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Original Paper

Eur Neurol 2011;65:59–67 Received: April 2, 2010


Accepted: November 29, 2010
DOI: 10.1159/000323216
Published online: January 4, 2011

Adherence to Disease-Modifying Therapies in


Spanish Patients with Relapsing Multiple
Sclerosis: Two-Year Interim Results of the Global
Adherence Project
E. Arroyo a C. Grau a C. Ramo-Tello b J. Parra a O. Sánchez-Soliño a  
         

on behalf of the GAP Study Group
a
  Biogen Idec Iberia SL, Madrid, and b Hospital Universitario Germans Trias i Pujol, Badalona, Spain
 

Key Words Introduction


Disease-modifying therapy ⴢ Patient adherence ⴢ
Multiple sclerosis ⴢ Patient education Multiple sclerosis (MS) is a chronic and debilitating
disease that can partly be controlled with long-term use
of disease-modifying therapy (DMT). The DMTs on the
Abstract market on initiation of the Global Adherence Project
The post-marketing international Global Adherence Project (GAP) were intramuscular (IM) interferon-␤ (IFN␤)-1a
investigated adherence to disease-modifying therapy for re- (Avonex쏐), subcutaneous (SC) IFN␤-1a 22 ␮g (Rebif 쏐22),
lapsing-remitting multiple sclerosis. We report adherence SC IFN␤-1a 44 ␮g (Rebif 쏐 44), IFN␤-1b (Betaferon쏐),
data from the first 2 years in the Spanish subset of patients and glatiramer acetate (Copaxone쏐). The WHO defines
(n = 254 at baseline). The overall adherence rate was 85.4%. treatment adherence as compliance (that is, taking the
Patients taking intramuscular (IM) interferon-␤ (IFN␤)-1a medication according to the prescribed dosing regimen)
were significantly more adherent (96.4%) compared with and persistence with dosing (taking the medication
patients taking subcutaneous (SC) IFN␤-1a 22 ␮g (79.1%; p = throughout the entire indicated treatment period), and
0.0064), SC IFN␤-1a 44 ␮g (79.6%; p = 0.0064) and glatiramer affirms that lack of adherence contributes to reduced ef-
acetate (82.7%; p = 0.0184). At year 1 (n = 142), the overall ficacy in the treatment of chronic diseases [1]. Between 19
adherence rate was 86.6%. Patients on IM IFN␤-1a were sig- and 39% of patients with MS stop treatment with IFN␤
nificantly more adherent than patients on SC IFN␤-1a 22 ␮g within 3 years [2, 3]. Moreover, it has been reported that
(93.9 vs. 66.7%; p = 0.0251). At year 2 (n = 131), the overall ad- between 10 and 20% of patients who stop treatment do so
herence rate was 82% (87.5% for IM IFN␤-1a, 80.0% for SC in the first 6 months [3, 4].
IFN␤-1a 22 ␮g, 77.8% for SC IFN␤-1a 44 ␮g, 85.2% for IFN␤- In clinical trials, the patients undergo close follow-up
1b, and 80.0% for glatiramer acetate). In conclusion, adher- and regular examinations and are encouraged to contin-
ence remained high among all disease-modifying therapies ue treatment, while the healthcare professionals are mon-
over the first 2 years of the study and was significantly high- itored by the sponsor. In observational studies, in con-
er for IM IFN␤-1a, at visit 1, compared with SC IFN␤-1a. trast, monitoring of adherence is variable and may be in-
Copyright © 2011 S. Karger AG, Basel fluenced by several factors to which patients in clinical
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© 2011 S. Karger AG, Basel Estefanía Arroyo


0014–3022/11/0652–0059$38.00/0 Departamento Médico, Biogen Idec Iberia
Fax +41 61 306 12 34 Paseo de la Castellana, 41-3a, ES–28046 Madrid (Spain)
E-Mail karger@karger.ch Accessible online at: Tel. +34 91 310 7142, Fax +34 91 310 7111
www.karger.com www.karger.com/ene E-Mail estefania.arroyo @ biogenidec.com
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trials are not exposed, thus allowing a more faithful eval- The questionnaire data were compared with the medical
uation of clinical practice [5–7]. records by monitoring visits conducted by an independent com-
pany. Patients and neurologists filled out the questionnaires in-
Patients are often wary of starting DMT because of the dependently and without any interaction in a single annual visit.
side effects and chronic administration regimens with The Neurologist Questionnaire comprised 13 questions that in-
frequent injections [6]. It has been observed that DMT cluded information on details of the place of work (infrastructure,
might not be effective in those patients with a poor level roles of nurses and/or other professions involved), questions on
of adherence in the long term [2]. According to different the information provided to the patients about treatment (mech-
anism of action, adverse reactions, administration method) and
authors, the main factors that contribute to whether the questions about the relevance of adherence and factors that might
patient is adherent are related to perceived lack of effica- influence it. The patient questionnaire collected information on
cy, lack of information or too complex information, false the point of view of the patients about the care received (health-
hopes of improvement in the disease, problems adminis- care staff involved, value of the different visits and education that
tering treatment (such as fear of needles or self-injections) was given during these visits), personal view of the current MS
therapy and its complications, adherence to drugs for treating MS
and sociocultural factors [8, 9]. in the last 4 weeks and sources of support that might influence
Few studies have compared adherence among DMTs patient adherence. In each patient questionnaire, the healthcare
currently available for MS [6, 10]. The international GAP worker completed the first 10 questions about disease duration,
study, an observational, multicenter, phase IV, post- degree of disability, treatment, and history of relapses and treat-
marketing, retrospective, cross-sectional study, included ment.
2,648 patients with relapsing-remitting MS (RRMS) in 22 Statistical Analysis
countries [5]. A global adherence rate of 75% was found, A descriptive analysis was undertaken, along with a correla-
with forgetting to inject the factor that most contributed tion analysis of the variables or factors that influence adherence.
to lack of adherence (50.2%). Continuous data were described using appropriate statistics:
In Spain and Portugal, a 5-year follow-up study is be- mean and standard deviation, or median and range. Possible
group differences were analyzed by means of a parametric test
ing conducted to assess long-term adherence and the fac- (ANOVA) and a non-parametric one (Kruskal-Wallis test); cate-
tors that influence adherence in patients who were previ- gorical data were presented by frequency distribution and per-
ously enrolled in the GAP study [5]. In this article, we centage for each group of DMT.
report the results of the first 2 years of the study in Spain. Adherence rates were estimated and compared between IM
IFN␤-1a and the other DMTs. The analyses were done using two-
tailed tests with a type-I error (␣-type error) of 0.05.
Frequencies and percentages for ‘good treatment adherence’
Patients and Methods versus ‘lack of treatment adherence’ variable were analyzed, and
possible differences between treatment environments were inves-
This is an observational, multicenter, phase IV, post-market- tigated using the ␹2 test or the Fisher exact test.
ing, retrospective, cross-sectional study of patients with RRMS Factors potentially related to treatment adherence were ana-
who attend annual visits for 5 years. The secondary objectives in lyzed using a log-rank test. The dependent variable (adherence)
Spain included assessment of patient satisfaction and physician was analyzed according to treatment satisfaction, effectiveness of
satisfaction with the new presentation of IM IFN␤-1a and the current treatment, ease of treatment administration, treatment
health-related quality of life – these data will be published sepa- tolerability, effect on delaying disease progression and improve-
rately. ment in MS symptoms, in addition to sociodemographic vari-
Non-adherence was defined as missing an injection or dose ables.
modification in the 4 weeks prior to completing the survey. The
patients signed an informed consent both at the start of the study
and for follow-up, and the ethics committees approved the initial
study in 18 centers and the follow-up study in 15. Results
The study included adult patients with RRMS in treatment for
at least 6 months prior to inclusion in the study with one of the The Spanish part of the GAP study included 254 pa-
DMTs available at the start of the study (in accordance with the
prescribing information and the judgment of the MS Assessment tients at the baseline visit, 142 after 1 year of follow-up
Committee in each Spanish autonomous region, if applicable). (visit 1) and 131 after 2 years of follow-up (visit 2). The
Each center aimed to include the same number of patients in baseline demographic characteristics are presented in ta-
each of the treatment groups. For each treatment group, it was ble 1. Significant differences were only found in the gla-
planned to include at least 3 patients and at most 6. The maxi- tiramer-acetate-treated group (lower mean age, shorter
mum number of patients included per center was therefore 30.
Patients were included consecutively as they attended their regu- treatment duration and shorter disease duration), in the
lar follow-up appointment and gave their consent to participate SC IFN␤-1a 44-␮g-treated group (shorter treatment dura-
in the study. tion) and the IFN␤-1b-treated group (greater disease dura-
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Table 1. Baseline patient characteristics

IM IFN␤-1a IFN␤-1a 22 ␮g IFN␤-1a 44 ␮g IFN␤-1b GA Overall


(n = 56) (n = 43) (n = 54) (n = 49) (n = 529) (n = 254)

Mean age 8 SD, years 38.8810.1 37.289.0 38.4810.6 40.1811.0 35.188.2a 37.989.9
Sex, % female 78.2 62.8 68.5 67.3 73.1 70.4
Mean number of relapses in prior year, % patients
0 66.1 67.4 55.6 69.4 57.7 63.0
1 28.6 23.3 24.1 20.4 15.4 22.4
2 5.4 4.7 11.1 10.2 17.3 9.8
>3 0 4.7 9.3 0 9.6 4.7
Median (range)
Current treatment duration 40.5 (6–108) 40.0 (6–120) 24.0 (6–60)b 45.0 (6–124) 15.0 (6–42)c 28.0 (6–124)
Disease duration 8.0 (1–33) 7.0 (1–17) 5.0 (1–34) 7.0 (1–37)d 6.0 (1–16)e 6.0 (0–37)

GA = Glatiramer acetate; IFN = interferon; IM = intramuscular.


ap = 0.01 vs. SC IFN␤-1b. b p = 0.0009 vs. IM IFN␤-1a; p = 0.0012 vs. IFN␤-1a 22 ␮g; p = 0.0003 vs. IFN␤-1b. c p < 0.0001 vs. IM
IFN␤-1a, IFN␤-1a 22 ␮g, IFN␤-1b; p = 0.02 vs. IFN␤-1a 44 ␮g. d p = 0.05 vs. IFN␤-1a 44 ␮g. e p ≤ 0.05 vs. IM IFN␤-1a and IFN␤-1b.

Table 2. Reasons for lack of adherence at baseline: treatment comparison

Reason, % patients IM IFN␤-1a IFN␤-1a 22 ␮g IFN␤-1a 44 ␮g IFN␤-1b GA


(n = 56) (n = 43) (n = 54) (n = 49) (n = 52)

Forgotten 0 16.3 11.1 12.2 13.5


Injection-related reasons 3.6 4.7 7.4 4.1 11.6
Flu-like symptoms 0 0 0 2.0 1.9
Weakness 0 0 0 2.0 1.9
Depression 0 0 1.9 2.0 0
Fatigue 0 0 0 2.0 1.9
Medication not collected 0 0 3.7 0 0
Did not feel the need to inject 0 2.3 0 0 0
No help for administration 1.8 0 0 0 0
Not confident about the treatment benefits 0 0 0 0 1.9

GA = Glatiramer acetate; IFN = interferon; IM = intramuscular.

tion). The median time on current therapy was 28.0 months ence at baseline are summarized in table 2. The overall
and the median disease duration was 2.3 years (table 1). adherence rate at visit 1 was 86.6% and patients receiving
IM IFN␤-1a were significantly more adherent than those
Patient Questionnaire receiving SC IFN␤-1a 22 ␮g (93.9 vs. 66.7%; p = 0.0251).
Adherence Rate At visit 2, the overall adherence rate was 82.4%; this was
The overall adherence rate was 85.4% at baseline and greater for IM IFN␤-1a (87.5%) versus the remaining
82.4% after 2 years (fig. 1). At the baseline visit, after al- DMTs (SC IFN␤-1a 22 ␮g: 80%; SC IFN␤-1a 44 ␮g
most 3 years on treatment, patients receiving IM IFN␤-1a (77.8%); IFN␤-1b (85.2%) and glatiramer acetate (80%).
were significantly more adherent (96.4%) than those re- After 2 years, 30.3% of all patients continued with the
ceiving SC IFN␤-1a 22 ␮g (79.1%; p = 0.0064), SC IFN␤- same treatment as at baseline; 43% continued with IM
1a 44 ␮g (79.6%; p = 0.0064) and glatiramer acetate IFN␤-1a, a significantly higher percentage (p = 0.0103)
(82.7%; p = 0.0184) (fig. 2). The reasons for lack of adher- than with the other DMTs (fig. 3).
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50
Non-adherent a
Adherent 45 43
100
40
14.6 13.4 17.6
90
35 32.3
80
30

Patients (%)
26.7 26.7
70
25
60
Patients (%)

20 17.5
50
15
85.4 86.6 82.4
40
10
30
5
20
0

IM IFN␤-1a

GA
IFN␤-1a 22

IFN␤-1b
IFN␤-1a 44
10

0
Baseline visit Visit 1 Visit 2

Fig. 1. Overall adherence rate at baseline and visits 1 and 2. Fig. 3. Percentage of patients who continued with the same treat-
ment at 2 years. a p = 0.0103 versus other treatments (abbreviations
as in fig. 2).

Baseline Visit 1 Visit 2


100 96.4 93.9
90.9
87.5 c 87.5 87.8 d
90 a 85.2 85.4 86.6
82.7 82.4
79.1 80 79.6 80
77.6 77.8
80
b

70 66.7
Adherence (%)

60

50

40

30

20

10

0
IM IFN␤-1a IFN␤-1a 22 IFN␤-1a 44 IFN␤-1b GA All

Fig. 2. Adherence rates by treatment at baseline and visits 1 and 2. GA = Glatiramer acetate; IM = intramus-
cular; IFN = interferon. a p = 0.0064 vs. IM IFN␤-1a; b p = 0.0251 vs. IM IFN␤-1a; c p = 0.0064 vs. IM IFN␤-1a;
d p= 0184 vs. IM IFN␤-1a.
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Independence afforded by the
4.1
treatment

Number of times a week I have to


3.5
administer medication

My ability to self-administer
3.6
the medication

Availability of a self-injection device


3.7
for administration of my medication

Route of administration, e.g.,


3.7
intramuscular or subcutaneous

Nurse administers my treatment 2.2

Support of my nurse to teach me


self-administration of the therapy 3.5

Medication reduces MRI lesions 4

Medication has few adverse reactions 3.8

Medication is well known 3.6

Medication produces fewer


neutralizing antibodies 3.6

Medication delays disease


progression 4.6

Medication reduces my relapses 4.6

Cost of the medication 2.9

How the medication works 4.4

0 1 2 3 4 5
Least Most
Fig. 4. Considerations highlighted by the important important
patients at visit 2.

Factors Related to Lack of Adherence able to administer the injections. At years 1 and 2, the
Treatment-Related Factors. At baseline, the most com- most common reason for lack of adherence was injection-
mon reason cited for lack of adherence was forgetting related factors (89.5 and 72%, respectively), followed by
to inject (70.3%), followed by injection-related reactions forgetting to dose (42.1 and 32%, respectively). After 2
(43.2%) which encompassed the following aspects: tired years of treatment, among the injection-related reasons,
of self-injection, skin reactions, needle phobia, injection- being tired of injecting (28%) stands out.
site pain, not feeling the need to inject and nobody avail-
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Tired of taking
injections

New relapses

Injection
frequency

Fatigue

Flu-like
symptoms Overall

IM IFN␤-1a

Pain at IFN␤-1a 22
injection site
IFN␤-1a 44

IFN␤-1b
Needle phobia
GA

Skin reaction

0 20 40 60 80 100
Fig. 5. Considerations highlighted by the Patients (%)
neurologist at visit 2 (abbreviations as in
fig. 2).

The considerations with the highest score for the pa- 13% of the cases, the patient did not take any decision
tients at 2 years when the MS treatment is chosen, on a about treatment), whereas in the second year, the deci-
scale of 0–5 were: medication delays disease progression sion was shared equally.
(4.61), medication reduces relapses (4.5), how the medica- Sociocultural Factors. At the baseline visit, 36% of the
tion works (4.3) and the independence afforded by the patients worked full-time and 16% were retired or receiv-
treatment (4.1) (fig. 4). ing assistance for MS. At 2 years, 32.2% of the patients
Factors Related to the Healthcare Provider. The neu- were working full-time versus 26.3% who were retired or
rologists and nurses of adherent patients saw the patients receiving assistance for MS at the baseline visit. Most pa-
more often and more regularly both at the baseline visit tients were living with their spouse/partner or family
(89.1 and 25.7%) and at 2 years (99 and 31%), respectively. (parents or children) both at the baseline visit and at 2
Treatment decisions on the type of DMT that the pa- years.
tient was to receive was an activity shared between the The main sources of patient support at the start and
neurologist and the patient; however, at the start of the after 2 years of the study were, respectively: family (87
study, the neurologists’ decision had greater weight (in and 85.8%), spouse/partner (84.8 and 83.6%), physician
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Table 3. Time dedicated to the consultation with an MS patient at Among the support staff for the neurologist in clinical
baseline and visits 1 and 2 practice at the baseline visit and at 2 years, of note were
the nurses (83.3 and 85.7%), neuropsychologist (44.4 and
Diagnosis of Start of Routine
the disease treatment follow-up visits 71.4%), the physiotherapeutist (27.8 and 50.0%), and the
collaborating physician (50.0 and 42.9%).
Neurologist
Baseline visit 49.17% 35.83% 21.67%
Visit 2 50.71% 35.36% 20% Discussion
Nurse
Baseline visit 30.59% 49.12% 12.85%
Visit 2 12.65% 30.71% 12.14% The international GAP study [5] is being extended in
Spain for 5 years, and an interim analysis has been per-
formed at 2 years. At 2 years, an inflexion point in adher-
ence was observed, with a decrease across all treatments.
The adherence rate has remained high among all DMTs
for the first 2 years of the study, and was significantly
and nurse (80.6 and 77.4%), friends (69.6 and 69.2%), oth- higher with IM IFN␤-1a compared to other DMTs after
er healthcare workers (50.2 and 54.8%), and religious be- a median of more than 3 years of treatment. The number
liefs (49.4 and 48.4%). of patients who continued with the same treatment after
2 years was significantly higher with IM IFN␤-1a versus
Neurologist Questionnaire the other DMTs.
Adherence Rate The results of the baseline visit of the GAP study in
The estimated overall adherence according to the neu- Spain are consistent with the results from the interna-
rologist at baseline and visit 2 was 87.3 and 79.7% (SC tional study [5], with an overall adherence rate more than
IFN␤-1a: 93.9 and 90.9%; SC IFN␤-1a 22 ␮g: 88.5 and 10% higher (75% in the international GAP study [5] vs.
81.7%; SC IFN␤-1a 44 ␮g: 85.0 and 80.0%; IFN␤-1b: 82.8 85.4% in the Spanish GAP study). The distribution of the
and 75.4%, and glatiramer acetate: 86.5 and 71.1%, re- adherence rates in all treatments is also greater in the
spectively). Spanish GAP study. At the baseline visit, among factors
inherent to the medication, forgetting to inject was the
Factors Related to Lack of Adherence most common in both studies. Differences were found
Treatment-Related Factors. After 2 years of treatment, between the healthcare-provider-related and sociocul-
among the reasons related to lack of adherence, the neu- tural factors. At the baseline visit, unlike the internation-
rologists highlighted the development of new relapses al GAP study [5], no significant differences were found
(66.8%) (fig. 5). regarding sex and level of education of the patients. The
For the neurologist, the 5 attributes that were most involvement of the nurse in the follow-up of the patients
important for discussing with the patient when offering showed no changes between the baseline visit and visit 2,
treatment for MS at the baseline visit and visit 2 were ef- remaining steady at 12% (table  3). In contrast, after 2
fectiveness at preventing relapses (94.4 and 92.9%, re- years, an increase in multidisciplinary follow-up of the
spectively) and disease progression (77.8 and 92.9%, re- patients in the form of incorporation of neuropsycholo-
spectively), factors related to adverse effects of treatment gists and physiotherapists was detected compared to the
(88.9 and 92.9%, respectively), frequency of administra- baseline visit. In view of the decrease in overall adherence
tion (44.4 and 42.9%, respectively), administration skill rate at visit 2, it might be necessary to review the role of
(44.4 and 50.0%, respectively) and disease activity ac- nursing staff in follow-up. Of note is the neurologists’
cording to magnetic resonance imaging (44.4 and 42.9%, perception of adherence, which is almost 3 points lower
respectively). than the real patient adherence. This perceived adherence
Factors Related to the Healthcare Provider. At the base- is only higher in the case of IM IFN␤-1a and SC IFN␤-1a
line visit and visit 2, the time dedicated by the neurologist 44 ␮g, suggesting that the neurologists overestimate real
to diagnosis of the disease, starting treatment, and rou- adherence in their patients with these treatments and
tine follow-up visits was similar, whereas the nurse dedi- dedicate them less time. After 2 years of follow-up, the
cated more time to the patients at the baseline visit com- partner, family members and religious beliefs continue to
pared to follow-up visits (table 3). play an important role.
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One of the limitations of this study is the way adher- with these factors that influence adherence, maintaining
ence is measured. Observational studies usually have to fluid dialogue with the patient and monitoring aspects
rely on measures susceptible to bias such as patient recall related to the safety of the drug. Although these are dy-
of missed doses in the past 4 weeks, as is the case in the namic factors, if they are managed effectively, there
present study. Given that patients with MS can experi- would be greater emphasis on patient education and long-
ence progressive cognitive decline [11], recall could be in- term adherence would be enhanced.
fluenced by memory decline. In English-speaking coun- The results of the Spanish GAP study, along with the
tries of the international GAP study [5], the MS Neuro- studies conducted until present [6, 10], confirm the need
psychological Screening Questionnaire was administered to be aware of the importance of adherence to MS therapy
to patients; unfortunately, these data were not available in with DMTs. The use of questionnaires enabled assessment
our subpopulation. It is not clear how a decline in cogni- of the views of the neurologists and patients on factors
tive function would affect recall of adherence, that is, that may influence adherence. This shows that in general,
whether patients with cognitive decline are more likely to adherence in Spain is higher than in other countries and
overestimate or underestimate adherence. We do note, remains high after 2 years of follow-up, remaining above
however, a greater apparent difference in the neurolo- the international baseline level despite a decrease of 3%.
gist’s assessment of adherence (87.3% at baseline vs. 79.7% Follow-up of the GAP study in Spain has enabled us to
after 2 years) as compared to the patient assessment (85.4 verify the importance of certain health and sociocultural
vs. 82.4%). Cognitive decline may also have a direct influ- factors described previously, as well as aspects of quality
ence on adherence [12]. of life and patient and neurologist satisfaction, which will
Another of the limitations of this study is the loss to be published separately. In Spain, of particular note is the
follow-up (48.4%) either due to personal decision of the support of the partner, family and healthcare staff (neu-
neurologist (in 1 center) or due to the decision of the cen- rologist, nursing staff) as factors that have a positive influ-
ters themselves (in 2 centers). This resulted in a loss of ence on treatment adherence. After 2 years of follow-up,
statistical power making a ␤-type error possible. The multidisciplinary staff such as neuropsychologists and
groups were fairly homogeneous at baseline. Certain sig- physiotherapists played an increasing role in the care of
nificant differences were only found in the glatiramer ac- patients with MS. Neurologists were also found to remain
etate group, the SC IFN␤-1a 44 ␮g group and the IFN␤- involved in patient follow-up. We believe that these factors
1b group. These differences can be explained by the contribute positively to the high adherence to DMTs seen
shorter time on the market of glatiramer acetate and SC in this country. The positive correlation of IM IFN␤-1a
IFN␤-1a 44 ␮g, and the longer time on the market in the with adherence is due, we believe, to the lower frequency
case of IFN␤-1b. However, at the different visits, adjust- of injection compared to other DMTs. We wish to high-
ments between groups were not made for baseline values, light that in 2 years of follow-up, forgetting to inject went
essentially because of the obvious decrease in sample size. from being the principal reason for poor adherence to sec-
Other factors that might complicate analysis of the study ond place (after injection-related factors), with a 38.3% de-
include the lack of randomization, differences in treat- crease. We therefore believe that the greater awareness
ment duration and withdrawals or changes in treatment, among healthcare staff and patients in the study is having
which are typical occurrences in observational studies. a positive effect on remembering to inject the medication.
The present study has shown that the therapeutic op- To date, as far as we are aware, this is the only obser-
tion may directly affect adherence of an MS patient to vational study of adherence to DMTs that is being con-
DMT. ducted in MS patients in Spain. Observational studies
The most common reasons for lack of adherence were with long-term follow-up have the added value of being
forgotten doses and injection-related factors, with such able to compare the results of clinical trials with daily
factors predominating during follow-up (particularly clinical practice and analyze aspects relating to effective-
getting tired of injection), probably due to the treatment ness, which are not studied in clinical trials. This has
duration and chronic nature of the disease. prompted us to draw up adherence questionnaires which
Frequency of drug administration, side effects of the will be published separately. We consider it necessary to
medication and the patients’ perception of treatment ef- develop tools that help healthcare staff assess adherence
ficacy were treatment-related factors found to affect lack to DMTs in order to anticipate any problems that patients
of adherence. These factors should be considered when might have with specific therapeutic regimens and DMTs
making therapeutic choices. Healthcare staff should deal in general. This would help optimize the outcomes of
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current DMTs. These questionnaires would also provide nau de Vilanova, Lleida); Lacruz F., Bujanda M. (H. De Navarra,
healthcare staff with the most appropriate measures for Pamplona); de Castro P. (Clínica Univ. De Navarra (Pamplona);
Marzo E. (Complejo H. San Millán-San Pedro, Logroño); Hernán-
improving follow-up of therapy in MS patients, particu- dez M.A., González M. (H. Ntra. Sra. de Candelaria, Tenerife); de
larly in those at high risk of lack of adherence and in those Andrés C., Martínez M. (H. Universitario Gregorio Marañón,
with longer disease and treatment durations, in whom Madrid); Izquierdo G. (Complejo Hospitalario Virgen Macarena,
adherence has been found to be poorer. Sevilla); Sánchez F., Agüera E., Sánchez V. (H. Reina Sofía de Cór-
In conclusion, in the Spanish GAP study, the overall doba, Córdoba); Guerrero M. (H. Univer. San Cecilio, Granada);
Arnal C. ( H. Universitario Virgen de las Nieves, Granada); Bowa-
rate of adherence remained high over the 2 years of fol- kin D., Renedo F. (Hospital Universitario ‘Del Río Hortega’, Val-
low-up reported here, and higher than the baseline ad- ladolid); Cacho J. (Complejo Asistencial de Salamanca, Salaman-
herence recorded in the international GAP study [5]. It ca); Yusta A. (H. Univer. De Guadalajara, Guadalajara); Pérez A.
was highest with IM IFN␤-1a; this difference was signif- (H. General Universitario de Alicante, Alicante); Belenguer A. (H.
icant at the baseline visit (after nearly 3 years on therapy) General de Castellón, Castellón).
compared with other DMTs. It would be appropriate to
strengthen the role of nursing staff in the follow-up of
patients receiving DMTs. Treatment adherence is also Acknowledgments
improved if both patients and healthcare providers are The GAP study was sponsored by Biogen Idec. Four of the au-
aware of its importance. thors (E.A., C.G., J.P., O.S.S.) worked for Biogen Idec. C.R.-T. has
received lecture fees and grant support from Bayer-Schering, Bio-
gen Idec, Merck-Serono, and Teva Neuroscience. We are indebted
Appendix 1 to the GAP investigators who are listed in Appendix I. Editorial
support was provided by Dr. Gregory Morley (funded by Biogen
GAP Investigators Idec Iberia). The authors would like to thank all the investigators
Ramo C., Grau L. (H. Universitario Germans Trias i Pujol, and patients who participated in the study.
Badalona); Roquer J., Munteis E., Martínez E. (H. Del Mar, Bar-
celona); Ramió i Torrento L.L., Merchán M. (H. Universitario de
Girona Dr. Josep Trueta, Girona); Brieva L. (H. Universitario Ar-

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