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Optimizing the long-term management of chronic migraine with onabotulinumtoxinA in real life

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Introduction: Management of chronic migraine is challenging. OnabotulinumtoxinA (OBT-A) is the only medication licensed for prevention of chronic migraine, and has been widely adopted in clinical practice. Limited data is available on its long-term use. Areas covered: Data from controlled trials are combined with available data on the long-term use of OBT-A in real-life studies, with information obtained in a recent survey among Italian headache centers, and the clinical experience of the authors. Six areas were identified as relevant to patients with chronic migraine: 1) definition of responders to OBT-A; 2) management of responders to OBT-A; 3) optimal timing of prophylaxis with OBT-A; 4) position of OBT-A in prevention of chronic migraine; 5) management of medication overuse, and 6) patient education. Expert commentary: This review provides an update on the latest evidence regarding the long-term use of OBT-A in chronic migraine and analyzes the critical issues in the decision-making process that emerge from the analysis of the literature and routine practice. A treatment algorithm is proposed for the adoption in the daily practice.
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November 2017 | Volume 8 | Article 5861
ORIGINAL RESEARCH
published: 03 November 2017
doi: 10.3389/fneur.2017.00586
Frontiers in Neurology | www.frontiersin.org
Edited by:
László Vécsei,
University of Szeged, Hungary
Reviewed by:
Cherubino Di Lorenzo,
Sapienza University, Italy
Marcelo M. Valença,
Universidade Federal de
Pernambuco, Brazil
*Correspondence:
Simona Guerzoni
simona.guerzoni@gmail.com
Specialty section:
This article was submitted to
Headache Medicine and Facial Pain,
a section of the journal
Frontiers in Neurology
Received: 01August2017
Accepted: 19October2017
Published: 03November2017
Citation:
GuerzoniS, PellesiL, BaraldiC,
CainazzoMM, NegroA, MartellettiP
and PiniLA (2017) Long-term
Treatment Benets and Prolonged
Efcacy of OnabotulinumtoxinA in
Patients Affected by Chronic Migraine
and Medication Overuse Headache
over 3Years of Therapy.
Front. Neurol. 8:586.
doi: 10.3389/fneur.2017.00586
Long-term Treatment Benets
and Prolonged Efcacy of
OnabotulinumtoxinA in Patients
Affected by Chronic Migraine
and Medication Overuse Headache
over 3Years of Therapy
Simona Guerzoni1*, Lanfranco Pellesi1, Carlo Baraldi1, Michela Maria Cainazzo1,
Andrea Negro2, Paolo Martelletti2 and Luigi Alberto Pini1,3
1 Headache and Drug Abuse Research Centre, Policlinico Hospital, Department of Diagnostic Medicine, Clinical and Public
Health, University of Modena e Reggio Emilia, Modena, Italy, 2 Regional Referral Headache Centre, Sant’Andrea Hospital,
Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy, 3 Center for Neuroscience and
Neurotechnology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena e Reggio Emilia,
Modena, Italy
Background: Chronic migraine (CM) affects about the 2% of the general population and
it has been recognized as one of the most-disabling conditions worldwide by the World
Health Organization. CM is often associated with the overuse of abortive medication,
which determines the worsening of headache itself and the development of a secondary
headache called medication overuse headache. The management of these associated
conditions is difcult, but a growing amount of evidence is pointing out the effectiveness
and the good safety prole of OnabotulinumtoxinA (OnabotA). Despite this, data on
OnabotA effects and safety in long-term use lack. The purpose of the present article
is to retrospectively assess the efcacy and safety of OnabotA in a cohort of chronic
migraineurs with drug overuse from the 18th month of treatment until the third year.
Materials and methods: 90 chronic migraineurs with medication overuse were enrolled
between January 2013 and February 2017. All patients were treated with OnabotA
according to PREEMPT dictates. Before every injection session the headache index, the
analgesic consumption, the visual analog scale for pain score, the 36-items short form
health survey questionnaire score, the 6-items headache impact test (HIT-6) score and
the Zung self-rating anxiety and depression scale scores were collected. Adverse events
were carefully registered. A simple linear regression was performed to explore the mean
changes in the abovementioned parameters for a single injection session and mean
comparison tests were performed using the one-way analysis of variance followed by
Tukey–Kramer post-hoc test.
Results: A signicantly improvement for a single injection was registered for all the
above-mentioned parameters. Headache index, analgesic consumption, visual analog
pain scale, and 6-items HIT-6 scores were signicantly lower than baseline from the
18th month of treatment onwards. The 36-items short form health survey question-
naire scores were signicantly higher than baseline at every injections session from the
2
Guerzoni et al. Three Years Therapy with OnabotA in Migraine
Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
18th months onwards. Zung scales did not change. No serious adverse events were
assessed and no adverse events-related drop-outs were seen.
Conclusion: OnabotA effectiveness and safety last until 3years of therapy, raising the
possibility of the use of this therapy even for many years in CM prevention.
Keywords: chronic migraine, OnabotulinumtoxinA, long-term treatment, quality of life, tolerance, headache,
medication overuse headache
demonstrated from the results of the Phase III Research
Evaluating Migraine Prophylaxis erapy (PREEMPT) study
(1012). Results from the PREEMPT 1 and 2 trials outpointed
a signicant higher reduction than placebo in the number of
headache and migraine days in the treated group at the 24th
week of treatment. is was also reected by a lower triptan
consumption despite a similar analgesic intake (10, 11). Notably,
OnabotA-treated group had a signicant higher reduction than
placebo group of the 6-items headache impact test (HIT-6)
score at all time points. Moreover, a signicantly lower number
of patients with a HIT-6 score higher than 60, that is with a sub-
stantial headache impact on their quality of life, was seen in the
treated group (12). Furthermore, all these studies outpointed the
better safety prole of OnabotA, which gave a drop-out rate not
signicantly dierent than placebo (1012). Even those articles
comparing OnabotA with other preventive treatments outpoints
that, besides a similar eectiveness, OnabotA better safety prole
is associated with a lower discontinuation rate and should be
chosen as rst-line therapy to improve patients adherence (13).
Despite this, it is still unclear if OnabotA eectiveness for CM
disease lasts even aer years and if its good safety prole is
maintained through time (14). In a previous study, our group has
already demonstrated the eectiveness and safety of OnabotA
until the 18th month of treatment in chronic migraineurs com-
plicated with MOH (15) and, to our knowledge, data regarding
OnabotA eectiveness until 36months are currently missing.
e aim of this retrospective study is to explore the safety and the
eectiveness of OnabotA, administered quarterly and following
the PREEMPT paradigm (16), from the 18th to the 36th month
of therapy in patients aected by CM complicated by MOH.
MATERIALS AND METHODS
Patients Selection
In Modena University headache and drug abuse center, a
retrospective study was performed on patients aected by CM
complicated with MOH according to the International classica-
tion of headache disorders-third edition-beta version (ICHD-
III-beta) (2) and received OnabotA injection as prophylaxis.
At April 2016, 134 patients were in treatment with OnabotA.
Forty-four patients were immediately excluded because their
poor compliance in properly lling the headache diary. Ninety
patients were considered eligible and enrolled between March
2016 and September 2017. Every patient failed, at least, three
drug preventive treatments and underwent a hospital detoxica-
tion therapeutic recovery before start OnabotA injections, which
were administered between January 2013 and February 2017.
Abbreviations: AC, analgesic consumption; BAI, Beck anxiety inventory; BDI,
Beck depression inventory; CI, condence intervals; CM, chronic migraine;
DB, double-blind; DASS-21, 21-items depression, anxiety and stress scale;
HDRS, Hamilton depression rating scale; HIT-6, six item headache impact test;
ICHD-III-beta, International classication of headache disorders-third edition,
beta version; U, Units; MADRS, Montgomery-Asberg depression rating scale;
MIDAS, migraine disability assessment questionnaires; MNHD, mean number
of headache days over 30days; MSQ, migraine-specic quality of life question-
naire; PHQ9, 9-items patient health questionnaire; PHQDM, Patient Health
Questionnaire depression module; PREEMPT, Phase III Research Evaluating
Migraine Prophylaxis erapy Trail; MOH, medication overuse headache;
OnabotA, OnabotulinumtoxinA; SF-36, short form health survey questionnaire;
VAS, visual analog scale for pain; ZUNG-A, Zung self-rating anxiety scale;
ZUNG-D, Zung self-rating depression scale.
INTRODUCTION
Chronic migraine (CM) is a common neurological disorder
aecting about the 2% of the general population (1). It is
characterized by over than 15 headache days per month, eight
of which presenting migraine features, for at least 3 months
(2). e recurrent and excruciating pain impacts negatively on
patients’ quality of life: chronic migraineurs are more frequently
depressed, less likely to be employed and have a lower socioeco-
nomic status than episodic migraineurs (3). Besides this, they
have also a higher rate of sanitary services use and, considering
the prevalence of this disease, CM is one of the greatest causes of
sanitary expenditure worldwide (4). Chronic migraineurs usu-
ally assume a large amount of symptomatic drugs to relief pain,
with the 73% of them overusing abortive medications, mainly
triptans and non-steroidal anti-inammatory drugs (NSAIDs):
this can paradoxically lead to the worsening of CM, generating
a secondary headache called medication overuse headache
(MOH) (2). MOH complicates CM management: besides head-
ache worsening, patients are exposed to a greater likelihood of
developing drugs-related AEs, mainly cardiovascular and gastro-
intestinal (5). Since this, the withdrawal of the overused drug is
mandatory to reduce headache severity and increase preventive
treatments eectiveness, which is even lower in patients aected
by MOH than in chronic migraineurs without MOH (6). e
higher therapeutic failure rate is not only due to the worse condi-
tions of MOH-suerers but also to the generally low adherence
toward prescribed treatments (7): the reduction of treatment
eectiveness along time and the incoming of drugs-related AEs
usually force patients to discontinue preventive medications (8).
Considering this, for a good therapeutic response is crucial to
have a preventive therapy able to reduce pain with mild AEs,
maintaining its eectiveness and safety on long-time periods
(9). OnabotulinumtoxinA (OnabotA) eectiveness was clearly
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Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
Injection procedures strictly followed PREEMPT protocol items:
155 U of OnabotA were regularly injected every 3months in 31
sites of head, neck, and shoulders by an expert clinician (16).
Patients were allowed to take abortive medications without any
restriction, whereas no more than one oral preventive medication
at a stable dose. If the dose and/or type of preventive treatment
changed during OnabotA treatment, only data until the previous
injection cycle were pooled in the analysis. However, patients
could continue OnabotA injections under clinical judgement. If
the patient did not nd benets from the canonical 155 U, the
physician could adopt a “follow the pain strategy,” adding up to
40 additional units to the original dose into eight injection sites
in temporalis, occipitalis, and/or trapezius muscles, as suggested
by other authors (16). e study was approved by the Ethical
Committee of Modena (protocol number 394/CE) and performed
in observation of the latest version of the declaration of Helsinki.
Procedures
During every injection session, the mean number of headache
days over 30days (MNHD), the mean number of abortive medi-
cations taken every day (analgesic consumption-AC) and the
mean value of the visual analog scale for pain (VAS) score were
collected from the headache diaries. HI, AC, and VAS score were
considered as the primary end-points of the study.
Patients’ quality of life was assessed using the HIT-6 score,
which has been specically validated in patients with CM (17);
in particular the Italian version of the HIT-6 was used (Version
1.1 ©2001 QualityMetric, Inc., and GlaxoSmithKline Group of
Companies).
Mental and physical health were analyzed using the Italian
version of the 36-items short form health survey questionnaire
(SF-36) (18). Anxious and depressive symptoms were analyzed
using the Zung self-rating anxiety scale (ZUNG-A) and the Zung
self-rating depression scale (ZUNG-D), respectively (19). HIT-6,
SF-36 mental and physical, ZUNG-A and ZUNG-D scores
were considered as secondary end-points. e abovementioned
questionnaires were lled by patients before every injection and
explored the previous 3months.
Statistical Analysis
All continuous variables were expressed as mean±SD, categori-
cal ones were expressed as proportions and percentages. For all
end-points, a simple linear regression model was built using the
end-point itself as dependent variable and injection cycle number
as the independent one. e slopes of abovementioned models
were analyzed to explore the mean change of every outcome for
a single injection session through time, in order to identify an
average mean change of the explored parameters through time.
Aer that, end-points means at every injections session from
the 18th month onward were compared with baseline using
the one-way analysis of variance followed by Tukey–Kramer
posthoc comparison test, in order to dene if the improvements
previously achieved until the 18th months of treatment (15)
were maintained even on further time-points. e inuence of
a coexistent preventive treatment on the explored outcomes was
explored performing a two-way analysis of variance. Only rst
class preventive treatments in Italian guidelines for headaches
(20) were considered, split for drug classes. Moreover, a Student’s
t-test was performed for every end-point, comparing its mean at
the seventh injection cycle (aer 18months of therapy) with the
mean at the last one to better dene the changes in the explored
parameters between these checkpoints. All results were approxi-
mated at the second decimal gure; linear regression slopes
exploring the mean changes of explored parameters for every
injection session at the third. Statistical analysis was performed
using the STATAIc 13.1 soware.
RESULTS
Demographic Analysis and Drop-Outs
e analyzed sample was composed by 90 patients,
14 men and 76 women, aged between 35 and 65 years
(mean± SD = 45.21 ± 10.12). e most overused drugs were
triptans (71/90–78.89%) followed by NSAIDs (41/90–45.56%),
while only three patients overused combination drugs (3–3.33%).
Oral drugs were taken by the 88% of patients, the 20% used also
intramuscular drugs and the 15% used also rectal formulations.
irty-four patients used a rst class preventive treatment other
than OnabotA: 4 used anti-hypertensive drugs, 15 antidepres-
sants, and 15 antiepileptics (20). No patients took simultaneously
two rst class preventive treatments. Patients who took anti-
hypertensive drugs stopped them before the seventh injection
cycle, due to inecacy (three patients) and one adverse event
(hypotension), so data from these patients were not pooled in
the two-way analysis of variance. Eight patients underwent the
195 U treatment during no more than one injection cycle each.
Eighty-eight out of 90 patients (97.8%) fullled the diagnostic
criteria for CM at the beginning of the study. Aer the rst
year of treatment, patients suering for CM were 37 out of 59
(62.72%), becoming the 66.67% at the second year (14 out of 21
patients) and the 53.85% at the third year (7 out 13 patients). e
proportion of chronic migraineurs at the baseline is signicantly
lower than the ones at the rst, second, and third year. ose
ones were not signicantly dierent (Fisher’s exact test, data not
shown). All 88 chronic migraineurs at the beginning were also
considerable as MOH-suerers. Aer the rst year of therapy
their percentage decreased to the 59.32% (35 out of 59 patients).
At the second year the proportion of MOH-suerers increased at
13 out of 21 (61.9%) and at the third year became of 7 out of 13
patients (53.85%). MOH-suerers proportion at the baseline was
signicantly higher than the ones at future time-points, but no
signicant dierences were found between them (Fisher’s exact
test, data not shown). 14 out of 90 patients (12.6%) reduced of
at least the 50% the number of headache days aer the rst year
of treatment; at the second year the percentage was the 11.11%
(2/18) and at the third the 7.7% (1/13). Of the 90 patients enrolled,
24 changed the dose and/or type of preventive treatment other
than OnabotA due to side eects and, even if they continued
OnabotA injections, further data were not pooled in the analysis.
One patient tried a muscular electric stimulator without consult-
ing physicians and her data from that moment onward were not
pooled in the analysis. Globally, 14 patients stopped OnabotA
injection during the observation (14/90–15.56%): one patient
TABLE 2 | HI, AC, and visual analog scale for pain (VAS) score means at every time-point and relative 95% CI.
Injection number 1 (n=90) 7 (n=27) 8 (n=21) 9 (n=20) 10 (n=18) 11 (n=18) 12 (n=15) 13 (n=13)
Mean number of headache days over
30days
0.98±0.16 0.52±0.34** 0.5±0.27** 0.51±0.3** 0.53±0.3** 0.49±0.31** 0.48±0.3** 0.49±0.29**
VAS 7.66±1.56 3.57±1.35** 3.52±1.97** 3.55±1.79** 3.44±1.69** 3.61±1.61** 3.27±1.67** 3.31±1.25**
AC 1.98±1.69 0.53±0.42** 0.5±0.27** 0.48±0.28** 0.53±0.3** 0.47±0.28** 0.49±0.29** 0.49±0.29*
*P<0.05, **P<0.01, signicance refers to the result of one-way ANOVA followed by Tukey–Kramer posthoc comparison test. Every column is named with the number treatment
cycle after the rst injections. Numbers in brackets indicate patients.
TABLE 1 | Linear regression slopes and relative 95% CI.
End-point Slope [95% CI]
Mean number of headache days over 30days 0.044 [0.051 to 0.037]**
Visual analog scale for pain 0.423 [0.47 to 0.376]**
AC 0.111 [0.14 to 0.082]**
6-items headache impact test 0.726 [0.904 to 0.548]**
SF-36 P 2.106 [1.61 to 2.603]**
SF-36 M 2.205 [1.659 to 2.701]**
ZUNG-A 0.714 [0.954 to 0.473]**
ZUNG-D 0.607 [0.887 to 0.327]**
*P<0.05, **P<0.01.
The signicance refers to the Wald t-statistic test built up on models’ slopes to test the
null hypothesis according with slope itself is not signicantly different from 0.
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Guerzoni et al. Three Years Therapy with OnabotA in Migraine
Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
decided to stop treatment because she was almost pain-free,
three patients were lost at follow-up and 10 patients discontinued
OnabotA due to lack of ecacy. No drop-outs were caused by
OnabotA-related AEs. Globally, only patients who discontinued
OnabotA treatment because of lack of benet and those ones who
were lost at follow-up were considered as drop-outs, giving an
overall number of drop-outs of 13/90 (14.44%).
Linear Regression Models for All
End-Points
All linear regression models performed had a statistically signi-
cantly slope, indicating a signicantly mean change over zero of
the explored outcomes for single injection session. In particular, a
signicantly (P<0.01) mean reduction in all primary end-points
(MNHD, VAS, score and AC) at every injection session was noted.
A general signicantly (P<0.01) reduction was also observed for
the HIT-6, ZUNG-A and ZUNG-D scores. Moreover, a statisti-
cally signicant (P<0.01) increase was seen for the means of
SF-36 scores, both mental and physical. All results are summa-
rized in Table1.
One-Way Analysis of Variance for Primary
and Secondary End-Points, Student’s
t-Test between the Seventh and the Last
Injection Cycle and Two-Way Analysis
of Variance
Mean number of headache days over 30days, CA, and VAS score
means were signicantly lower than baseline at every injection
session from the 18th month of treatment onward, but not always
lower than the previous time-point. e changes observed for
MNHD and VAS scores were followed by similar ones for the
AC, signicantly lower than baseline at all time-points from the
18th month of therapy onward. All those results are summarized
in Ta b le  2. e HIT-6 means at the seventh injection cycle and
subsequent ones resulted always signicantly lower than baseline
(P<0.05) and showed also a continuous, gradual decrease. Also
SF-36 mental and physical scores were signicantly lower than
baseline at every injection session from the 18th months onward.
ZUNG-A and ZUNG-D scores were not signicantly dierent
from baseline even if a gradual improvement was found. Only
ZUNG-A score mean at the 33rd month of treatment was signi-
cantly lower than baseline (P<0.05). In Figure1, we reported
the MNHD, AC, VAS score, HIT-6 score and SF-36 mental and
physical scores means at every injection session with the corre-
sponding 95% condence intervals (CI). Secondary end-points
changes VS baseline are reported in Tab l e 3 . e Student’s t-tests
performed outpointed that the means of all explored parameters
were not signicantly dierent between the seventh injection
cycle and the last one (13th) (Tab l e 4 ). e two-way analysis of
variance performed showed no signicant dierences between
the mean of the explored end-points in the dierent preventive
treatments group for all explored parameters (data not shown).
Adverse Events
All treated patients had only mild side eects and none of them
caused patients’ discontinuation from OnabotA injections. e most
frequent AEs were transitory and localized in the injection sites,
mainly due to the injection procedure rather than OnabotA eects.
ey were: erythema (7/90, 7.7%), injection-site edema (3/90, 3.3%)
and itching (3/90, 3.3%). OnabotA-dependent AEs were: muscles
weakness (3/90, 3.3%), headache (2/90, 2.2%), and transitory pal-
pebral ptosis (1/90, 1.1%). Globally, the 13.3% of patients suered
for an AE. No correlation were seen between AEs and injection
number: all AEs were equally distributed across all injection sessions
(data not shown). All AEs are summarized in Table5.
DISCUSSION
Chronic migraine complicated with MOH is a hard challenge for
clinicians dealing with headaches, because of its high frequency,
its clinical impact, and the enormous treatments failure rate (21).
Poor ecacy and low adherence to prophylaxis treatments are the
most relevant issues (22), and they could aect OnabotA too, as
demonstrated in other conditions rather than CM (23). To assess
OnabotA eectiveness over time, its mean eect through the
injection cycles was analyzed. e linear regression model slopes
outpointed a signicant mean improvement for all outcomes
TABLE 3 | ZUNG-A, ZUNG-D, 6-items headache impact test (HIT-6), and SF-36 Mental and Physical scores at every time-point VS baseline.
Injection number 1 (n=90) 7 (n=27) 8 (n=21) 9 (n=20) 10 (n=18) 11 (n=18) 12 (n=15) 13 (n=13)
HIT-6 65.1±6.24 60.04±7.2* 58.52±8.04** 57.85±7.44** 57.22±7.3** 58.28±8.37* 57.2±7.88** 57.15±5.7*
SF-36P 43.51±18.49 58.58±23.32* 60±22.47* 63.22±21.16** 67.22±16.93** 63.83±21.71** 65.07±16.7** 65.2±14.53*
SF-36M 46.14±21.3 61.55±21.83* 63.9±20.78* 67.25±21.07** 68.39±18.64** 67.4±22.96* 69.12±20.02* 69.13±15.1*
ZUNG-A 42.19±10.42 39.32±8.51 37.19±9.58 36.05±7.05 35.28±8.49 35.61±7.47 33.2±8.06* 34.69±7.41
ZUNG-D 43.02±11.38 41.18±9.53 39.1±9.58 38.45±10.03 37.65±10.83 38±11.26 36.21±11.29 36.23±10.19
*P<0.05, **P<0.01, signicance refers to the result of one-way ANOVA followed by Tukey–Kramer posthoc comparison test. Every column is named with the number of months
after the rst injections. Numbers in brackets indicate patients.
FIGURE 1 | Sub-graphs indicate the means and the relative 95% condence intervals of the explored parameters, despite the ZUNGA and ZUNGD scores, for every
injection session. In particular, the trend of the following outcome has been represented: mean headache days over 30 days 492 (sub-graph A), mean number of
abortive medications taken every day (sub-graph B), visual analog scale for pain score (sub-graph C), 6-items headache impact test score (sub-493 graph D), SF-36
physical score (sub-graph E), and SF-36 mental score (sub-graph F). *mean number of abortive medications taken every day.
TABLE 4 | Student’s t-test for the primary and secondary end-points at the 18th
and the 36th month of treatment.
End-point Mean comparison
Mean number of headache days over
30daysMNHD
0.52±0.34 VS 0.49±0.29
Visual analog scale for pain 3.57±1.35 VS 3.31±1.25
AC 0.53±0.42 VS 0.49±0.29
ZUNG-D 41.18±9.53 VS 36.23±10.19
ZUNG-A 39.32±8.51 VS 34.69±7.41
SF-36M 61.55±21.83 VS 69.13±15.1
SF-36P 58.58±23.32 VS 65.2±14.53
6-items headache impact test 60.04±7.5 VS 57.15±5.7
*P<0.05, **P<0.01.
TABLE 5 | Treatment AEs.
Adverse event Number of patients (%)
Injection-site edema 3/90 (3.33)
Injection-site itching 3/90 (3.33)
Muscles weakness 4/90 (4.44)
Headache 1/90 (1.11)
Neck pain 1/90 (1.11)
Eyelid ptosis 1/90 (1.11)
Total 12/90 (13.33)
5
Guerzoni et al. Three Years Therapy with OnabotA in Migraine
Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
and this seems to indicate a signicant, continuous and stable,
OnabotA action over time. e most remarkable improvements
were observed in the rst year of therapy (Figure1), and the
results are stable over time, as pointed out also by other authors
(2426). e improvements of explored outcomes found out with
the linear regression models were further analyzed to check their
impact on clinical practice, performing the one-way analysis of
variance. Primary end-points were signicantly lower than base-
line at every injection session from the eighteenth month (seventh
cycle) onward, indicating the persistence of OnabotA eects, even
aer years (Tab l e 2). is has been conrmed for shorter periods
of time by other authors (2428), and by the low anti-OnabotA
antibodies production showed in a recent meta-analysis (29).
6
Guerzoni et al. Three Years Therapy with OnabotA in Migraine
Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
In our experience, pain intensity and frequency have a similar
trend: between the rst and the last injection cycle, VAS score had
a reduction rate of 52%, while MNHD about 45%. is reduction
in the MNHD and its trend are substantially reected by the
percentage of chronic migraineurs at every year of therapy: a big-
ger amelioration was seen aer the rst year, with a subsequent
stabilization: this proposes once again the possible existence of
placebo eect, especially during the rst month of treatment
(10). e reduction in AC is more relevant, showing a higher
improvement than in other studies (24, 25, 28, 30). e reduction
in AC indicates that OnabotA could be a useful therapy to reduce
the analgesics overuse, even without a detox therapy (31). is
is corroborated by the fact that MOH-suerers have a similar
trend, decreasing from the 97.8% of the beginning to the 59.32%
aer the rst year. At the second year, a small worsening in their
proportion was registered (61.9%), while at the end the propor-
tion sets on 53.85%. e last three proportion were signicantly
dierent from the baseline, but not between them, conrming
once again the stability of OnabotA eect aer the rst year of
treatment (24, 25). Regarding the headache impact on patients
quality of life, the HIT-6 score means decrease at every time-
point, from the 18th months onward. e persistence of HIT-6
reduction over time has been shown by other authors, even if for
a brief period (24, 28). A stable and long-lasting improvement is
a desirable goal in the management of the third most-disabling
condition worldwide in under 50s (32, 33). Accordingly, physi-
cal and mental health status scores improved through injection
sessions, as stated by the SF-36 physical and mental means scores,
which were signicantly higher at every time-point, compared
with baseline (Tabl e  3 ). Similar to long term experiences in
other therapeutic indications (such as several kinds of cervical
dystonia), a majority of patients comply with repeated treatment
because it provides a good and stable eect over time (34). Notably,
this result was achieved despite the patients we studied had high
values of MNHD, AC, VAS, and HIT-6 scores at baseline, a long
migraine history and a high comorbidity rate (82%). Unlike
previously studied outcomes, ZUNG-A and ZUNG-D scores
means did not change signicantly from baseline, conrming
our previous ndings (15). OnabotA ecacy on anxious and
depressive symptoms, associated or not with chronic pain, is a
matter of debate and a growing amount of literature is dealing on
it, with disagreeing results. Two randomized placebo-controlled
trials revealed positive eects of OnabotA in depressed patients:
Wollmer and colleagues demonstrated that OnabotA injections
in the glabellar region improved the Hamilton depression
rating scale (HDRS) in a cohort of 15 depressed patients (35),
while Finzi and Rosenthal obtained similar results using the
Montgomery–Asberg Depression Rating Scale (MADRS) (36).
Hence, Hexsel and colleagues found a signicant improvement
in Beck depression inventory (BDI) score aer OnabotA injec-
tions in the corrugator muscle of major-depressed patients (37).
However, Aydinlar et al. found no signicant changes in the
21-items depression, anxiety, and stress (DASS-21) score aer
1year of therapy (38), and Maasumi etal. revealed no signicant
changes in the median of patient health questionnaire-9 (PHQ-
9) (39). Despite the question about the OnabotA eects on
depressive symptoms remains open (40), in our observations no
improvements on depressive or anxiety symptoms were observed
using ZUNG-A and ZUNG-D scores. e small sample sizes and
the dierent questionnaires administered limit the reliability of
every comparison. As far as it concerns the OnabotA safety pro-
le, it is still conrmed even aer 3years of therapy. e lack of
drop-outs due to AEs and the majority of them due to the injec-
tion procedure, rather than OnabotA-related events, conrms its
high tolerability (2428, 34). e combination of OnabotA safety
and eectiveness gives reasons to its high and consistent adher-
ence also in the long term, with a discontinuation rate much
lower than other prophylactic drugs, around 50% already aer
only 6months of treatment (41). Neither tolerability nor ecacy
were analyzed comparing 155 U and the 195 U dosages, because
the patients who underwent the “follow the pain” strategy were
only 8 and in isolated cases, strongly limiting the reliability of
any statistical analysis. e co-existence of another preventive
treatment did not aect OnabotA response: from the two-way
analysis of variance no signicantly dierences were found in the
means of the explored parameters between the dierent class A
preventive drugs for migraine (data not shown), even if the small
number of patients in the last injections limits the reliability of
this analysis. is study has some limits: the lack of a control
group makes impossible to quantify the placebo eect. Placebo
response is usually high in migraine and even higher during
OnabotA treatment (4244), but the uncertain data regarding
placebo persistence aer 18months and the stable ameliorations
aer that time-point suggest a pharmacological eect rather than
placebo. A strong reduction in the number of patients was seen
from the 1st to the 13th injection: 24 patients changed preven-
tive treatment other than OnabotA and were excluded from the
computation, one tried a muscular electric stimulator, 14 patients
were considered as drop-outs and 38 are still on treatment.
CONCLUSION
OnabotulinumtoxinA is an eective and safe treatment for CM
complicated with MOH as conrmed by our experience in
the short and long term. OnabotA did not show any incoming
tolerance and its eectiveness was conrmed to be long-lasting,
generating stable improvements in headache symptoms and
patients’ quality of life. ese ndings strongly contribute to
support the benets of long term regular administrations of
OnabotA injections for several years in order to maintain a
consistent migraine relief. A recent Italian survey outpoints that
one-third of clinicians discontinue OnabotA if the benets persist
for at least 6months, oen postponing the injections for more
than 3months (44). Our experience demonstrated that OnabotA
can be administered continuously over several years, according to
the PREEMPT protocol, thanks to its persistent ecacy, its good
AEs-related prole and taking into account a potential worsening
of the symptoms aer its suspension (15).
ETHICS STATEMENT
is study was carried out in accordance with the recommenda-
tions of Provincial Ethical Committee of Modena with written
informed consent from all subjects. All subjects gave written
informed consent in accordance with the Declaration of Helsinki.
7
Guerzoni et al. Three Years Therapy with OnabotA in Migraine
Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
e protocol was approved by the Provincial Ethical Committee
of Modena (protocol number: 334/15).
AUTHOR CONTRIBUTIONS
LAP, SG, MC, LP, AN, and PM draed the manuscript. CB made
statistic calculations and contributed to dra the manuscript. LP
and SG conceived the study. All authors read and approved the
nal manuscript.
ACKNOWLEDGMENTS
Publication fees for this manuscript were supported by Allergan
SpA-Italy.
REFERENCES
1. Natoli JL, Manack A, Dean B, Butler Q, Turkel CC, Stovner L, etal. Global
prevalence of chronic migraine: a systematic review. Cephalalgia (2010)
30:599–609. doi:10.1111/j.1468-2982.2009.01941.x
2. Headache Classication Committee of the International Headache Society
(IHS). e International Classication of Headache Disorders, 3rd edition (beta
version). Cephalalgia (2013) 33:629–808. doi:10.1177/0333102413485658
3. Seng EK, Buse DC, Klepper JE, Mayson SJ, Grinberg AS, Grosberg BM,
et al. Psychological factors associated with chronic migraine and severe
migraine-related disability: an observational study in a Tertiary Headache
Center. Headache (2017) 57:593–604. doi:10.1111/head.13021
4. Stokes M, Becker WJ, Lipton RB, Sullivan SD, Wilcox TK, Wells L, etal. Cost
of health care among patients with chronic and episodic migraine in Canada
and the USA: results from the International Burden of Migraine Study (IBMS).
Headache (2017) 51:1058–77. doi:10.1111/j.1526-4610.2011.01945.x
5. Tajti J, Majláth Z, Szok D, Csáti A, Vécsei L. Drug safety in acute migraine
treatment. Expert Opin Drug Saf (2015) 14:891–909. doi:10.1517/14740338.
2015.1026325
6. Negro A, Martelletti P. Chronic migraine plus medication overuse head-
ache: two entities or not? J Headache Pain (2011) 12:593–601. doi:10.1007/
s10194-011-0388-3
7. Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to
oral migraine-preventive medications among patients with chronic migraine.
Cephalalgia (2015) 35:478–88. doi:10.1177/0333102414547138
8. Hepp Z, Bloudek LM, Varon SF. Systematic review of migraine prophy-
laxis adherence and persistence. J Manag Care Pharm (2014) 20:22–33.
doi:10.18553/jmcp.2014.20.1.22
9. Rossi P, Jensen R, Nappi G, Allena M; e COMOESTAS Consortium.
A narrative review on the management of medication overuse headache: the
steep road from experience to evidence. J Headache Pain (2009) 10:407–17.
doi:10.1007/s10194-009-0159-6
10. Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silbertstein SD, Lipton RB,
etal. OnabotulinumtoxinA for treatment of chronic migraine: results from the
double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial.
Cephalalgia (2010) 30:793–803. doi:10.1177/0333102410364676
11. Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB,
etal. OnabotulinumtoxinA for treatment of chronic migraine: results from
the double-blind, randomized, placebo-controlled phase of the PREEMPT 2
trial. Cephalalgia (2010) 30:804–14. doi:10.1177/0333102410364677
12. Lipton RB, Rosen NL, Ailani J, DeGryse RE, Gillard PJ, Varon SF.
OnabotulinumtoxinA improves quality of life and reduces impact of chronic
migraine over one year of treatment: pooled results from the PREEMPT
randomized clinical trial program. Cephalalgia (2016) 36:899–908.
doi:10.1177/0333102416652092
13. Mathew NT, Jari SFA. A double-blind comparison of onabotulinum-
toxinA (BOTOX®) and topiramate (TOPAMAX®) for the prophylactic
treatment of chronic migraine: a pilot study. Headache (2009) 49:1466–78.
doi:10.1111/j.1526-4610.2009.01566.x
14. Gooriah R, Fayyaz A. OnabotulinumtoxinA for chronic migraine: a critical
appraisal. er Clin Risk Manag (2015) 11:1003–13. doi:10.214/TCRM.S76964
15. Guerzoni S, Pellesi L, Baraldi C, Pini LA. Increased ecacy of regularly
repeated cycles with OnabotulinumtoxinA beyond the rst year of treatment.
J Headache Pain (2015) 17:48. doi:10.1186/s10194-016-0634-9
16. Blumenfeld A, Silberstein SD, Dodick DW, Aurora SK, Turkel CC, Binder WJ.
Method of injection of onabotulinumtoxinA for chronic migraine: a safe,
well-tolerated, and eective treatment paradigm based on the PREEMPT clinical
program. Headache (2010) 50:1406–18. doi:10.1111/j.1526-4610.2010.01766.x
17. Rendas-Baum R, Yang M, Varon SF, Bloudek LM, DeGryse RE, Kosinski M.
Validation of the Headache Impact Test (HIT-6) in patients with chronic
migraine. Health Qual Life Outcomes (2014) 12:117. doi:10.1186/s12955-
014-0117-0
18. Apolone G, Mosconi P. e Italian SF-36 health survey: translation,
validation and norming. J Clin Epidemiol (1998) 51:1025–36. doi:10.1016/
S0895-4356(98)00094-8
19. Zung WWK. From art to science. e diagnosis and treatment of
depression. Arch Gen Psychiatry (1973) 29:328–37. doi:10.1001/
archpsyc.1973.04200030026004
20. Sarchielli P, Granella F, Prudenzano MP, Pini LA, Guidetti V, Bono G, etal.
Italian guidelines for primary headaches: 2012 revised version. J Headache
Pain (2012) 13:S31–70. doi:10.1007/s10194-012-0437-6
21. Lipton RB. Tracing transformation: chronic migraine classication,
progression, and epidemiology. Neurology (2009) 72:S3–7. doi:10.1212/
WNL.0b013e3181974b19
22. D’Amico D, Tepper SJ. Prophylaxis of migraine: general principles and
patients acceptance. Neuropsychiatr Dis Treat (2008) 4:1155–67. doi:10.2147/
NDT.S3497
23. Dressler D, Wohlfahrt K, Meyer-Rogge E, Wiest L, Bigalke H. Antibody-
induced failure of botulinum toxin a therapy in cosmetic indications. Dermatol
Surg (2010) 36:2182–7. doi:10.1111/j.1524-4725.2010.01710.x
24. Negro A, Curto M, Lionetto L, Crialesi D, Martelletti P. OnabotulinumtoxinA
155 U in medication overuse headache: a two years prospective study.
Springerplus (2015) 30:826. doi:10.1186/s40064-015-1636-9
25. Negro A, Curto M, Lionetto L, Martelletti P. A two years open-label
prospective study of OnabotulinumtoxinA 195 U in medication overuse
headache: a real-world experience. J Headache Pain (2015) 17:1. doi:10.1186/
s10194-016-0591-3
26. Vikelis M, Argyriou AA, Dermitzakis EV, Spingos KC, Mitsikostas DD.
Onabotulinumtoxin-A treatment in Greek patients with chronic migraine.
J Headache Pain (2016) 17:84. doi:10.1186/s10194-016-0676-z
27. Aicua-Rapun I, Martínez-Velasco E, Rojo A, Hernando A, Ruiz H, Carreres A, etal.
Real-life data in 115 chronic migraine patients treated with Onabotulinumtoxin
A during more than one year. J Headache Pain (2016) 17:112. doi:10.1186/
s10194-016-0702-1
28. Khalil M, Zafar HW, Quarshie V, Ahmed F. Prospective analysis of the use
of OnabotulinumtoxinA (BOTOX) in the treatment of chronic migraine;
real-life data in 254 patients from Hull, UK. J Headache Pain (2014) 15:54.
doi:10.1186/1129-2377-15-54
29. Naumann M, Carruthers A, Carruthers J, Aurora SK, Zafonte R, Abu-
Shakra S, et al. Meta-analysis of neutralizing antibody conversion with
onabotulinumtoxinA (BOTOX) across multiple indications. Mov Disord
(2010) 13:2211–8. doi:10.1002/mds.23254
30. Pedraza MI, de la Cruz C, Ruiz M, López-Mesonero L, Martínez E,
de Lera M, etal. OnabotulinumtoxinA for chronic migraine: experience in
52 patients treated with the PREEMPT paradigm. Springerplus (2015) 4:176.
doi:10.1186/s40064-015-0957-z
31. Butera C, Colombo B, Bianchi F, Cursi M, Messina R, Amadio S, et al.
Refractory chronic migraine: is drug withdrawal necessary before starting
a therapy with onabotulinum toxin type A? Neurol Sci (2016) 37:1701.
doi:10.1007/s10072-016-2662-2
32. Steiner TJ, Stovner LJ, Vos T. GBD 2015: migraine is the third cause of disability
in under 50s. J Headache Pain (2016) 17:104. doi:10.1186/s10194-016-0699-5
33. Autret A, Roux S, Rimbaux-Lepage S, Valade D, Debiais S; West Migraine
Study Group. Psychopathology and quality of life burden in chronic daily
headache: inuence of migraine symptoms. J Headache Pain (2010) 11:247–53.
doi:10.1007/s10194-010-0208-1
8
Guerzoni et al. Three Years Therapy with OnabotA in Migraine
Frontiers in Neurology | www.frontiersin.org November 2017 | Volume 8 | Article 586
34. Colosimo C, Tiple D, Berardelli A. Ecacy and safety of long-term botulinum
toxin treatment in craniocervical dystonia: a systematic review. Neurotox Res
(2012) 22:265–73. doi:10.1007/s12640-012-9314-y
35. Wollmer MA, De Boer C, Kalak N, Beck J, Götz T, Schmidt T, etal. Facing
depression with botulinum toxin: a randomized controlled trial. J Psychiatr
Res (2012) 46:574–81. doi:10.1016/j.jpsychires.2012.01.027
36. Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxinA:
a randomized, double-blind, placebo-controlled trial. J Psychiatr Res (2014)
52:1–6. doi:10.1016/j.jpsychires.2013.11.006
37. Hexsel D, Brum C, Siega C, Schilling-Souza J, Dal’Forno T, Heckmann M,
etal. Evaluation of self-esteem and depression symptoms in depressed and
non-depressed subjects treated with onabotulinumtoxinA for glabellar lines.
Dermatol Surg (2013) 39:1088–96. doi:10.1111/dsu.12175
38. Aydinlar EI, Dikmen PY, Kosak S, Kocaman AS. OnabotulinumtoxinA
eectiveness on chronic migraine, negative emotional states and sleep qual-
ity: a single-center prospective cohort study. J Headache Pain (2017) 18:23.
doi:10.1186/s10194-017-0723-4
39. Maasumi K, ompson NR, Kriegler JR, Tepper SJ. Eect of onabotuli-
numtoxinA injection on depression in chronic migraine. Headache (2016)
55:1218–24. doi:10.1111/head.12657
40. Kruger TH, Wollmer MA. Depression – an emerging indication for
botulinumtoxin treatment. Tox i con (2015) 107(Pt A):154–7. doi:10.1016/
j.toxicon.2015.09.035
41. Hepp Z, Dodick DW, Varonl SF, C hia J, Matthew N, Gillardl P, etal. Persistence
and switching patterns of oral migraine prophylactic medications among
patients with chronic migraine: a retrospective claims analysis. Cephalalgia
(2017) 37:470–85. doi:10.1177/0333102416678382
42. Speciali JG, Peres M, Bigal ME. Migraine treatment and the placebo eect.
Expert Rev Neurother (2010) 10:413–9. doi:10.1586/ern.10.8
43. Lee IS, Lee B, Park HJ, Olausson H, Enck P, Chae Y. A new animal model
of placebo analgesia: involvement of the dopaminergic system in reward
learning. Sci Rep (2015) 5:17140. doi:10.1038/srep17140
44. Tassorelli C, Aguggia M, De Tommaso M, Geppetti P, Grazzi L, Pini LA, etal.
OnabotulinumtoxinA for the management of chronic migraine in current
clinical practice: results of a survey of sixty-three Italian headache centers.
J Headache Pain (2017) 18:66. doi:10.1186/s10194-017-0773-7
Conict of Interest Statement: LP and SG received grants and travel honoraria
from Allergan. PM received honoraria, travel bureau, research grant, and advisory
board from ACRAF, Allergan, Amgen, Electrocore, Elytrapharma. AN received
honoraria, travel bureau, research grant, advisory board from Allergan. e
authors declare that the research was conducted in the absence of any commercial
or nancial relationships that could be construed as a potential conict of interest.
e reviewer CD declared a shared aliation, with no collaboration, with several
of the authors, PM and AN, to the handling Editor.
Copyright © 2017 Guerzoni, Pellesi, Baraldi, Cainazzo, Negro, Martelletti and Pini.
is is an open-access article distributed under the terms of the Creative Commons
Attribution License (CC BY). e use, distribution or reproduction in other forums
is permitted, provided the original author(s) or licensor are credited and that the
original publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction is permitted which does not comply
with these terms.
... In selected cases, we increased the dosage of OBT-A up to a maximum of 195 I.U. [19]. ...
... Categorical and dichotomous variables were presented as numbers and percentages and compared with the chi-square test. We considered a "responder" to be any subject with a reduction in the number of seizures or a reduction in the MIDAS score of at least 50% [19,20]. ...
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Chronic migraine is a burdensome disease presenting with episodic pain and several symptoms that may persist even among headache attacks. Multisensory integration is modified in migraine, as assessed by the level of the perception of sound-induced flash illusions, a simple paradigm reflecting changes in cortical excitability which reveals to be altered in migraineurs. OnabotulinumtoxinA is an effective preventive therapy for chronic migraineurs, reducing peripheral and central sensitization, and may influence cortical excitability. Patients affected by chronic migraine who started onabotulinumtoxinA preventive therapy were included. Clinical effects (headache diaries and migraine related questionnaires) were assessed at the beginning of the therapy and after 12 weeks. Contextually, patients underwent the evaluation of multisensory perception by means of the sound-induced flash illusions. OnabotulinumtoxinA showed effectiveness both in migraine prevention and in reducing headache burden. Even one session of therapy was able to restore, at least partially, multisensory processing, as shown by patients’ susceptibility to the sound-induced flash illusion. OnabotulinumtoxinA could influence migraineurs cortical excitability concurrently to the beneficial effects in headache prevention.
... Исследование порогов ТЧ и БЧ у пациентов с ХМ проводилось до начала лечения и через 3-4 недели после проведенной терапии. Инъекции abobotulinumtoxinA (Dysport) в заинтересованные мышцы лица и шеи выполнялись в точки согласно международной стандартной схеме, предложенной А. Блюменфельдом и соавторами [10]. Для ботулинотерапии использовалось лекарственное средство диспорт в дозе 300 ЕД впервые, разведение физиологическим раствором 1,5 мл на 300 ЕД препарата. ...
Article
Цель. Изучить пороги тактильной и болевой чувствительности (ТЧ и БЧ) по данным эстезиометрии у пациентов с хронической мигренью (ХМ) до и после лечения инъекциями ботулинического токсина типа А (БТА).Материалы и методы. В исследование вошли 67 пациентов с ХМ, из них 52 женщины и 15 мужчин. Соотношение женщин и мужчин в группе было 3,16 : 1. Средний возраст – 38 [31; 47] лет. Контрольную группу составили 30 здоровых лиц, соотношение женщин и мужчин составило 1,14 : 1, по возрасту группы мужчин и женщин были идентичны исследуемым (р>0,05).Определение порогов ТЧ и БЧ выполнялось на приборе «ЭстезиметрЭ-01». Был разработан протокол для исследования порогов ТЧ и БЧ для пациентов с ХМ. Исследование порогов у пациентов с ХМ проводилось до начала лечения и через 3–4 недели после проведенной терапии. Инъекции abobotulinumtoxinA (Dysport) в заинтересованные мышцы лица и шеи выполнялись в точки согласно международной стандартной схеме, предложенной А. Блюменфельдом и соавторами. Всего 23 пациента получили лечение БТА, из них 18 женщин и 5 мужчин. Изменения схемы медикаментозной терапии в оцениваемый период не проводилось.Результаты. В результате исследования было установлено статистически значимоеснижение порогов ТЧ и БЧ у пациентов женского и мужского пола с ХМ, по сравнению с группой здоровых лиц, в области лба, щек, височной области, в проекции височно-нижнечелюстных суставов и жевательных мышц, а также порогов БЧ в области трапециевидных мышц. При оценке динамики показателей после лечения локальными инъекциями БТА в группе женщин наблюдалась тенденция к повышению порогов ТЧ и БЧ, но при этом значения не достигали условной нормы по сравнению с группой здоровых лиц (р<0,05).Полученные новые научные данные соответствуют современной концепции патофизиологии ХМ. Считается, что ключевым механизмом в разворачивании приступа мигрени является активация и сенситизация тригемино-васкулярной системы.Заключение. Полученные данные указывают на повышенную активацию и сенситизацию тригемино-васкулярной системы при ХМ. Инъекции БТА уменьшали пороги ТЧ и БЧ при ХМ, что свидетельствует о воздействии БТА на нейрональную гипервозбудимость при ХМ. Purpose. To study the thresholds of tactile and pain sensitivity (TS and PS) according to esthesiometry in patients with chronic migraine (CM) before and after treatment with injections of botulinum toxin type A (BTA).Materials and methods. The study included 67 patients with CM, including 52 women and 15 men. The female to male ratio in the group was 3.16 : 1. The mean age was 38 [31; 47] years. The control group consisted of 30 healthy individuals, the ratio of women and men was 1.14 : 1, the groups of men and women were identical in age to the studied ones (p>0.05).Determination of TS and PS thresholds was carried out on the device "EstezimetrE-01". A protocol for the investigation of TS and PS thresholds has been developed for the patients with CM. The study of thresholds in patients with CM was carried out before the start of treatment and 3–4 weeks after the therapy. Injections of abobotulinumtoxinA (Dysport) into the affected muscles of the face and neck were performed at points according to the international standard scheme proposed by A. Blumenfeld et al. A total of 23 patients received BTA treatment, of which 18 were women and 5 were men. There were no changes in the drug therapy regimen during the period under review.Results. As a result of the study, a statistically significant decrease in TS and PS thresholds was found in female and male patients with CM compared with a group of healthy individuals in the forehead, cheeks, temporal region, in the projection of the temporomandibular joints and masticatory muscles, as well as PS thresholds in areas of the trapezius muscles. There was a tendency to increase the thresholds for TS and PS in the assessment of the dynamics of indicators after treatment with local injections of BTA in the group of women, but the values did not reach the conditional norm compared to the group of healthy individuals (p<0.05).Conclusion. The obtained new scientific data correspond to the modern concept of the pathophysiology of CM. It is believed that the key mechanism in the development of a migraine attack is the activation and sensitization of the trigeminovascular system.
... The purposive sample was influenced by the availability of participants, which could potentially influence the results by including a sub-group of patients, who were poor responders to, or unhappy with, previous treatment strategies. However, there is some evidence to suggest that the more time after chronicity of migraine that passes, the less effective OBT-A might be [36]. Most patients in our study group had suffered with chronic migraine for many years prior to OBT-A treatment. ...
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IntroductionOnabotulinumtoxinA (OBT-A) is one of the most studied prophylactic treatments for chronic migraine. Large clinical trials, and now real-world studies, continue to provide evidence to support the use of OBT-A as an effective treatment to manage chronic migraine. The objective of this study was to explore patient experience and perception of prophylactic treatment with OBT-A for chronic migraine.Methods Data were collected using semi-structured interviews using open-ended questions to uncover rich descriptive data on patient experiences. Interviews were transcribed and analysed using NVivo data analysis software to code and identify themes across the dataset. Three patient groups were included in the analysis: (1) patients who were receiving continued OBT-A treatment; (2) patients who discontinued OBT-A treatment; (3) patients who were recommended for OBT-A treatment but did not proceed.ResultsFor patients who received at least one OBT-A treatment, four main themes emerged, which described patients’ expectations, experiences, and feelings towards their treatment decisions. Two main themes emerged that were common to patients, who had discontinued their treatment and those, who were recommended for OBT-A treatment but did not proceed, which were identified as potential barriers to initiate or continue prophylactic treatment with OBT-A.Conclusion Understanding patients’ perspective is an important part of clinical practice and may impact on decision-making. Qualitative data can provide a more holistic view of patient care and treatment insights that may not be evaluated during a clinical trial. This study revealed potential barriers to treatment that can inform future policy and practice.
... This variable is usually among the least studied in trials before drugs commercialization and real-world data is also scarce. Some oral prophylactics may keep patients into a low frequency episodic migraine even after interrupted [22], whereas other drugs such as onabotA might need to be periodically administered to keep its effect [23]. Regarding mABs, data is scarce [24] and further research is needed to clarify this. ...
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Background We aim to describe and compare patients and general practitioners’ opinions about the different variables related to acute and preventive treatment for migraine. Patients and methods An observational descriptive study was performed. Patients with episodic migraine and general practitioners, from our healthcare area, were invited to answer a survey about the different variables related to migraine treatment. They were asked for their opinions on the different variables, and to consider the desired efficacy in percentage terms and the desired action times of treatment. Results Fifty-five patients and fifty-five general practitioners were selected. Effectiveness was considered the most important variable for symptomatic and preventive treatment. Cost was considered the least important variable. Patients desired percentage of efficacy was 84.0% (±16.7%) for symptomatic treatment and 79.9% (±17.1%) for preventive treatment. General practitioners desired percentage of efficacy was 75.0% (±14.0) for symptomatic treatment and 70.4% (±14.3) for preventive treatment. For symptomatic treatment the desired action time for pain cessation was selected as 27.5 min (±13.8) for patients and 24.0 min (±18.3) for GPs. For preventive treatment the desired action time for effect was 7.1 days (±4.5) for patients and 13.9 days (±8.9) for general practitioners. Conclusion The most important endpoints were, for acute: effectiveness, a short action time and a persistent effect. For prophylactic: effectiveness, sustained effect and tolerability. Both patients and general practitioners agreed on the most and least preferred endpoints. Desired percentage of efficacy was above 75% for both symptomatic and preventive treatment; and the desired action time was below 30 min for acute treatment and 2 weeks for preventive treatment.
... This may be explained by the method of administration. Botulinum toxin is administered to at least 31 injection sites across seven head and neck muscles (Tassorelli et al., 2018), while CGRP is more convenient and easier to operate using subcutaneous or intravenous infusion. ...
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Background: The previously approved botulinum toxin and nowadays promising calcitonin gene-related peptide (CGRP) monoclonal antibody have shown efficacy for preventing chronic migraine (CM). However, there is no direct evidence for their relative effectiveness and safety. In this study, we conducted an indirect treatment comparison to compare the efficacy and safety of CGRP monoclonal antibody with botulinum toxin for the preventive treatment of chronic migraine. Methods: Up to August 31, 2020, we systematically searched PubMed, Embase, and Cochrane Library Central Register of Controlled Trials (Central). Weighted mean difference (WMD) and relative risk (RR) were used to evaluate clinical outcomes. Indirect treatment comparison (ITC) software was used to conduct indirect treatment comparison. Results: Ten studies were pooled with 6,325 patients in our meta-analysis. Both botulinum toxin and CGRP monoclonal antibody demonstrated favorable efficacy in the change of migraine days, headache days, HIT-6 score, and 50% migraine responder rate compared with placebo. In indirect treatment comparison, CGRP monoclonal antibody was superior to botulinum toxin in the frequency of acute analgesics intake (WMD = −1.31, 95% CI: −3.394 to 0.774, p = 0.02113), the rate of treatment-related adverse events (AEs) (RR = 0.664, 95% CI: 0.469 to 0.939, p = 0.04047), and the rate of treatment-related serious adverse events (RR = 0.505, 95% CI: 0.005 to 46.98, p < 0.001). Conclusion: For chronic migraine patients, CGRP monoclonal antibody was slightly better than botulinum toxin in terms of efficacy and safety. In the future, head-to-head trials would be better to evaluate the efficacy and safety between different medications in the prevention of chronic migraine.
Article
Introduction: : Migraine occupies the first position regarding to the disability caused in female working population (15-49 years). Research in the field of prophylaxis of this pathology has made enormous strides in recent years. Areas covered: In this narrative review we retrace the most important scientific evidence regarding recently approved and emerging drug for prophylactic treatment of migraine. The purpose of this article is in fact to evaluate currently approved or emerging pharmacological agents for migraine prophylaxis. This review is based on literature published in peer review journal obtained through PubMed, Cochrane library, Clinicaltrials.gov and US FDA. Expert opinion: : Monoclonal antibodies (mAbs) that target the calcitonin gene-related peptide signalling pathway (CGRP) have marked an innovation in prophylactic migraine therapy. The combination of Onabotulinumtoxin-A (OBTA) and mAbs appears to be an effective, but costly, therapeutic option for resistant cases. New classes of molecules like gepants and ditans seem to give exceptional results. In addition, new prophylactic drugs are emerging with several targets: the pituitary adenylate cyclase-activating polypeptide (PACAP), ion channels, several receptors coupled to G proteins, orexin, and glutamate. All these therapies will implement and improve migraine management, as well as personalized medicine for each patient.
Article
Цель. Проанализировать результаты лечения пациентов с хронической мигренью (ХМ) препаратом ботулинического токсина типа А (БТА).Материалы и методы. С 2018 г. в Беларуси начата работа по лечению пациентов с ХМ путем выполнения локальных инъекций препаратом БТА в область головы и шеи по международной стандартной схеме, предложенной А. Блюменфельдом и соавторами. В настоящее время инъекции abobotulinumtoxin A (диспорт) получили 18 пациентов с ХМ, из них 15 женщин и 3 мужчин, повторные инъекции были выполнены у 8 пациентов. Медиана возраста пациентов с ХМ и интерквартильный интервал составили 37 [31; 46] лет. Пациенты самостоятельно вели дневник головной боли, заполняли опросник индекса HIT-6 (Headache Impact Test) влияния головной боли на повседневную активность, время нетрудоспособности, связанной с головной болью (индекс HALT – Headache-attributed lost time), проводилась оценка интенсивности головной боли по визуально-аналоговой шкале (ВАШ) до инъекции и через 4 недели после введения БТА.Результаты. В результате терапии инъекциями БТА пациентов с ХМ было получено достоверное снижение частоты и интенсивности головной боли по ВАШ согласно дневникам головной боли в течение месяца, увеличение работоспособности и улучшение качества жизни пациентов по шкале HIT-6 и индексу HALT.Заключение. Полученные данные свидетельствуют об эффективности ботулинотерапии для лечения ХМ, позволяют расширить показания для назначения БТА и свидетельствуют о необходимости проведения дальнейших исследований. Для лечения ХМ БТА может использоваться при неэффективности ранее проведенных курсов лечения или применяться в качестве препарата первой линии при наличии противопоказаний к приему таблетированных превентивных препаратов, а также совместно с этими лекарственными средствами. Purpose. To analyze the results of treatment of patients with chronic migraine (СM) with botulinum toxin type A (BTA).Materials and methods. The work on the treatment of patients with CM by performing local injections with BTA in the head and neck area, according to the international standard scheme proposed by A. Blumenfeld et al., began in Belarus in 2018. Currently, 18 patients with CM received injections of abobotulinumtoxin A (dysport), including 15 women and 3 men, repeated injections were performed in 8 patients. The average age of patients with HM and the interquartile range was 37 [31; 46] years. The patients independently kept the headache diary, filled out the questionnaire of the HIT-6 index (Headache Impact Test) of the effect of headache on daily activity, time of disability associated with headache (HALT index – Headache-attributed lost time); the intensity of headache was assessed visually – analogue scale (VAS) before injection and 4 weeks after administration of BTA.Results. As a result of the therapy with BTA injections in patients with CM, there was observed a significant decrease of the frequency and intensity of headaches, according to the VAS and headache diaries for a month, the increase of work capacity and improvement of the quality of life of patients, according to the HIT-6 scale and the HALT index.Conclusion. The obtained data indicate the effectiveness of botulinum therapy for the treatment of CM, let to expand the indications for prescribing BTA, and indicate the need for further research. Injections of BTA can be used in case of ineffectiveness of previous courses of treatment or used as a first-line drug in the presence of contraindications to taking preventive tablet drugs, as well as in conjunction with these drugs for the treatment of CM.
Article
Monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or on its receptor are new therapeutic biologics to prevent chronic migraine (CM). Four mAbs acting on the CGRP or on its receptor are new therapeutic biologics to prevent CM. The aim of current network meta-analysis (NMA) was to compare the efficacy and acceptability of CGRP mAbs with onabotulinumtoxinA or topiramate for CM. We included randomized controlled trials (RCTs) examining CGRP mAbs and onabotulinumtoxinA or topiramate in patients with CM. All network meta-analytic procedures were conducted using the frequentist model. The primary outcomes were changes in the monthly migraine days and the 50% response rate. The safety was evaluated with acceptability (i.e., drop-out rate) and rate of any adverse event. This NMA of thirteen RCTs, which, in total, consisted of 5634 participants, demonstrated that a single 300 mg of eptinezumab (mean difference = − 2.60 days, 95% confidence intervals (95% CIs) = − 4.43 to − 0.77 compared with placebo) demonstrated the best improvement in monthly migraine days among all interventions. In addition, 675 mg fremanezumab in the first month followed by 225 mg in the second and third months (odds ratio (OR) = 2.96, 95% CIs = 2.20 to 3.97 compared to placebo) was associated with the best response rate among all the interventions. Monthly 140 mg erenumab (MD = − 2.50 days, 95% CIs = − 3.83 to − 1.17 compared with placebo) was the best choice for reducing the number of acute migraine-specific medication use days. The safety analysis revealed that loading dose of 240 mg galcanezumab and monthly 240 mg (OR = 0.43, 95% CIs = 0.22 to 0.84) was associated with the lowest drop-out rate; loading dose fremanezumab 675 mg and monthly 675 mg (OR = 1.44, 95% CIs = 1.10 to 1.89), loading dose of 240 mg galcanezumab and monthly 120 mg (OR = 1.37, 95% CIs = 1.02 to 1.84), and single dose of fremanezumab 675 mg (OR = 1.35, 95% CIs = 1.00 to 1.83) were associated with significantly higher rates of AEs than the placebo/control groups. Our NMA indicated that all four CGRP mAbs demonstrated excellent safety, acceptability, and efficacy profiles compared to the traditional prophylaxis for CM. However, because there are several limitations, the findings of the current NMA should be taken into consideration with caution.
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Background: Relatively little is known about the stability of a diagnosis of episodic migraine (EM) or chronic migraine (CM) over time. This study examines natural fluctuations in self-reported headache frequency as well as the stability and variation in migraine type among individuals meeting criteria for EM and CM at baseline. Methods: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal survey of US adults with EM and CM identified by a web-questionnaire. A validated questionnaire was used to classify respondents with EM (<15 headache days/month) or CM (≥15 headache days/month) every three months for a total of five assessments. We described longitudinal persistence of baseline EM and CM classifications. In addition, we modelled longitudinal variation in headache day frequency per month using negative binomial repeated measures regression models (NBRMR). Results: Among the 5464 respondents with EM at baseline providing four or five waves of data, 5048 (92.4%) had EM in all waves and 416 (7.6%) had CM in at least one wave. Among 526 respondents with CM at baseline providing four or five waves of data, 140 (26.6%) had CM in every wave and 386 (73.4%) had EM for at least one wave. Individual plots revealed striking within-person variations in headache days per month. The NBRMR model revealed that the rate of headache days increased across waves of observation 19% more per wave for CM compared to EM (rate ratio [RR], 1.19; 95% CI, 1.13-1.26). After adjustment for covariates, the relative difference changed to a 26% increase per wave (RR, 1.26; 95% CI, 1.2-1.33). Conclusions: Follow-up at three-month intervals reveals a high level of short-term variability in headache days per month. As a consequence, many individuals cross the CM diagnostic boundary of ≥15 headache days per month.Nearly three quarters of persons with CM at baseline drop below this diagnostic boundary at least once over the course of a year. These findings are of interest in the consideration of headache classification and diagnosis, the design and interpretation of epidemiologic and clinical studies, and clinical management.
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Piero Barbanti,1 Patrizia Ferroni2 1Headache and Pain Unit, Department of Neurological, Motor and Sensorial Sciences, 2Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, IRCCS San Raffaele Pisana, Rome, Italy Abstract: Discovered by serendipity, onabotulinum toxin A (BoNT-A) is the only US Food and Drug Administration-approved treatment for the prevention of chronic migraine (CM), one of the most disabling and burdensome human conditions. Its efficacy, safety and tolerability, proved by the largest and longest migraine therapeutic trial (the Phase III Research Evaluating Migraine Prophylaxis Therapy program [PREEMPT]), have been replicated by various real-life studies also in the presence of medication overuse. The benefit of BoNT-A prophylaxis is likely due to its ability to counteract peripheral and central nociceptive sensitization through reversible chemical denervation of pericranial sensitive afferents. Its efficacy increases considerably over time during long-term treatments, significantly varying among patients. The present review focuses on the state-of-the art of current knowledge on putative instrumental, biochemical and clinical predictors of BoNT-A responsiveness, outlining the need for a thorough characterization of the full phenotypic migraine picture when trying to predict good responders. Available evidence suggests that disentangling the BoNT-A responsiveness puzzle requires 1) a reappraisal of easy-obtainable clinical details (eg, site and quality of pain, presence of cranial autonomic symptoms), 2) a proper stratification of patients with CM according to their headache frequency, 3) the evaluation of potential synergistic effects of concomitant prophylaxis/treatment and 4) a detailed assessment of modifiable risk factors evolution during treatment. Keywords: chronic migraine, onabotulinum toxin A, prophylaxis, treatment responder, patient selection, disability
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Background Migraine is a debilitating neurological disorder that affects 14.1% of the US and 14.7% of the European populations. Chronic migraine (CM) is broadly defined as headache occurring on ≥15 days per month for ≥3 months, and has an estimated worldwide prevalence of 1.4% to 2.2%. OnabotulinumtoxinA is currently approved for the treatment of CM in most European countries, and is the only preventative treatment approved for adults with CM, based on results from the PREEMPT clinical trial programme. The ongoing prospective, observational REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilisation, and Patient-reported OutcomeS observed in practice (REPOSE) Study aims to describe real-world healthcare resource utilisation and patient-reported outcomes over a 2-year period in Germany, Italy, Norway, Russia, Spain, Sweden, and the United Kingdom, among patients with CM prescribed onabotulinumtoxinA. Methods Herein, methodology and baseline characteristics of patients who participated for ≥6 months in REPOSE are reported. No outcomes data are presented, although the methods for collecting these data are detailed. In REPOSE, onabotulinumtoxinA is administered at baseline and each follow-up visit (approximately every 3 months) during the 24-month treatment period, according to the treating physician’s best clinical judgment and standard of care, guided by the terms of the marketing authorisation described in the Summary of Product Characteristics. Outcome assessments include Migraine-Specific Quality of Life Questionnaire (MSQ), EuroQol Group Questionnaire (EQ-5D), headache-day frequency, treatment satisfaction, headache-related healthcare resource utilisation (ie, healthcare professional visits, hospital admissions, medication use), onabotulinumtoxinA utilisation (ie, dose, sites), and safety/tolerability. Results As of the interim assessment date for this analysis, the study has enrolled 644 patients from 78 sites throughout Europe, and baseline data are available for 336 patients from 61 sites who participated in the study for ≥6 months. Baseline measures indicate substantial disease burden and healthcare resource utilisation. Conclusions Final results from the REPOSE Study will provide the largest real-world, long-term analysis of the clinical use of onabotulinumtoxinA for the treatment of CM and will add important information to existing real-world findings. Future analyses will assess the long-term safety and efficacy of onabotulinumtoxinA in this population.
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Background Chronic migraine is a complex clinical condition often undertreated. Onabotulinumtoxin A (OBT-A) was approved in Italy in 2013 for symptom relief in patients with chronic migraine who have failed, or do not tolerate, oral prophylactic treatments. However, the impact of OBT-A in clinical practice remains to be defined. Methods To investigate the current management of chronic migraine with OBT-A in clinical practice, a web-based survey was conducted among clinicians working in third-level headache centers across Italy. A 26-item questionnaire was designed and developed by a group of 10 Italian headache specialists to address the following issues: treatment paradigm and OBT-A injection intervals, frequency of treatment and retreatment, definition of responders/non-responders, satisfaction with treatment potential impact of early treatment with OBT-A. Ninety-six headache centers were selected and contacted via e-mail. The online survey was anonymous and carried out using a secure website. Results Overall, 64 of the 96 centers (66.7%) completed the questionnaire. Most centers (98.4%) had been using OBT-A for >1 year. OBT-A was administered according to the PREEMPT paradigm in most centers (88.9%). While during the first year of prophylaxis with OBT-A most clinicians (93.6%) repeated OBT-A treatment every 3 months, as recommended, in the following years interval duration was variable. Response to OBT-A was defined as a ≥ 50% reduction in the headache days by 58.7% of the clinicians, and as a ≥ 30% reduction by 25.4% of them. Almost 60% of the clinicians considered OBT-A as a long-lasting therapy, while for one-third of them treatment could be discontinued in patients showing a benefit for ≥6 months. According to 80% of the clinicians, early administration of OBT-A after the onset of chronic migraine was associated with better outcomes, and 47.6% felt that OBT-A should be recommended as a first-line option. Conclusions This survey indicates that in third-level headache centers in Italy OBT-A is used in good compliance with current recommendations. There is agreement about the definition of response as a reduction in headache days by 30% to 50%. Additional effort is required to define response to OBT-A and to establish optimal treatment duration.
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Background OnabotulinumtoxinA (OnabotA) is considered effective in in patients with chronic migraine (CM) who failed on traditional therapies. This study was designed to evaluate the effect of OnabotA injection series on migraine outcome, negative emotional states and sleep quality in patients with CM. MethodsA total of 190 patients with CM (mean (SD) age: 39.3 (10.2) years; 87.9% were female) were included. Data on Pittsburgh sleep quality index (PSQI), headache frequency and severity, number of analgesics used, Migraine Disability Assessment Scale.(MIDAS) scores and Depression, Anxiety and Stress Scale (DASS-21) were evaluated at baseline (visit 1) and 4 consecutive follow up visits, each conducted after OnabotA injection series; at week 12 (visit 2), week 24 (visit 3), week 36 (visit 4) and week 48 (visit 5) to evaluate change from baseline to follow up. ResultsFrom baseline to visit 5, significant decrease was noted in least square (LS) mean headache frequency (from 19.5 to 8.4, p = 0.002), headache severity (from 8.1 to 6.1, p = 0.017), number of analgesics (from 26.9 to 10.4, p = 0.023) and MIDAS scores (from 67.3 to 18.5, p < 0.001). No significant change from baseline was noted in global PSOI and DASS-21 scores throughout the study. Conclusions Our findings revealed that OnabotA therapy was associated with significant improvement in migraine outcome leading to decrease in headache frequency and severity, number of analgesics used and MIDAS scores. While no significant change was noted in overall sleep quality and prevalence of negative emotional states, patients without negative emotional states at baseline showed improved sleep quality throughout the study.
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BACKGROUND: OnabotulinumtoxinA (OnabotA) is effective in Chronic Migraine (CM) during first year of treatment and longer. In real clinical setting, CM patients with acute Medication Overuse (MO) or concurrently receiving oral preventatives are treated with OnabotA. We aim to assess evolution of CM patients beyond first year on OnabotA. METHODS: Data were retrospectively collected in three headache units. We analyzed cases who had received at least five sessions of OnabotA according to PREEMPT protocol. We continued OnabotA therapy when a reduction of number of headache days of at least 30% was achieved. RESULTS: We included 115 patients (98 females, 17 males) who completed 7.6 ± 2.3 (5-13) OnabotA procedures. Previously they had not responded to topiramate and, at least, one other preventative. Age at inclusion was 45.3 ± 12 (14-74) years, and latency between CM onset and OnabotA therapy was 43.1 ± 38.2 (6-166) months. At first OnabotA session 92 patients (80%) fulfilled MO criteria and 107 (93%) received a concurrent oral preventative. In 42 cases (36.5%) OnabotA dose was increased over 155 units. After first year in 57 out of 92 patients (61.9%) MO was discontinued. Among those receiving preventatives, in 52 out of 107 they were retired (48.6%). In 22 cases (19.1%) OnabotA administration was delayed to the fourth or fifth month and in 12 (10.4%) it was temporally stopped. Finally, in 18 patients (15.7%) OnabotA was discontinued due to lack of efficacy beyond first year of treatment. CONCLUSION: Our results suggest that discontinuation of acute medication overuse and oral preventive therapies are achievable objectives in long-term using of OnabotA in CM patients. KEYWORDS: Chronic Migraine; Medication overuse; OnabotulinumtoxinA; Preventatives; Real-life data
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Background: OnabotulinumtoxinA is a treatment specifically approved for the prophylaxis of chronic migraine in adults. The aim of this study was to assess the effectiveness of OnabotulinumtoxinA in chronic migraine after 1 year of treatment in the real-life setting and to identify clinical predictors of outcome. Methods: We designed a prospective multicentre study performed in 13 Hospitals in Spain. Patients underwent a complete medical history and examination. They received treatment with OnabotulinumtoxinA every 12 weeks over a year. Data about outcome, adverse events, abortive medication use, emergency room use and disability were collected at month 3 and 12. Results: Seven hundred and twenty-five subjects completed the study. At 12 months, 79.3% showed >50% reduction in number of headaches per month and 94.9% reported no adverse events. Unilaterality of pain, fewer days of disability per month and milder headache at baseline were correlated with good outcome. Duration of disease <12 months increased the chances of response to treatment with OnabotulinumtoxinA (OR 1.470; CI 95% 1.1.23-2.174, p=0.045). Conclusions: This study confirms effectiveness of treatment with OnabotulinumtoxinA after 1 year of treatment. Chances of having a good outcome may be increased by starting treatment in the first 12 months after chronic migraine diagnosis. This article is protected by copyright. All rights reserved.
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Objective: The aim of this study is to find a relation between several biomarkers in peripheral blood and outcome after treatment with onabotulinumtoxin A (OnabotA). Background: OnabotA is an effective treatment in chronic migraine (CM). Different studies have tried to find predictors of response to treatment, either with clinical characteristics, neuroimaging features, or molecular biomarkers; however, it is still not possible to predict the individual outcome. Methods: We measured serum levels of biomarkers of inflammation (IL-6, IL-10, TNF-α, and hs-CRP), endothelial dysfunction (PTX3 and sTWEAK), blood-brain barrier disruption (cFN), brain damage (S100b, NSE), and trigemino-vascular activation (CGRP) by ELISA in a group of CM patients treated with OnabotA and healthy controls. After 24 weeks, patients were classified in two groups according to their outcome considering variations in headache frequency: nonresponders (nonimprovement or improvement <50%) and responders (improvement >50%). We compared baseline levels of biomarkers between these groups. Results: Sixty-two patients diagnosed with CM (IHS 2013 criteria) who fulfilled criteria for treatment with OnabotA and 24 healthy controls were included. Fifteen patients did not respond to treatment (24.2%) and 47 were responders (75.8%). Pentraxin 3 (PTX3) serum levels (1455.4 ± 487.5 pg/mL versus 720.3 ± 334.1 pg/mL, P < .0001) and calcitonin gene-related peptide (CGRP) serum levels (133.1 ± 86.6 ng/mL versus 58.2 ± 91.7 ng/mL, P = .004) were significantly higher in responders than nonresponders. Serum basal levels of PTX3 >1000 pg/mL (AUC 0.908; 95% CI: 0.827-0.990) and CGRP >50 ng/mL (AUC 0.800; 95% CI: 0.652-0.947) were associated with good response to OnabotA treatment. Conclusions: These results show that molecular markers of trigeminovascular activation (CGRP) and endothelial dysfunction (PTX3) are associated with response to OnabotA and may act as new biomarkers for the selection of treatment in chronic migraineurs.
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The use of Onabotulinumtoxin A as treatment for different neurological conditions is more common in the last decades; its application has been consolidated on the basis of significant clinical results. The clinical experiences with Onabotulinumtoxin A for chronic migraine are on the increase in Italy: at the moment, clinical results are encouraging and enforce the application of the toxin for chronic migraine, according to the results of the PREEMPT studies. The possibility for the patients to be treated with a second cycle of therapy after the first year of treatment is under discussion, in particular for patients who obtained significant clinical benefit from the first period of treatment. In this report, a group of patients treated with Onabotulinumtoxin A for 1 year, according to the PREEMPT protocol, has been retreated for one more year in order to confirm the clinical benefit obtained after the first year of treatment.
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Objective: To evaluate the relationships among modifiable psychological factors and chronic migraine and severe migraine-related disability in a clinic-based sample of persons with migraine. Background: Evidence evaluating relationships between modifiable psychological factors and chronic migraine and severe migraine-related disability is lacking in people with migraine presenting for routine clinical care. Methods: Adults with migraine completed surveys during routinely scheduled visits to a tertiary headache center. Participants completed surveys assessing chronic migraine (meeting criteria for migraine with ≥15 headache days in the past month), severe migraine disability (Migraine Disability Assessment Scale score ≥ 21), and modifiable psychological factors (depressive symptoms [Patient Health Questionnaire-9], anxious symptoms [Generalized Anxiety Disorder-7], Pain Catastrophizing Scale and Headache Specific Locus of Control). Logistic regression evaluated relationships between modifiable psychological factors and chronic migraine and severe migraine disability. Results: Among 90 eligible participants the mean age was 45.0 (SD = 12.4); 84.8% were women. One-third (36.0%) met study criteria for chronic migraine; half of participants (51.5%) reported severe migraine-related disability. Higher depressive symptoms (OR = 1.99, 95% CI = 1.11, 3.55) and chance HSLC (OR = 1.85, 95% CI = 1.13, 1.43) were associated with chronic migraine. Higher depressive symptoms (OR = 3.54, 95%CI = 1.49, 8.41), anxiety symptoms (OR = 3.65, 95% CI = 1.65, 8.06), and pain catastrophizing (OR = 1.95, 95% CI = 1.14, 3.35), were associated with severe migraine-related disability. Conclusions: Psychiatric symptoms and pain catastrophizing were strongly associated with severe migraine-related disability. Depression and chance locus of control were associated with chronic migraine. This study supports the need for longitudinal observational studies to evaluate the relationships among naturalistic variation in psychological factors, migraine-related disability, and migraine chronification.