Migraine Prophylaxis Therapy Research Articles

Sustained benefits of onabotulinumtoxinA treatment in chronic migraine: An analysis of the pooled Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) randomized controlled trials.

To characterize the long-term (56-week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24-week, randomized, double-blind, placebo-controlled phase and a 32-week open-label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double-blind phase (Weeks 21-24; any 12 consecutive weeks; Weeks 13-24) and the entire study (Weeks 53-56; any 12 consecutive weeks; any 4-week period). We assessed the long-term impact on mean monthly headache days and changes from baseline on the six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2.1). We analyzed 1384 participants with chronic migraine (double-blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open-label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56-week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13-24 of the double-blind phase, significantly more onabotulinumtoxinA-treated (386/688 [56.1%]) than placebo-treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25-56, 81.1% (558/688) at Weeks 53-56, and 79.4% (546/688) during any consecutive 12-week period. Mean changes from baseline on the HIT-6 and MSQv2.1 questionnaire surpassed within-group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA-treated participants who achieved <15 monthly headache days during Weeks 21-24 had a greater mean HIT-6 score reduction (-6.5 vs. -1.4) and greater mean MSQv2.1 Role-Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache-related disability and migraine-specific quality of life compared with those who remained at or above the 15-monthly headache days threshold. Sustained benefits observed over 56 weeks support long-term onabotulinumtoxinA use for the prevention of CM.

Injection technique of the upper face with onabotulinumtoxinA in chronic migraine.

The objective is to review the technique of onabotulinumtoxinA injection treatment in the glabellar and frontal regions using the PREEMPT (Phase III REsearch Evaluating Migraine Prophylaxis Therapy) paradigm, with review of the aesthetic issues related to the procedure. OnabotulinumtoxinA is an effective medication for the prevention of chronic migraine. The PREEMPT injection paradigm has been validated in randomized clinical trials and real-world settings. This treatment includes injections in the forehead and glabella area. In addition, for aesthetic uses, glabella onabotulinumtoxinA injections are done in similar muscles specifically the procerus, corrugator supercilii, and frontalis muscles. Often patients who have been injected with onabotulinumtoxinA for chronic migraine have concerns about their appearance and will ask if they can see an aesthetic injector to improve this. This is a difficult issue as onabotulinumtoxinA should be injected with an interval of 10-12 weeks to avoid development of antibodies against onabotulinumtoxinA, so all injections (migraine and aesthetic) should ideally be done close together; however, if an aesthetic injection is done on the same day as a PREEMPT injection, the effect of the PREEMPT injection will not yet be visible as it takes time for onabotulinumtoxinA effects to be seen. Thus, there is a risk of a potential overdose in a particular area if aesthetic injections are done without input from the PREEMPT injector. This is a narrative review supported by photographic documentation showing the technique of onabotulinumtoxinA injection of the upper face, considering anatomical differences between patients, and combining the needs in neurology and aesthetic medicine fields. Practitioners treating chronic migraine often modify some of the principles of the PREEMPT paradigm. Many practitioners are unsure about injections in the glabellar and frontal areas. The authors present a technique for using the PREEMPT protocol and adapting this to the individual patient's anatomy to prevent an unsightly appearance or ptosis. In addition, sites are provided where an aesthetic injector could inject to improve the patient's appearance without overlapping with the PREEMPT injection sites. Adherence to the PREEMPT injection protocol provides an evidence-based approach to achieving clinical benefit for patients with chronic migraine. Aesthetic elements of the treatment of the glabella and forehead require additional attention. The authors provide practical considerations and recommendations regarding this.

Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic

Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. To review the impact of postponing BTX treatment on migraine control. This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

OnabotulinumtoxinA: Still the Present for Chronic Migraine.

OnabotulinumtoxinA (BT-A) is one of the few drugs approved for the preventive treatment of chronic migraine (CM). Despite this, some aspects of its mechanism of action are still a matter of debate, and the precise magnitude of BT-A effects needs to be completely elucidated. BT-A acts primarily upon trigeminal and cervical nerve endings, by inhibiting the release of inflammatory mediators such as calcitonin gene-related peptide, as well as reducing the insertion of ionotropic and metabotropic receptors into the neuronal membrane. These actions increase the depolarization threshold of trigeminal and cervical nerve fibers, thus reducing their activation. The central actions of BT-A are still a matter of debate: a retrograde axonal transport has been postulated, but not clearly assessed in humans. Clinically, the efficacy of BT-A in CM has been assessed by large, randomized placebo-controlled trials, such as the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Those results were also confirmed in a wide range of open-label studies, even for long-term periods. Recently, novel findings have led to a better understanding of its pharmacological actions and clinical usefulness in migraine prevention. This narrative review summarizes, updates and critically revises the available data on BT-A and its possible implementation in chronic migraine. Moreover, the current role of BT-A in CM treatment has been discussed.

The Neuropeptide α-Calcitonin Gene-Related Peptide as the Mediator of Beneficial Effects of Exercise in the Cardiovascular System.

Regular physical activity exerts cardiovascular protective effects in healthy individuals and those with chronic cardiovascular diseases. Exercise is accompanied by an increased plasma concentration of α-calcitonin gene-related peptide (αCGRP), a 37-amino acid peptide with vasodilatory effects and causative roles in migraine. Moreover, mouse models revealed that loss of αCGRP disrupts physiological adaptation of the cardiovascular system to exercise in normotension and aggravates cardiovascular impairment in primary chronic hypertension, both can be reversed by αCGRP administration. This suggests that αCGRP agonists could be a therapeutic option to mediate the cardiovascular protective effects of exercise in clinical setting where exercise is not possible or contraindicated. Of note, FDA has recently approved αCGRP antagonists for migraine prophylaxis therapy, however, the cardiovascular safety of long-term anti-CGRP therapy in individuals with cardiovascular diseases has yet to be established. Current evidence from preclinical models suggests that chronic αCGRP antagonism may abolish the cardiovascular protective effects of exercise in both normotension and chronic hypertension.

The efficacy of botulinum toxin type-A for intractable chronic migraine patients with no pain-free time.

This is a retrospective report of the efficacy of botulinum toxin-A, Botox® (Allergan), in intractable chronic migraine patients non-responsive to previous pharmacological management and with largely no pain-free time, including those with new onset daily persistent headache. Thirty-three patients, all with severe Headache Impact Test (HIT)-6 scores at baseline, received 3-monthly injections of Botox® as per Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PRE-EMPT) protocol over a maximum 33-month period. Response criteria were a sustained reduction of HIT-6 scores below 60. Four patients had headache on at least 20 days a month; the remaining patients had daily headache with no pain-free time, including nine patients with new onset persistent migraine. There was a significant reduction in HIT-6 scores following Botox® therapy (x̅ = -5.45, p = 0.000920). Twenty-one percent of the cohort exhibited a sustained reduction in HIT-6 scores below 60. The number of headache days and pain-free time did not change in five of the six responders, but disability improved. There was no difference between patients with episodic migraine evolving to chronic as opposed to those with chronic migraine from onset. This report suggests that Botox® treatment is efficacious in intractable chronic migraine without pain-free time. The HIT-6 is a reliable and practical parameter to assess disability in this patient group. Use of such validated parameters should be considered with greater weight in future International Classification of Headache Disorders (ICHD) guidelines for controlled clinical trials.

Experience of Botulinum Toxin A Injections for Chronic Migraine Headaches in a Pediatric Chronic Pain Clinic.

Prevalence of chronic migraine in children can reach 7.7%, causing decreased school performance, difficulty with extracurricular activities (including sports, theater, or music), and changes in sleep and mood. Many studies confirm that botulinum toxin type A injections effectively alleviate chronic migraines in adults; however, the literature regarding children is sparse. This study aims to analyze the safety and effectiveness of botulinum type A injections in a group of pediatric patients diagnosed with chronic migraines in a pediatric pain clinic. In this retrospective (2013-2018) study, the effects of botulinum toxin type A injections were analyzed using data from 65 pediatric patients diagnosed with chronic migraines. The study group ranged from 11 to 18 years of age. A pediatric pain management physician administered the botulinum using the Phase 3 Research Evaluating Migraine Prophylaxis Therapy program protocol and followed the pain pattern. Dosages, tolerance, and side effects were measured. In this study, 74% of the patients tried more than 6 medications before the injections. There was a decrease in the visual analog scale score of 5.2 ± 2.2 points upon 6-week follow-up. The mean amount of medication used was 173.2 ± 35 units, and patients received an average of 2.8 ± 1.1 units/kg. Adverse events include one patient who developed dizziness and another who had low-grade fevers with enlarged cervical lymph nodes; both resolved within few minutes. This study supports the use of botulinum type A for chronic migraines in pediatric patients. Multicentered, randomized studies with larger population are needed to evaluate the long-term safety and efficacy of this therapy.

Onabotulinumtoxin A Improves Psychological Aspects in Chronic Migraine Patients.

Background: Chronic migraine (CM) affects 5.4% of the Kuwaiti population. It is associated with significant headache-related disability, psychiatric comorbidity and reduced quality of life. The aim of this study is to assess the efficacy of Onabotulinumtoxin A on psychological aspects of chronic migraine patients.Methods: This prospective study over 36 months included chronic migraine patients in a tertiary headache center. Eligible patients met International Classification of Headache Disorders disorders-third edition, beta version (ICHD-III) revision criteria for chronic migraine. Patients with history of psychiatric or medical problems other than migraine disorders were excluded. Patients who received less than 4 injections cycles of Onabotulinumtoxin A were excluded. Identified patients received 155 units of Onabotulinumtoxin A quarterly according to the Phase III Research Evaluating Migraine Prophylaxis Therapy Trail (PREEMPT) protocol. Quality of life, the seven-item Generalized Anxiety Disorder (GAD-7) scores, the nine-item Patient Health Questionnaire (PHQ9), and the Pittsburgh Sleep Quality Index (PSQI) were collected before injection and at the end of the study. Mean comparison tests were performed using the independent sample t-test to assess the effects of Onabotulinumtoxin A on quality of life and comorbid symptoms of anxiety, depression, and quality of sleep.Results: The study identified 131 chronic migraine patients with a mean age of 44.92 years, mean disease duration of 12.20 years and a mean treatment sessions of 7.58. In their last visit, most of our sample showed improvement in quality of life (81%), GAD-7 (81%), PHQ9 (79%), and PSQ1 (76%). The mean score of patient satisfaction was 7.21. Onabotulinumtoxin A treatment for CM improved quality of life significantly (72.92 vs. 103.62; P < 0.0001). It was also associated with significant reduction in anxiety [GAD-7 (12.00 vs. 6.61; P < 0.0001)] and depression [PHQ-9 (17.91 vs. 12.52; P < 0.0001)] scores, as well as reduced difficulty in sleeping [PSQI (12.60 vs. 6.66; P < 0.0001)] at the last visit.Conclusion: Prophylactic Onabotulinumtoxin A treatment for CM was associated with significant improvement of quality of life, reduction in symptoms of anxiety and depression, as well as improved symptoms of poor sleep.

Method of onabotulinumtoxin type A injection in chronic migraine: the PREEMPT protocol in clinical practice

Chronic migraine (CM), a condition where patients experience over 15 days of headache per month, was identified as a separate disease in the International Classification of Headache Disorders 3-beta version. Onabotulinumtoxin type A was approved for the treatment of CM in 2010 after the completion of the extensive PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) clinical program. The efficacy of onabotulinumtoxin type A was demonstrated in numerous studies in CM and medication-overuse headache. The paper focuses on the PREEMPT injection paradigm and provides guidance for successful and safe treatment of CM.

OnabotulinumtoxinA injection in the treatment of chronic migraine.

The earliest descriptions of botulism were in the early 19th century, and was reported by the German physician Justinus Kerner. The term "botulism" was derived from the Latin word botulus, indicating its original association with sausages. It took another 150 years or so to come into clinical use. The first clinical application was strabismus, and was developed by the American ophthalmologist Alan B. Scott, whose effort led to the pharmaceutical product known as onabotulinumtoxinA today. The therapeutic benefit in migraine was an incidental finding in a report by the American plastic surgeon William J. Binder, which inspired a series of clinical studies in headache disorders. The doses and injection techniques in the earlier reports were variable, so were the results. It was until the Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) 1 and 2 studies when its efficacy and safety, as well as the indication, i.e., chronic migraine (CM), were ascertained. Even though there were criticisms regarding the heterogeneities in the results between the PREEMPT 1 and 2 studies, the data on efficacy endpoints and safety were generally consistent, which were subsequently confirmed by the open-label extension of the PREEMPT 1 and 2 studies, and three open-label studies, namely the Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL), the REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilization, and Patient-reported OutcomeS observed in practice (REPOSE) studies, and the CM Post-Authorization Safety Study (CM PASS) studies. On the other hand, the results were challenged by the Chronification and Reversibility of Migraine (CHARM) study, which involved CM patients with medication overuse. It was concluded that the clinical improvement was attributed to early withdrawal of the overused acute medications, rather than onabotulinumtoxinA injections. However, fundamental differences in the patient profile and methodology between the CHARM and PREEMPT studies existed, and cautious should be exercised when interpreting and comparing the results. According to the practical guidelines and reimbursement regulations in many countries, its use is limited to CM patients, and is reserved for those who fail at least 2-3 preventive medications, due to either lack of efficacy or intolerability. Cessation of treatment is recommended in patients who do not respond to 2-3 injection cycles, or in patients whose headache frequency has dropped to <10-15 days a month. Even in the era of calcitonin-gene-related peptide monoclonal antibodies, onabotulinumtoxinA injection remains a treatment option of reasonable cost-effectiveness in carefully selected patients.

Efficacy of Multi-Modal Migraine Prophylaxis Therapy on Hyperacusis Patients.

To evaluate the efficacy of a multi-modal migraine prophylaxis therapy for patients with hyperacusis. In a prospective cohort, patients with hyperacusis were treated with a multi-modal step-wise migraine prophylactic regimen (nortriptyline, verapamil, topiramate, or a combination thereof) as well as lifestyle and dietary modifications. Pre- and post-treatment average loudness discomfort level (LDL), hyperacusis discomfort level measured by a visual analogue scale (VAS), and scores on the modified Khalfa questionnaire for severity of hyperacusis were compared. Twenty-two of the 25 patients (88%) reported subjective resolution of their symptoms following treatment. Post-treatment audiograms showed significant improvement in average LDL from 81.3 ± 3.2 dB to 86.4 ± 2.6 dB (P < .001), indicating increased sound tolerability. The VAS discomfort level also showed significant improvement from a pre-treatment average of 7.7 ± 1.1 to 3.7 ± 1.6 post-treatment (P < .001). There was also significant improvement in the average total score on modified Khalfa questionnaire (32.2 ± 3.6 vs 22.0 ± 5.7, P < .001). The majority of patients with hyperacusis demonstrated symptomatic improvement from migraine prophylaxis therapy, as indicated by self-reported and audiometric measures. Our findings indicate that, for some patients, hyperacusis may share a pathophysiologic basis with migraine disorder and may be successfully managed with multimodal migraine prophylaxis therapy.

Early onset of effect of onabotulinumtoxinA for chronic migraine treatment: Analysis of PREEMPT data.

The Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials demonstrated efficacy/tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis assessed time of onset of onabotulinumtoxinA after the first treatment in total and responder populations and consistency weekly through five treatment cycles. In the 24-week, double-blind, placebo-controlled phase of PREEMPT, individuals were randomized 1:1 to onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for two cycles. The primary pooled efficacy variable was change in headache days per 28 days at week 24. We assessed change in headache and migraine/probable migraine (hereafter migraine) days/week compared with baseline week 4. Baseline mean (SD) headache days/week (week 4 of baseline) for onabotulinumtoxinA (n = 688) and placebo (n = 696) were similar (4.8 [1.6] vs. 4.8 [1.6] days/week, respectively), as were migraine days/week (4.6 [1.7] vs. 4.6 [1.7] days/week). The effect of onabotulinumtoxinA on change in headache and migraine days/week was significantly greater than placebo at week 1, persisting from week 3 after the first treatment (-1.6 [2.2] vs. -1.1 [2.2] headache days/week [ p < 0.001] and -1.6 [2.2] vs. -1.1 [2.2] migraine days/week [ p < 0.001]). Headache and migraine days decreased in onabotulinumtoxinA responders beginning 1 week after treatment 1. Treatment with onabotulinumtoxinA is associated with significant reductions in headache and migraine days/week at week 1, persisting after week 3, compared with placebo. Combined with earlier reports showing onabotulinumtoxinA treatment results in a persistent and progressive reduction in headache days over 56 weeks, it is suggested peak benefit may require multiple treatments. ClinicalTrials.gov: NCT00156910 and NCT00168428.

Response to BotulinumtoxinA in a migraine cohort with multiple comorbidities and widespread pain

BackgroundThe phase III research evaluating migraine prophylaxis therapy (PREEMPT) protocol was developed in low-risk migraine patients. We studied longitudinal response to treatment in a sequential retrospective observational cohort to evaluate...

Evaluating Quality of Life in Patients With Meniere's Disease Treated as Migraine.

To evaluate the change in quality of life (QOL) of patients with Meniere's disease (MD) after treatment with migraine prophylaxis therapy. Patients with definite MD were given the Meniere's Disease Outcomes Questionnaire-Retrospective (MDOQ-R) after migraine prophylactic therapy to assess QOL. Changes in physical, emotional, and social parameters affected by MD were calculated, along with a global pre- and posttreatment QOL scores. The MDOQ-R was given to 27 consecutive patients with definite MD. Patients who had at least an 18-month follow-up were included, resulting in 25 questionnaires. The mean change in QOL score was 25 ± 16 (range, -3 to 55), P = .02. Quality of life was improved in 23 (92%) of the respondents in every metric measured, unchanged in 1 (4%), and poorer in 1 (4%) of patients after migraine prophylaxis treatment. Majority of MD patients who had all failed diuretic therapy responded positively to medications used for migraine prophylaxis, as indicated by a significant improvement in QOL. This study may further suggest a correlation between the pathophysiologic basis of disease in MD and vestibular migraine. Patients with MD may be successfully managed with medications intended to treat migraine.

OnabotulinumtoxinA in the treatment of patients with chronic migraine: clinical evidence and experience.

Chronic migraine is a debilitating neurobiological disorder that affects approximately 1.4–2.2% of the population worldwide. Patients with chronic migraine have 15 or more headache days per month, with at least 8 days per month that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a standardized injection protocol, was approved by the US Food and Drug Administration in 2010 for the treatment of chronic migraine. The approval was made based on results from two large, randomized, double-blind placebo-controlled trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. Since then, numerous studies have been performed investigating the short-term and long-term benefits, risks and complications of the use of onabotulinumtoxinA injections for the treatment of chronic migraine. The purpose of this narrative review is to describe the currently available clinical evidence for the use of onabotulinumtoxinA injections for treating patients with chronic migraine.

Onabotulinum toxin A in the treatment of chronic migraine: patient selection and special considerations.

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.

The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled analysis

BackgroundOnabotulinumtoxinA has been shown to reduce headache-days among patients with chronic migraine (CM). The objective of this analysis was to determine whether onabotulinumtoxinA has an impact on headache-day severity in patients with CM among those patients who were deemed non-responders based on reduction in the frequency of headache days alone.MethodsData from the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trial program (a 24-week, 2-treatment cycle, double-blind, randomized, placebo-controlled, parallel-group phase, followed by a 32-week, 3-treatment cycle, open-label phase) were pooled for analysis. Patients kept a daily diary to record headache severity on a 4-point scale (from none to severe), and a 6-domain Headache Impact Test (HIT-6) was used to determine the clinical impact of headaches. Analysis was undertaken to assess whether the subset of patients that were headache-day frequency non-responders at week 24 (patients with <50% reduction in headache-day frequency) experienced a reduction in headache severity whilst receiving onabotulinumtoxinA.ResultsFor headache-day frequency non-responders, significant reductions in the number of severe headache days, average daily headache severity, pooled percentage of severe headache days and headache severity score were observed at week 24 for patients who had received onabotulinumtoxinA compared with those who had received placebo. The between-group differences were reduced and non-significant at week 56. Similarly, headache-day frequency non-responders receiving onabotulinumtoxinA were found to have an improvement in the clinical impact of headaches using results from the HIT-6.ConclusionsThese results suggest that even those patients with CM who are deemed non-responders based on analysis of headache frequency alone experience clinically meaningful relief from headache intensity following treatment with onabotulinumtoxinA.

Quarterly repeat cycles of onabotulinumtoxinA in chronic migraine patients: the benefits of the prolonged treatment on the continuous responders and quality-of-life conversion rate in a real-life setting

OnabotulinumtoxinA was approved for treatment of chronic migraine (CM) after publication of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. However, the PREEMPT trials lasted only up to 1 year. The main aim of our retrospective study was to evaluate whether a prolonged treatment of onabotulinumtoxinA (18 months, six quarterly cycles) will sustain or further improve the efficacy results and the quality of life achieved at 6 and 12 months. Patients were adults with CM with or without overuse of drugs, with at least six regularly repeat onabotulinumtoxinA treatments, administered according to the PREEMPT protocol. The outcomes were investigated after 6, 12, and 18 months of treatment with respect to baseline and with respect to each previous study time point. Headache days and hours, and dosage of headache medication taken with latency period, were collected from the patients daily. Quality of life was evaluated by means of the Migraine Disability Assessment (MIDAS) questionnaire. At each study time point, the proportion of responder patients with respect to baseline was evaluated. For all measures, the baseline data were referred to the previous month before starting. Forty-seven patients were evaluated. Our data show a decrease in the monthly headache days and hours, at each study evaluation, with respect to the previous one. They showed that beyond the first year, a statistically significant difference in the monthly days of headache compared at 18 vs. 12 months is observed. A significantly higher proportion of patients (with a response greater than 75% decrease from baseline in the frequency of headache days and hours) was observed at month 18 compared to month 12. The proportion of patients in MIDAS grade I increased over time, and a statistically significant improvement in MIDAS I score was obtained from month 12 to month 18. A positive modification in the consumption of analgesics over time was observed (p for trend <0.001). The mean acute drug latency strongly decreased over time. Our study confirmed that onabotulinumtoxinA is an effective treatment to reduce headache-related disability and improve patients’ quality of life, highlighting that upon repeated administration, the therapy efficacy increases significantly and a progressive trend of “first-time response” is observed for the entire period under consideration.

Insights into the Functional Anatomy Behind the PREEMPT Injection Paradigm: Guidance on Achieving Optimal Outcomes.

ObjectiveTo provide clinically relevant insights on the identification of the muscles and techniques involved in the safe and effective use of onabotulinumtoxinA for chronic migraine prophylaxis.BackgroundAlthough guidance on the use of onabotulinumtoxinA for chronic migraine is available, based on the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program, clinical experience has shown that insufficient understanding of the anatomy and function of the head and neck muscles may lead to undesirable outcomes and suboptimal efficacy.Design/MethodsEach muscle involved in the standardized PREEMPT injection paradigm is reviewed with a thorough description of each muscle's anatomy (ie, muscle description and location, innervation, vascular supply) and function. Key insights based on clinical experience are also provided to help improve outcomes.ResultsThe identification of the muscles in the PREEMPT injection paradigm should be based on each patient's unique anatomy and injections should be administered using the advised techniques. A thorough examination of the patient prior to treatment is also critical to determine if any preexisting conditions may increase the risk for unwanted outcomes and appropriate expectations should be communicated.ConclusionsThorough knowledge of the functional anatomy of the muscles involved in the standardized PREEMPT injection paradigm is critical to achieve the efficacy and safety observed in clinical trials. In addition, it is important to assess a patient's baseline condition to anticipate the risk for unwanted outcomes that may result from treatment.

Anatomical Regional Targeted (ART) BOTOX Injection Technique: A Novel Paradigm for Migraines and Chronic Headaches.

Migraine headaches are a debilitating disease that causes significant socioeconomic problems. One of the speculated etiologies of the generation of migraines is peripheral nerve irritation at different trigger points. The use of Onabotulinum toxin A (BOTOX), although initially a novel approach, has now been determined to be a valid treatment for chronic headaches and migraines as described in the Phase III Research Evaluating Migraine Prophylaxis Therapy trials that prompted the approval by the Food and Drug Administration for treatment of chronic migraines. The injection paradigm established by this trial was one of a broad injection pattern across large muscle groups that did not always correspond to the anatomical locations of nerves. The senior author developed the Anatomical Regional Targeted BOTOX injection paradigm as an alternative to the current injection model. This technique targets both the anatomical location of nerves known to have causal effects with migraines and the region where the pain localizes, to provide relief across a wide distribution of the peripheral nerve. This article serves as a guide to the Anatomical Regional Targeted injection technique, which, to our knowledge, is the first comprehensive BOTOX injection paradigm described in the literature for treatment of migraines that targets nerves and nerve areas rather than purely muscle groups. This technique is based on the most up-to-date anatomical and scientific studies and large-volume migraine surgery experience.