them, patient’s rable characteristics, the costs of DMTs determine the total
preference of the injection protocols and local availability 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 IFNb-1a 6 MU IFNb-1a 12 MU IFNb-1b 8 MU
(n = 224) (n = 55) (n = 111) (n = 102)

Age, median (range), years 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 (%) 74 (33.0) 21 (38.2) 32 (71.2) 35 (65.7)
Female, n (%) 150 (67.0) 34 (61.8) 79 (29.8) 67 (34.3)
Time since diagnosis, mean (range), years 3.8 (1–8) 4.3 (1–11) 6.2 (1–12) 8.7 (1–8)
Family history of multiple sclerosis
None, n (%) 236 (96.7) 53 (93.4) 109 (98.2) 98 (96.1)
Mother, n (%) 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)
Previous disease-modifying treatments
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)
IFNb-b 8 MU, n (%) 19 (8.5) 4 (7.3) 30 (29.4) 5 (4.9)
IFNb Interferon beta, MU million units
a
No affected twins were observed

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Table 2 Institutional costs per patient, across alternatives of disease-modifying therapies


Variable Unitary cost Units per month Costs per month of treatment Costs per year of treatment

Glatiramer acetate €40.80 (US $58.28) 30 €1,223.94 (US $1,748.49) €14,687.35 (US $20,981.93)
IFNb-1a 6 MU €132.30 (US $189.00) 4 €529.21 (US $756.02) €6,350.60 (US $9,072.29)
IFNb-1a 12 MU €68.00 (US $97.14) 12 €815.96 (US $1,165.66) €9,791.56 (US $13,987.95)
IFNb-1b 8 MU €76.43 (US $109.19) 12 €917.17 (US $1,310.24) €11,006.02 (US $15,722.89)
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 Number of patients with at least 1 relapse per Percentage of patients with at least 1 relapse
relapses year per year
Men Women Men Women Men 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
IFNb-1a 6MU
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
IFNb-1a 12MU
B30 years 13 4 8 4 7.21 3.60
31–40 years 5 18 4 16 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-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 market prices exist among countries, possibly originating
Institute. The clinical efficacy among DMTs was highly significant different results of economic evaluations of MS
comparable, but significant differences in annual healthcare burden for the healthcare system [16]. Nevertheless, few
costs were observed across treatment groups. studies exist about the economic burden of MS in low- to
In this study glatiramer acetate was the most commonly middle-income countries [2], which may hamper compar-
used DMT, but it was also the most expensive. This con- isons with information derived from developed nations.
trasts with information derived from developed nations Different approaches generate distinct healthcare costs
[13–15], which evidences that large variations in local when facing the MS burden [17–23]. Hence, the different

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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 circumstances of the Mexican Healthcare System is
feedback strategies that fuel improvement. In this sense, warranted.
the least costly alternatives providing the best therapeutic In conclusion, the annual institutional expenditure of
responses in an adequate circumstance should be privileged MS is mainly a function of the costs of DMT. Annual
over the others [19]. relapses across treatment alternatives are comparable;
The main limitation of this study is its retrolective nat- nevertheless, it is very important to evaluate the balance
ure that could overlook minor but significant institutional between costs and benefits, especially in the light of new
costs. A stratification of MS patients according to their costly but highly effective therapeutic options [24].
disability (i.e., EDSS) to determine direct and indirect costs
of care was not performed [18]; nonetheless, the main Acknowledgments This study received financial support by Nov-
artis, Mexico. The company was involved in study design and anal-
objective of the present report was to compare the health- ysis, but had no role in the selection of patients, data capture,
care costs according to DMTs, and the total annual cost per assignations of costs or resources use, the final approval of this article
MS patient was primarily determined by DMT option. or the decision for submission to publication.
Since this study is not a cost-effectiveness analysis, no
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