Treatment Of Chronic Migraine Research Articles

Bilateral Greater Occipital Nerve Block for Preventing the OnabotulinumtoxinA Wear-off Phenomenon in the Treatment of Chronic Migraine: A Case Series of 12 Patients

Purpose: OnabotulinumtoxinA is widely used to treat chronic migraines; however, the wear-off phenomenon before the next scheduled dose has emerged as a challenge. This study suggests a new strategy for preventing the wear-off phenomenon using bilateral greater occipital nerve block. Methods: We conducted a retrospective review of patients diagnosed with chronic migraine who were treated with onabotulinumtoxinA and bilateral greater occipital nerve block at St. Vincent Hospital from January 2023 to December 2023. Twelve chronic migraine patients with a history of the wear-off phenomenon received a greater occipital nerve block 8 weeks after the initial onabotulinumtoxinA injection for two sessions. Responses to treatment were evaluated with regular follow-ups and daily headache diaries. Results: All patients who had previously experienced the wear-off phenomenon with conventional onabotulinumtoxinA treatment did not experience the wear-off phenomenon during two sessions with an additional greater occipital nerve block administered 8 weeks after each onabolulinumtoxinA injection. Conclusion: Bilateral greater occipital nerve block administered 8 weeks after the initial onabotulinumtoxinA injection effectively prevents the wear-off phenomenon, enabling sustained therapeutic benefits in chronic migraine patients. Further research is needed to confirm these findings in larger cohorts.

Typical clinical practice of treating patients with chronic migraine

Currently, effective methods for the treatment of chronic migraine (CM) have been developed, but it remains unclear how they are used in real clinical practice and how often. The typical practice of treating patients with CM in our country has not been sufficiently investigated, which formed the basis for conducting this study.Objective: to evaluate the quality of treatment of patients with CM in real-life neurological practice.Material and methods. The study included 200 patients with CM (63 men and 137 women, mean age – 33.1±7.1 years) admitted to A.Ya. Kozhevnikov Clinic of Nervous Diseases (CND) of Sechenov University for frequent headaches, who were previously treated by neurologists in other medical institutions on an outpatient and/or inpatient basis. All patients were clinically interviewed to establish a diagnosis and analyze their previous treatment.Results. All patients had an experience of incorrect or inadequate treatment, including ineffective drug and non-drug methods. All patients were taking painkillers to relieve migraine, but less than half of them was satisfied with their effectiveness. Only 12 (8.5%) patients with medication overuse headache had previously received treatment for drug overuse. None of the patients who were admitted to CND had previously received cognitive-behavioral therapy and treatment with an interdisciplinary approach that included not only pharmacotherapy but also psychological and behavioral methods and kinesiotherapy.Conclusion. In real-life clinical practice, ineffective methods are often used to treat migraine, and an interdisciplinary approach that includes effective pharmacotherapy and non-pharmacological methods is lacking.

Real-World Evidence of the Safety and Effectiveness of Atogepant Added to OnabotulinumtoxinA for the Preventive Treatment of Chronic Migraine: A Retrospective Chart Review.

Combination use of atogepant and onabotulinumtoxinA has the potential to be more effective than either alone for the preventive treatment of chronic migraine (CM) due to their complementary mechanisms of action. This analysis collected real-world data to evaluate the safety, tolerability, and effectiveness of adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM. This retrospective, longitudinal, multicenter chart review included adults with CM who received ≥ 2 consecutive cycles of onabotulinumtoxinA before ≥ 1month of onabotulinumtoxinA and atogepant combination treatment. Charts at atogepant prescription (index date) and two subsequent onabotulinumtoxinA treatment visits (~ 3 and ~ 6 months post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥ 50% reduction in MHDs, discontinuation rates, and adverse events (AEs). Of the 55 charts that met safety analysis criteria, 31 had data on headache days at index and first post-index visit and were eligible for effectiveness analysis (mean age 46.7years, 94.5% female). For those with data available prior to onabotulinumtoxinA treatment (n = 25), the mean MHD was 24.0 days, reduced by 8.15 days after onabotulinumtoxinA treatment. After atogepant was added, MHD was incrementally reduced by 4.53 days and 8.75 days from index date to the first (N = 31) and second (N = 23) post-index onabotulinumtoxinA treatment visit, respectively. A ≥ 50% reduction in MHDs was achieved by 45.2% of patients ~ 3months post-index. Atogepant and onabotulinumtoxinA were discontinued by 16.1% and 6.5% of patients, respectively. In the safety population, 32.7% of patients experienced ≥ 1 AE. No serious AEs were reported. This real-world study of patients with CM demonstrated that adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM was effective by providing an additional reduction in MHDs over ~ 3 and ~ 6months of combination treatment. Safety results were consistent with the known safety profiles of onabotulinumtoxinA and atogepant, with no new safety signals identified.

Genetic variants associated with response to anti-CGRP monoclonal antibody therapy in a chronic migraine Han Chinese population

BackgroundAnti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine.MethodsWe conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database.ResultsSix single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure.ConclusionThe identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology.Trial registrationNot applicable.

Insights from 25 years of onabotulinumtoxinA in migraine - mechanisms and management.

OnabotulinumtoxinA (BTX-A) was first linked to beneficial effects in migraine 25 years ago and was approved by the FDA for preventive treatment of chronic migraine in 2010. The treatment has since had a major impact on the well-being of people with chronic migraine. The clinical development programme for BTX-A and research since its approval have provided insights into the neuromodulatory sensory effect of BTX-A, how it can control chronic migraine despite its peripheral action, and the underlying biology of migraine as a disease. In this Review, we consider the impact that BTX-A has had on the management of chronic migraine and on the research field. We discuss the insights provided by clinical research, encompassing the clinical trials and subsequent real-world evidence, and the mechanistic insights provided by preclinical and translational research. We also provide an overview of future directions of research in the field BTX-A in migraine and the clinical translation of this research.

Efficacy of Atogepant in Chronic Migraine With and Without Acute Medication Overuse in the Randomized, Double-Blind, Phase 3 PROGRESS Trial.

Atogepant is an oral, calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine. We evaluated the efficacy of atogepant for the preventive treatment of chronic migraine (CM) in participants with and without acute medication overuse. This subgroup analysis of the phase 3, 12-week, randomized, double-blind, placebo-controlled PROGRESS trial evaluated adults with a ≥1-year history of CM, ≥15 monthly headache days (MHDs), and ≥8 monthly migraine days (MMDs) during the 4-week baseline period. Participants were randomized (1:1:1) to placebo, atogepant 30 mg twice daily (BID), or atogepant 60 mg once daily (QD) for 12 weeks and were analyzed by acute medication overuse status (triptans/ergots for ≥10 days per month, simple analgesics for ≥15 days per month, or combinations of triptans/ergots/simple analgesics for ≥10 days per month). Outcomes included change from baseline in mean MMDs, MHDs, and monthly acute medication use days; ≥50% reduction in mean MMDs across 12 weeks; and patient-reported outcome (PRO) measures. Of 755 participants in the modified intent-to-treat population, 500 (66.2%) met baseline acute medication overuse criteria (placebo, n = 169 [68.7%]; atogepant 30 mg BID, n = 161 [63.6%]; atogepant 60 mg QD, n = 170 [66.4%]). The least squares mean difference (LSMD) (95% CI) from placebo in MMDs was -2.7 (-4.0 to -1.4) with atogepant 30 mg BID and -1.9 (-3.2 to -0.6) with atogepant 60 mg QD. Mean MHDs (LSMD [95% CI] -2.8 [-4.0 to -1.5] and -2.1 [-3.3 to -0.8]) and mean acute medication use days (LSMD [95% CI] -2.8 [-4.1 to -1.6] and -2.6 [-3.9 to -1.3]) were reduced and a higher proportion of participants achieved ≥50% reduction in MMDs (odds ratio [95% CI] 2.5 [1.5-4.0] and 2.3 [1.4-3.7]) with atogepant 30 mg BID and atogepant 60 mg QD. There was a 52.1%-61.9% reduction in the proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks. Atogepant improved PRO measures. Similar results were observed in the subgroup without acute medication overuse. Atogepant was effective in participants with CM, with and without acute medication overuse, as evidenced by reductions in mean MMDs, MHDs, and acute medication use days; reductions in the proportion of participants meeting acute medication overuse criteria; and improvements in PROs. ClinicalTrials.gov NCT03855137. Submitted: February 25, 2019; first patient enrolled: March 11, 2019. clinicaltrials.gov/ct2/show/NCT03855137. This study provides Class II evidence that atogepant reduces mean MMDs, MHDs, and monthly acute medication use days in adult patients with or without medication overuse.

Additional effect of erenumab for patients with chronic migraine treated with onabotulinumtoxin A-real-world data from a preliminary cohort study.

This preliminary retrospective cohort study investigates the potential additive prophylactic effect of erenumab, a fully human monoclonal antibody that blocks the calcitonin gene-related peptide receptor, in combination with ongoing onabotulinumtoxin A (onaBoNT-A) treatment in patients suffering from chronic migraine. The study included 218 patients and investigated the effects of adding erenumab to the existing treatment regimen. The primary outcome was the MIDAS (Migraine Disability Assessment) score assessed 3 months after the introduction of erenumab. The results indicated a significant improvement of the MIDAS score, suggesting a reduction in migraine-related disability following the addition of erenumab to onaBoNT-A. In the inter group comparison, dual therapy showed a significantly greater reduction of the MIDAS when compared to a switch from onaBoNT-A to erenumab monotherapy, but not compared to initiation of onaBoNT-A monotherapy. It is hypothesized that the observed additive effects are due to the independent modes of action of erenumab and onabotulinumtoxin A. This study suggests that the combination of erenumab with onaBoNT-A may offer an improved approach for the treatment of chronic migraine in selected patients. However, the results highlight the need for prospective, controlled studies to validate these findings and determine the optimal combination of treatments tailored to the individual patient.

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.

The effectiveness and predictors influencing the outcome of onabotulinumtoxinA treatment in chronic migraine: understanding from diverse patient profiles in a single session.

This real-world study aimed to investigate how onabotulinumtoxinA affects the outcome of migraine, along with accompanying anxiety, depression, and bruxism among a group of patients with chronic migraine (CM) and define predictors of good response. Patients diagnosed with CM who received onabotulinumtoxinA were included in this single-center, real-world retrospective cohort study. Monthly headache days (MHDs), monthly migraine days (MMDs), headache intensity (numeric rating scale-NRS) and headache characteristics were evaluated at baseline and 12 weeks post-treatment. Patient-reported outcome measures (PROMs) included Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6) scores, 12-item Allodynia Symptom Checklist (ASC-12), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Response to onabotulinumtoxinA (% reduction in MHDs) and treatment-related adverse events (TRAEs) were also evaluated. OnabotulinumA was applied to the masseter muscles in patients complaining of bruxism. A total of 72 patients (mean ± SD age: 36.3 ± 8.5 years; 91.7% were female) diagnosed with CM were included. OnabotulinumtoxinA revealed significant decrease in median (IQR) MHDs [from 20(15-25) at baseline to 6(4-10), p < 0.001], MMDs [from 9(6-12) to 3(1-6), p < 0.001] and NRS [from 9(8-10) to 7(6-8), p < 0.001], and the MIDAS [from 54(30-81) to 16(7-24), p < 0.001], HIT-6 [from 67(65-69) to 58(54-64), p < 0.001], ASC-12 [from 6(1.5-9) to 2(0-9), p = 0.002], BAI [from 12(6.5-19) to 9(3-17), p < 0.001] and BDI [from 11(6.5-17) to 3(2-7) p < 0.001] scores at 12 weeks post-treatment. Patients complaining of bruxism received onabotulinumtoxinA injections in the first n = 27 (37.5%) and 12. week post-treatment n = 19 (70.4%) periods. Overall, 70.8% of patients responded (≥50% reduction in MHDs), while 29.2% did not (<50% reduction). Both groups showed similar characteristics in demographics, migraine history, baseline PROMs scores, comorbidities, and prior treatments. OnabotulinumtoxinA is an effective treatment option that rapidly improves migraine outcomes, disability, and impact while also alleviating comorbid depression and/or anxiety. This study's noteworthy finding is that onabotulinumtoxinA is effective in a majority of CM patients, irrespective of their prior treatment history, migraine characteristics, or concurrent comorbidities. Furthermore, we identified no specific predictors for a favorable response to onabotulinumtoxinA. Applying onabotulinumtoxinA to the masseter muscles can relieve discomfort associated with concurrent bruxism; however, it does not impact migraine outcomes.

Dopamine D2 Receptor Activation Blocks GluA2/ROS Positive Feedback Loop to Alienate Chronic-Migraine-Associated Pain Sensitization.

Chronic migraine is a disabling disorder without effective therapeutic medicine. AMPA receptors have been proven to be essential to pathological pain and headaches, but the related regulatory mechanisms in chronic migraine have not yet been explored. In this study, we found that the level of surface GluA2 was reduced in chronic migraine rats. Tat-GluR23Y (a GluA2 endocytosis inhibitor) reduced calcium inward flow and weakened synaptic structures, thus alleviating migraine-like pain sensitization. In addition, the inhibition of GluA2 endocytosis reduced the calcium influx and alleviated mitochondrial calcium overload and ROS generation in primary neurons. Furthermore, our results showed that ROS can induce allodynia and GluA2 endocytosis in rats, thus promoting migraine-like pain sensitization. In our previous study, the dopamine D2 receptor was identified as a potential target in the treatment of chronic migraine, and here we found that dopamine D2 receptor activation suppressed chronic-migraine-related pain sensitization through blocking the GluA2/ROS positive feedback loop in vivo and in vitro. Additionally, ligustrazine, a core component of ligusticum chuanxiong, was shown to target the dopamine D2 receptor, thereby alleviating ROS production and abnormal nociception in CM rats. This study provides valuable insight into the treatment of chronic migraine.

Light Therapy in Chronic Migraine.

This review assesses the effectiveness and safety of light therapy, particularly green light therapy, as an emerging non-pharmacological treatment for chronic migraine (CM). It aims to highlight alternative or complementary approaches to traditional pharmacological remedies, focusing the need for diverse treatment options. Despite sensitivity to light being a defining feature of migraine, light therapy has shown promising signs in providing substantial symptom relief. Studies have provided insights into green light therapy's role in managing CM. These studies consistently demonstrate its efficacy in reducing the frequency, severity, and symptoms of migraines. Additional benefits observed include improvements in sleep quality and reductions in anxiety. Importantly, green light therapy has been associated with minimal side effects, indicating its potential as a suitable option for migraine sufferers. In addition to green light, other forms of light therapy, such as infrared polarized light, low-level laser therapy (LLLT), and intravascular irradiation of blood (ILIB), are also being explored with potential therapeutic effects. Light therapies, especially green light therapy, are recognized as promising, safe, and non-pharmacological interventions for treating CM. They have been shown to be effective in decreasing headache frequency and enhancing the overall quality of life. However, current studies, often limited by small sample sizes, prompt more extensive clinical trials to better understand the full impact of light therapies. The exploration of other light-based treatments, such as LLLT and ILIB, warrants further research to broaden the scope of effective migraine management strategies.

Acupuncture plus topiramate placebo versus topiramate plus sham acupuncture for the preventive treatment of chronic migraine: A single-blind, double-dummy, randomized controlled trial.

Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine. This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100 mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12. Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, p = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, p = 0.007]). No severe adverse events were reported. Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine. ISRCTN.org Identifier 13563102.

Botulinum Treatment Induced Dropped Head Syndrome in a Patient With Chronic Migraines and Multiple Sclerosis

BACKGROUND: Chronic migraine treatment typically is treated medically by use of medications, such as nonsteroidal anti-inflammatory drugs and triptans; however, for a subset of patients, botulinum toxin (or Botox) has effectively been shown to be an alternative medication. CASE REPORT: Following Botox administration for chronic headaches, our patient developed unforeseen adverse effects and presented with severe neck stiffness, facial droop, and dysphagia, collectively known as dropped head syndrome, prompting them to seek emergency care. In order to counteract botulinum toxicity, we administered neostigmine, but unexpectedly induced cholinergic toxicity, which led to severe secretions and blurry vision. Glycopyrrolate was administered with responsive resolution of symptoms. CONCLUSIONS: This case highlights the complexities of managing adverse reactions to Botox and raises considerations for alternative treatments, such as atropine, or concurrent neostigmine treatment with glycopyrrolate. KEY WORDS: Botox, botulinum, dropped head syndrome, chronic migraine, migraine, multiple sclerosis

P.004 Real-world effectiveness of intravenous eptinezumab in patients with chronic migraine and previous subcutaneous preventive migraine treatment

Background: Since 2018, several CGRP-targeted therapies have entered the migraine market, including eptinezumab. Minimal evidence exists evaluating the real-world effectiveness of switching from a subcutaneous to an intravenous anti-CGRP mAb. Methods: An observational, multi-site (n=4), US-based study, REVIEW evaluated real-world experiences of patients with chronic migraine (CM) treated with eptinezumab using a chart review, patient survey, and physician interviews. Adults (≥18 years) with a diagnosis of CM who had completed ≥2 consecutive eptinezumab infusion cycles were eligible. Results: Enrolled patients were primarily female (83%, 78/94), had a mean age of 49 years and a mean migraine diagnosis duration of 15.4 years. All patients (94/94) self-reported prior preventive therapy with 89% (84/94) reporting prior subcutaneous anti-CGRP mAb use (i.e., fremanezumab, galcanezumab, or erenumab). Regardless of prior exposure to a CGRP ligand or receptor blocker, the number of “good” days/month more than doubled following eptinezumab. Patients experienced a similar mean change in the number of “good” days/month regardless of the number and type of previous subcutaneous anti-CGRP mAb used. Conclusions: This real-world, patient survey showed that patients with prior exposure to subcutaneous anti-CGRP mAbs had high overall satisfaction with the effectiveness of eptinezumab treatment regardless of the number and type of previous therapies used.

Cost Effectiveness of Fremanezumab in Episodic and Chronic Migraine Patients from a Japanese Healthcare Perspective.

Fremanezumab is an effective treatment for episodic (EM) and chronic migraine (CM) patients in Japan, but its cost effectiveness remains unknown. The objective of this study was to determine the cost effectiveness of fremanezumab compared with standard of care (SOC) in previously treated EM and CM patients from a Japanese healthcare perspective. Estimated regression models were implemented in a probabilistic Markov model to inform effectiveness and health-related quality-of-life data for fremanezumab and SOC. The model was further populated with data from the literature. The adjusted Japanese healthcare perspective included productivity losses. The main model outcomes were quality-adjusted life-years (QALYs), costs (2022 Japanese Yen [¥]), and incremental outcomes including the incremental cost-effectiveness ratio (ICER). Analyses were performed separately for the EM and CM patients and combined. Costs and effects were discounted at an annual rate of 2.0%. The mean QALYs over a 25-year time horizon for the EM and CM populations combined were 13.03 for SOC and 13.15 for fremanezumab. The associated costs were ¥27,550,292 for SOC and ¥28,371,048 for fremanezumab. QALYs were higher and costs lower for EM patients compared with CM patients for both fremanezumab and SOC. The deterministic ICERs of fremanezumab versus SOC were ¥6,334,861 for EM, ¥7,393,824 for CM, and ¥6,530,398 for EM and CM combined. Indirect costs and choice of mean migraine days model distribution had a substantial impact on the ICER. Using fremanezumab in a heterogeneous mixture of Japanese EM and CM patients resulted in a reduction of monthly migraine days and thus more QALYs compared with SOC. The cost effectiveness of fremanezumab versus SOC in EM and CM patients resulted in an ICER of ¥6,530,398, from an adjusted Japanese public healthcare perspective.

Multimodal digital health treatments for Chronic Migraine associated with Medication Overuse Headache: a literature appraisal and results of a single-arm open trial (the BE-HOME program).

Mindfulness-based treatments gained popularity for migraine treatment. In this manuscript we report the results of a single-arm open pilot study that evaluated the impact of a multimodal web-based intervention combining home-based medication withdrawal, patients' education, and online mindfulness-based interventions. We aimed to address whether our program had the ability to show a change in the observed parameters and the study should therefore be intended as an early phase trial. Consecutive patients with chronic migraine associated with medication overuse headache were enrolled, followed-up for 12months, in a program that included home-based medication withdrawal, education on the correct use of drugs and lifestyle issues, prescription of tailored pharmacological prophylaxis, and attendance to six online mindfulness-based sessions. We tested the effect of the program on improving headache frequency, medication intake, quality of life (QoL), headache impact, depression, self-efficacy, and pain catastrophizing. A total of 37 patients completed the study (10 dropped out). We observed a large improvement in headache frequency, medication intake, headache impact, and QoL, a moderate improvement in pain catastrophizing and a mild improvement in depression symptoms; 70% to 76% of patients achieved 50% or more reduction in headache frequency from baseline to each follow-up (p < .01). The results of our multimodal program showed significant improvements in headache frequency, medication intake, and patient-reported outcomes. Future studies are needed to better identify patients who might benefit most from Digital Health Interventions and to demonstrate at least an equivalence in outcome with in-person programs carried out in hospital settings.

Sequential administration of peripheral nerve blocks andonabotulinumtoxinA for the treatment of chronic migraine andother headache disorders-A retrospective tolerability and safety study.

To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Letter to editor for raising awareness for cutting-edge Treatments for chronic Migraine ‘’Use of CGRP Inhibitors, TMS and Relaxation Techniques "

Chronic migraine is defined as headaches occurring on at least 15 days per month characterized by higher disability and incidence of comorbidities in comparison to episodic migraine. It is a debilitative neurological disorder that impacts on average 1.4-2.25% of the global population and imposes a significant individual and socioeconomic burden .

A Systematic Review of Clinical Outcomes Utilizing Combined Occipital Nerve (ONS) and Supraorbital Nerve (SON) Stimulation in the Treatment of Chronic Migraine (P7-12.008)

A Systematic Review of Clinical Outcomes Utilizing Combined Occipital Nerve (ONS) and Supraorbital Nerve (SON) Stimulation in the Treatment of Chronic Migraine (P7-12.008)

Clinical Effectiveness of Rimegepant with Onabotulinum Toxin type A in treatment of Chronic Migraine (P7-12.010)

Clinical Effectiveness of Rimegepant with Onabotulinum Toxin type A in treatment of Chronic Migraine (P7-12.010)