Acute Medication Use Research Articles

Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM)

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2–8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904.

Effect of the COVID-19 Pandemic on Headache in Pediatric Migraine Patients at a Single Tertiary Center

Purpose: The aim of this study was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on children and adolescents with migraine. Methods: This longitudinal cohort study enrolled children and adolescents with migraine from the Department of Pediatric Neurology at our hospital from January 2017 to June 2021. Self-reported data from individual headache diaries were used. The patients were questioned about their headache frequency and intensity, stress, physical activity, changes in mood and sleep, and their school and home lives during the COVID-19 pandemic. The Pediatric Migraine Disability Assessment (Ped-MIDAS) scoring system was applied to assess headache-related disability. Results: In total, 325 pediatric migraine patients (mean age 12.8±5.6 years, 62.5% female) were included in this study. The average monthly frequency of migraine headaches was 2.17±1.32 and 4.62±3.29 before and during the COVID-19 pandemic (P<0.001), respectively. The Ped-MIDAS score was obtained for 207 patients both before and during the pandemic, and the total score slightly increased from 13.8 to 14.7 points (P=0.295). Sixty patients (18.5%) showed significantly worsening migraine headaches. Younger age (P=0.017), mood deterioration (P<0.001), sleep problems (P<0.001), increased acute medication use (P=0.010), and larger changes in the Ped-MIDAS score (P=0.002) were significantly associated with worsening headache in the logistic regression analysis. Conclusion: Headache attacks in children and adolescents with migraine were more frequent during the COVID-19 pandemic than before it. Worsening headaches could be independently attributed to younger age, mood deterioration, and poor sleep during the COVID-19 pandemic.

Real-world efficacy of galcanezumab for the treatment of migraine in Korean patients

We aimed to provide real-world data on the effectiveness of an anti-calcitonin gene-related peptide monoclonal antibody administered for treating migraine in Korean patients. We prospectively recruited patients with migraine who received galcanezumab treatment at a single university hospital from June 2020 to April 2021. The treatment response was assessed after three consecutive monthly injections. A 50% responder rate was evaluated based on ≥50% reduction in the number of moderate/severe headache days. Overall, 87 patients were included in the analysis. Most patients were women (83.9%). They had a mean age of 41.7 ± 12.3 years (range 17-72). Sixty-five patients (74.7%) had chronic migraine, 35 patients (40.2%) had a history of medication-overuse headache, and 32 patients (36.8%) were previously unresponsive to or found intolerable five classes of preventive medication. After three months of treatment, mean changes in numbers of monthly headache days, moderate/severe headache days, crystal clear days, and days of acute medication use were -7.2 ± 8.43, -4.3 ± 9.76, 7.3 ± 8.50, and -4.1 ± 7.93, respectively. The 50% responder rates were 58.3%, 44.2%, and 40.6% for patients with unsuccessful previous use of 0-1, 2-4, and 5 preventive medication classes, respectively. Headache Impact Test-6 and Migraine Disability Assessment Test scores also decreased (-4.4 ± 8.09 and -32.9 ± 77.04, respectively). In our cohort, the effectiveness and safety of galcanezumab were comparable with those reported in clinical trials, whereas a higher response rate was observed in the difficult-to-treat patient subset than that reported in trials. We provide real-world evidence of galcanezumab treatment benefits in Asian patients with migraine.

Results of the gErman migraine PatIent Survey on medical Care and prOPhylactic treatment Experience (EPISCOPE)

Migraine affects about 12% of the worldwide population causing substantial personal and societal burden. Yet, migraine remains underdiagnosed and untreated. EPISCOPE was a web-based survey among a German migraine patient cohort to characterize the medical care and prophylactic treatment status aiming to identify unmet needs. Potential migraine patients were identified via an ID Migraine screener. Their socioeconomic background, medical care experience, acute medication use, as well as use and experience of migraine prophylaxis was assessed by a questionnaire. Data of 29,011 participants was collected. 21,504 participants were identified as migraine patients. Patients with a higher number of monthly migraine days experienced better medical care. However, even among chronic migraine patients, 54% were not consulting a physician, 30% did not feel well-informed about medication overuse and 48% had never tried prophylactic migraine treatment. Among patients receiving prophylactic migraine treatment, up to 33% were not satisfied with their prophylaxis due to insufficient efficacy. Taken together, EPISCOPE describes the largest German migraine patient cohort so far. The survey provides detailed and valuable insight into the current medical care and prophylactic treatment situation in a highly developed European country and identifies reasons why the medical care of migraine patients is still insufficient.

Acute Medication Use in Patients With Migraine Treated With Monoclonal Antibodies Acting on the CGRP Pathway: Results From a Multicenter Study and Proposal of a New Index.

IntroductionAssessing the impact of migraine preventive treatments on acute medication consumption is important in clinical evaluation. The number of acute medication intakes per each monthly migraine day (MMD) could provide insights on migraine burden and represent a new proxy of treatment effectiveness in clinical trials and real-life studies. We evaluated the effect of monoclonal antibodies acting on calcitonin gene-related peptide (CGRP) pathway on the consumption of migraine acute medication in real-life.MethodsIn two headache centers in Prague (CZ), we included and followed up to 6 months consecutive patients treated with MoAbs acting on CGRP (erenumab or fremanezumab). For each month of treatment, we reported monthly drug intake (MDI) in doses of any medication, migraine-specific (MS), and non-migraine-specific (non-MS) medications, and computed a ratio between MMDs and MDI, i.e., Migraine Medication Index (MMI) for MS and non-MS medications.ResultsWe included 90 patients (91.1% women) with a median age of 47 [interquartile range (IQR) 42–51] years; 81 (90.0%) treated with erenumab and 9 (10.0%) with fremanezumab. Median MMDs decreased from 11 (IQR 8–14) at baseline to 4 (IQR 2–5) at Month 3 (p < 0.001 vs. baseline) and 3 (IQR 2–6) at Month 6 (p < 0.001 vs. baseline). Median MDI decreased from 15 drug intakes (IQR 11–20) at baseline to four drug intakes (IQR 2–7) at Month 3 (p < 0.001) and four drug intakes (IQR 2–7) at Month 6 (p < 0.001).The corresponding MDIs for MS medications were 10 (IQR 6–14) at baseline, 3 (IQR 1–5, p < 0.001) at Month 3, and 2 (IQR 0–4, p < 0.001) at Month 6. Monthly drug intakes for non-MS medications were 4 (IQR 0–9) at baseline, 1 (IQR 0–3, p < 0.001) at Month 3 and at Month 6.Median MMI decreased from 1.32 (IQR 1.11–1.68) at baseline to 1.00 (IQR 1.00–1.50, p < 0.001) at Month 3 and 1.00 (IQR 1.00–1.34, p < 0.001) at Month 6.ConclusionsWe confirmed that MoAbs acting on CGRP pathway decrease acute migraine medication consumption. We proposed a new index that can be easily applied in clinical practice to quantify migraine burden and its response to acute medication. Our index could help optimizing migraine acute treatment in clinical practice.

Behavioural intervention in medication overuse headache: A concealed double-blind randomized controlled trial.

Background and purposeMedication overuse headache is a prevalent disorder, with a strong biobehavioural component. Hence, behavioural interventions might effectuate reduction of the overused medication. We assessed in a double‐blind manner the efficacy of a behavioural intervention during medication withdrawal therapy.MethodsIn this concealed, double‐blind, randomized controlled trial in medication overuse headache, conducted at the Leiden University Medical Centre, we compared the effect of maximal versus minimal behavioural intervention by a headache nurse during withdrawal therapy. Maximal intervention consisted of an intensive contact schedule, comprising education, motivational interviewing, and value‐based activity planning during 12 weeks of withdrawal therapy. Minimal intervention consisted of a short contact only. Patients were unaware of the existence of these treatment arms, as the trial was concealed in another trial investigating botulinum toxin A. Endpoints were successful withdrawal and monthly days of acute medication use after the withdrawal period.ResultsWe enrolled 179 patients (90 maximal, 89 minimal intervention). At Week 12, most patients achieved withdrawal in both groups (82/90 [93%] maximal intervention vs. 75/89 [86%] minimal intervention, odds ratio = 2.44, 95% confidence interval [CI] = 0.83–7.23, p = 0.107). At Week 24, patients in the maximal intervention group had fewer medication days (mean difference = −2.23, 95% CI = −3.76 to −0.70, p = 0.005). This difference receded over time. Change in monthly migraine days did not differ between groups (−6.75 vs. −6.22).ConclusionsThis trial suggests modest benefit of behavioural intervention by a headache nurse during withdrawal therapy for medication overuse headache, to reduce acute medication use during and shortly after intervention, but extension seems warranted for a prolonged effect

Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a\u2009\u2265\u200975% response to eptinezumab: subgroup pooled analysis of the PROMISE trials

BackgroundPROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide–targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50– < 75% MRR.MethodsPROMISE-1 and PROMISE-2 were phase 3, randomized, double-blind, placebo-controlled studies. This analysis included patients from both studies treated with eptinezumab 100 mg or 300 mg who experienced ≥ 75% and ≥ 50–< 75% MRR over Weeks 1–12 (wks1–12). In both studies, HRQoL was measured by the 36-item Short-Form Health Survey (SF-36) and acute medication usage. PROMISE-2 also included the 6-item Headache Impact Test (HIT-6), patient-identified most bothersome symptom (PI-MBS), and Patient Global Impression of Change (PGIC).ResultsIn PROMISE-1, a total of 115/443 (26.0%; 100 mg, n = 49, 300 mg, n = 66) and 120/443 (27.0%; 100 mg, n = 61, 300 mg, n = 59) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. In PROMISE-2, a total of 211/706 (30.0%; 100 mg, n = 95; 300 mg, n = 116) and 209/706 (29.6%; 100 mg, n = 110, 300 mg, n = 99) eptinezumab-treated patients achieved ≥ 75% and ≥ 50–< 75% MRR over wks1–12, respectively. EM and CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12 showed reduced use of acute headache medication and increased HRQoL to normative levels across SF-36 domains of bodily pain, social functioning, and physical functioning. In CM patients with ≥ 75% and ≥ 50–< 75% MRR over wks1–12, the mean change in HIT-6 total score with eptinezumab (pooled) was − 11.7 and − 7.6, respectively. “Very much” or “much” improvement responses were reported in 41.8% and 16.5% on PI-MBS and 36.2% and 20.0% on PGIC in ≥ 75% and ≥ 50–< 75% MRR, respectively.ConclusionEptinezumab treatment induced a ≥ 75% MRR over wks1–12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50–< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM.Trial registrationClinicalTrials.gov identifiers: NCT02559895 (PROMISE-1), NCT02974153 (PROMISE-2).

The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials

BackgroundMigraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efficacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies.MethodsMEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched before October 20, 2021 for any relevant literature. Eventually, three randomized clinical trials (RCTs) with 2,466 patients were included in our study.ResultsWe pooled 2,466 patients from 3 RCTs and primary outcome was mean monthly migraine days, the secondary endpoints were monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days, baseline to end of trials. It was found that atogepant (10 mg, 30 mg, 60 mg once a day) led to a significant reduction in monthly migraine days (P < 0.00001, P < 0.00001, P = 0.007), monthly headache days (P < 0.00001, P < 0.00001, P = 0.001), and monthly medication use days (P < 0.00001, P < 0.00001, P = 0.0001), and an increase in the proportion of people with ≥ 50% reduction in monthly migraine days (P = 0.0008, P = 0.02, P = 0.04) in comparison with placebo. Moreover, there were no significant differences (P > 0.05) in outcomes of adverse events between atogepant and placebo.ConclusionsAtogepant has shown good efficacy and safety in the prophylactic treatment of migraine, and further studies are expected.

Questionnaire-based survey on the prevalence of medication-overuse headache in Japanese one city-Itoigawa study.

ObjectiveThe medication-overuse headache (MOH) prevalence has not been investigated in a general Japanese population. We performed questionnaire-based survey and revealed MOH prevalence and its characteristics. We also performed clustering to obtain insight for MOH subgrouping.MethodsIn this cross-sectional study, the 15–64-year-old population was investigated in Itoigawa during their COVID-19 vaccination under the national policy. MOH was defined as ≥ 15 days/month plus self-report of use of pain medications ≥ 10 or 15 days/month in the last 3 months. Ward method and k-means + + were used to perform clustering MOH patients.ResultsAmong 5865 valid responses, MOH prevalence was 2.32%. MOH was common among females and the middle-aged. Combination-analgesic is the most overused as 50%. MOH had aggravation by routine physical activity, moderate or severe pain, and migraine-like, compared to non-MOH. The 136 MOH patients could be grouped into 3 clusters. Age and frequency of acute medication use were essential factors for clustering.ConclusionsThis is the first study of MOH prevalence in Japan. Most MOH characteristics were similar to previous reports worldwide. Public awareness of proper headache treatment knowledge is still needed. Clustering results may be important for subtype grouping from a social perspective apart from existing clinical subtypes.

Efficiency of erenumab in neurologist's real practice

To assess the effectiveness and safety of erenumab in real-life study. 33 patients with episodic and chronic migraine (30 females, mean age 39.2±9.2, 3 males, mean age - 49.3±7.6) received erenumab 70 mg for each 3 months. Patients achieved a 50% reduction in the number of days with headache, pain intensity, duration, the number of days of acute medication use, effect on daily activity (HIT-6), side effects, neuropsychological testing (Beck Depression scale, Spielberger-Khanin questionnaire, Hospital Depression and Anxiety Scale) were assessed. During the first month of therapy, a 50% decrease in headache days was observed in 48% of patients, during the second - in 53% of patients, during the third - in 51.5% of patients (p<0.001), a reduce in pain intensity, HIT-6 score, duration of migraine attack was observed (p<0.005). A decrease in situational anxiety was revealed (Spielberger-Khanin questionnaire, p=0.02), but not depression. There was a decrease in the consumption of triptans (p<0.0005) and other analgesics (p=0.0018). 1 patient noted transient constipation. The effectiveness and safety of erenumab in the outpatient practice is shown.

Efficacy and Safety of Repetitive Intravenous Sodium Valproate in Pediatric Patients With Refractory Chronic Headache Disorders: A Retrospective Review

BackgroundChronic headache disorders can cause substantial disability and be treatment refractory. Often, these patients are excluded from clinical trials with leaving little evidence to guide treatment. In adults, divalproex sodium is an effective preventive migraine treatment. MethodsAll pediatric patients admitted for first-time sodium valproate infusions to treat refractory, chronic migraine (CM), new daily persistent headache, or persistent headache attributed to head trauma from January 2017 to October 2020 were identified for review. Each patient underwent a standardized, 4-day protocol. A new preventive was started one week after discharge. Data on headache frequency, severity, and acute medication use were collected through preadmission and postadmission clinic notes. Safety and tolerability were evaluated. Results were evaluated using descriptive statistics and compared with paired t-tests. ResultsForty-five patients were identified for review. Patients with CM had a median of 7 previous preventive trials, and 85% had previously received alternative intravenous treatment for headache. Baseline headache pain significant decreased from 6.9/10 to 5.4/10 by 7-week postadmission follow up, (95% confidence interval = −0.7 to −2.4), P < 0.001. Use of medications for acute headache treatment decreased significantly from 2.1 days/week to 1.5 days/week, (95% confidence interval = −0.3 to −1), P < 0.001. Baseline headache frequency did not significantly change. At postadmission follow-up, 26 of 39 (67%) patients saw improvements in headache frequency, headache intensity, and/or acute pain medication usage. There were no serious adverse events. ConclusionsRepetitive sodium valproate infusions were well tolerated and significantly reduced baseline headache intensity and acute medication usage in pediatric patients with refractory, chronic headache disorders.

Gender Differences in 3-Month Outcomes of Erenumab Treatment-Study on Efficacy and Safety of Treatment With Erenumab in Men.

Objective: We reported gender-specific data on the efficacy and safety of erenumab, a monoclonal antibody antagonizing the calcitonin gene-related peptide (CGRP) receptor.Methods: Our pooled patient-level analysis of real-world data included patients treated with erenumab and followed up for 12 weeks. We considered the following outcomes at weeks 9–12 of treatment compared with baseline: 0–29%, 30–49%, 50–75%, and ≥75% responder rates, according to the decrease in monthly headache days (MHDs), rate of treatment stopping, change in MHDs, monthly migraine days (MMDs), monthly days of acute medication and triptan use, and Headache Impact Test-6 (HIT-6) score from baseline to weeks 9–12. Outcomes were compared between men and women by the chi-squared test or t-test, as appropriate. An analysis of covariance (ANCOVA) was performed to identify factors influencing the efficacy outcomes.Results: We included 1,410 patients from 16 centers, of which 256 (18.2%) were men. Men were older than women and had a lower number of MHDs at baseline. At weeks 9–12, compared with baseline, 46 (18.0%) men had a ≥75% response, 75 (29.3%) had a 50–74% response, 35 (13.7%) had a 30–49% response, and 86 (33.6%) had a 0–29% response, while 14 (5.5%) stopped the treatment. The corresponding numbers for women were 220 (19.1%), 314 (27.2%), 139 (12.0%), 402 (34.8%), and 79 (6.8%). No gender difference was found in any of the outcomes. The ANCOVA showed that gender did not influence the efficacy of outcomes.Conclusion: We found that erenumab is equally safe and effective in men compared with women after 12 weeks.

Comprehensive approach for the treatment of medication-overuse headache

Background: Medication-overuse headache (MOH) is defined by the International Classification of Headache Disorders as a headache in patients with a pre-existing primary headache disorder that occurs on 15 or more days per month for more than 3 months. It is caused by overuse of medication for acute or symptomatic headache treatment. Regular and frequent use of acute or symptomatic medications can worsen headaches and lead to chronic headache or MOH. MOH is a burdensome medical condition that is difficult to treat, and the frequent recurrence of headaches may result in disability in individuals and impair socioeconomic outcomes.Current Concepts: Awareness of MOH and the education of patients, the general population, and healthcare providers are important for the first step of treatment. Scientific research regarding the treatment of MOH has been published in the past few years.Discussion and Conclusion: Physicians should educate and counsel patients to stop or at least reduce the intake of acute or symptomatic medications that can be discontinued abruptly or tapered slowly. During the period after the discontinuation of the overused medications, some withdrawal symptoms including headache might be manageable with bridging therapy. Evidence-based preventive therapies including anticonvulsants (topiramate and divalproex sodium), botulinum toxin A, and medications acting by antagonism of the calcitonin generelated peptide pathway might be helpful in patients with MOH for both avoiding the overused medication and preventing the relapse of overuse. A comprehensive and multidisciplinary approach may improve the outcomes of patients with MOH.

Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study

BackgroundMigraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2∆a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18–45 years and > 45 years) and sex.MethodsIn the FOCUS study, eligible participants were randomized (1:1:1) to 12 weeks of double-blind treatment with quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. In this post hoc analysis, we evaluated changes from baseline in monthly migraine days (primary endpoint of FOCUS) and other secondary and exploratory efficacy outcomes in prespecified age (18–45 and > 45 years) and sex subgroups.ResultsThe modified intention-to-treat population (received ≥ 1 dose of study drug and had ≥ 10 days of postbaseline efficacy assessments for the primary endpoint) totaled 837 participants (18–45 years, n = 373; > 45 years, n = 464; male, n = 138; female, n = 699). Consistent reductions in monthly average number of migraine days during 12 weeks were observed, regardless of age (18–45 years: quarterly fremanezumab, − 4.1 days; monthly fremanezumab, − 4.7 days; placebo, − 0.9 days; P < 0.001; > 45 years: quarterly fremanezumab, − 3.6 days; monthly fremanezumab, − 3.7 days; placebo, − 0.3 days; P < 0.001) and sex (male: quarterly fremanezumab, − 4.1 days; monthly fremanezumab, − 4.6 days; placebo, − 0.3 days; P < 0.001; female: quarterly fremanezumab, − 3.6 days; monthly fremanezumab, − 3.9 days; placebo, − 0.6 days; P < 0.001). Fremanezumab also reduced monthly headache days of at least moderate severity, monthly days of acute medication use, and improved Migraine Disability Assessment scores across subgroups.ConclusionsThese results demonstrate the efficacy of fremanezumab in patients with difficult-to-treat migraine for reducing migraine and headache days, acute medication use, and disability, regardless of age or sex.Trial registrationClinicalTrials.gov Identifier NCT03308968 (FOCUS), registered October 13, 2017.

The burden of medication overuse headache and patterns of switching and discontinuation among triptan users: a systematic literature review

BackgroundA synthesis of real-world discontinuation and switching patterns among triptan users and rates of acute medication use among patients with medication overuse headache (MOH) is needed to better understand the burden among patients with migraine. The study objectives were to: (1) synthesize rates of switching and discontinuation from triptans; (2) characterize acute medication use among patients with MOH; and (3) describe the associated burden.MethodsA systematic literature review was conducted, under the Preferred Reporting Items for Systematic Review guidelines, using MEDLINE/EMBASE from database inception to July 2019. The search strategy targeted studies of adults with migraine, and included terms related to migraine and its treatment. Continuous variables were summarized using means, standard deviations, and ranges. Dichotomous and categorical variables were summarized using the number and proportion of individuals.ResultsTwenty studies were included; seven describing patterns of switching and discontinuation among triptan users, and 13 characterizing triptan overuse among patients with MOH. High rates of switching to non-specific acute medications and low two-year retention rates were reported; among US samples switching to opioids at the first refill (18.2%) or after 1-year (15.5%) was frequent. Compared to persistent use of triptans, switchers experienced greater headache related impact and either no improvement or increased headache-related disability. Rates of medication overuse by agent among patients with MOH varied greatly across the included studies, and only one study described factors associated with the risk of MOH (e.g. duration of medication overuse). Medication agent, increased headache frequency (p = .008), and increased disability (p = .045) were associated with unsuccessful withdrawal; patients overusing triptans were more successful at withdrawal than those overusing opioids or combination analgesics (P < .0001).ConclusionsThe evidence summarized here highlights that rates of WCS are low and many patients turn to other acute medication at their first refill. Patients may experience no improvement in disability when switching from one triptan agent to another, or experience increasing disability and/or increasing migraine frequency when turning to traditional acute treatment for migraine. Variability in health care settings, patient severity, and study design contributed to heterogeneity across the synthesis.

P.033 Eptinezumab reduced acute medication use in patients with chronic migraine and medication-overuse headache: subgroup analysis of Promise-2

Background: Eptinezumab is a preventive migraine treatment approved in the US. We evaluated the impact of eptinezumab on acute headache medication (AHM) use in patients diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) in PROMISE-2. Methods: PROMISE-2 randomized patients with CM to eptinezumab 100mg, 300mg, or placebo for 2 intravenous doses administered every 12 weeks. Trained investigators diagnosed MOH at screening using 3-month medication history and ICHD-3b criteria. Endpoints included days/month of any AHM use (days of ≥1 medication class), total AHM use (summed days for each medication class), and triptan use over Weeks 1-12 and 13-24. AHM classes included triptan, ergot, opioid, simple analgesic, and combination analgesic. Results: Of 1072 PROMISE-2 patients, 431 (40.2%) were diagnosed with MOH (100mg, n=139; 300mg, n=147; placebo, n=145). During the 28-day baseline period, mean days of any AHM was ~16.4, total AHM was ~20.4, and triptan was ~8.9 across treatment arms. Over Weeks 1-12, mean days/month of any AHM was 8.8 (100mg), 9.9 (300mg), and 11.8 (placebo); total AHM was 10.8, 12.2, and 14.8; triptan was 4.3, 4.4, and 6.4. Similar or lower rates were observed over Weeks 13-24. Conclusions: In patients diagnosed with both CM and MOH, eptinezumab treatment reduced AHM use.

Long-Term Safety and Tolerability of Fremanezumab for Migraine Preventive Treatment in Japanese Outpatients: A Multicenter, Randomized, Open-Label Study.

IntroductionEarly discontinuation and poor adherence are common limitations of conventional preventive migraine medications that limit their long-term efficacy. Therefore, a migraine preventive medication with favorable long-term safety is warranted.ObjectiveThis study aimed to evaluate the long-term safety and tolerability of fremanezumab for the preventive treatment of chronic or episodic migraine in Japanese patients.MethodsIn this 52-week, randomized, open-label, parallel-group study, fremanezumab monthly or quarterly was administered in newly enrolled Japanese patients with chronic migraine or episodic migraine. Safety was assessed by monitoring of treatment-emergent adverse events, including injection-site reactions, laboratory and vital sign assessments. Newly enrolled patients and rollover patients from previous phase IIb/III trials who did not receive fremanezumab in this study were included in the immunogenicity testing cohort (n = 587). Efficacy outcomes included changes from baseline in the average monthly migraine days and headache days of at least moderate severity. Other efficacy outcomes included changes in disability scores.ResultsA total of 50 patients were enrolled with chronic migraine (monthly, n = 17; quarterly, n = 17) or episodic migraine (monthly, n = 8; quarterly, n = 8). The most commonly reported treatment-emergent adverse events were nasopharyngitis (64.0%) and injection-site reactions (erythema, 24.0%; induration, 10.0%; pain, 8.0%; pruritus, 6.0%). The discontinuation rate was low (4.0% from adverse events, 2.0% from a lack of efficacy) and no deaths were reported. The incidence of anti-drug antibody development was low (2.4%). Fremanezumab reduced monthly migraine days and headache days of at least moderate severity from 1 month after initial administration, and this effect was maintained with no worsening throughout 12 months. Fremanezumab also led to sustained reductions in any acute headache medication use and headache-related disability at 12 months.ConclusionsFremanezumab administered monthly and quarterly was well tolerated in patients with chronic migraine and episodic migraine and led to sustained improvements in monthly migraine days and headache days of at least moderate severity throughout 12 months.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT03303105.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01119-2.

Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: A multi-center retrospective cohort study.

BackgroundSwitching between antibody classes might be a treatment option in migraine patients who have not responded to one class of a CGRP-(receptor) monoclonal antibody (mAb), but there are no efficacy data so far. In this real-world analysis, we assessed the treatment response to a CGRP-mAb in patients that have previously failed the CGRP-receptor-mAb erenumab.MethodsWe analyzed retrospective headache diary data of 78 patients with migraine who switched between CGRP-mAbs classes at four German headache centers either due to lack of efficacy or intolerable side effects. Among these, we identified 25 patients who did not respond to erenumab after three treatment cycles (defined as <30% reduction of monthly headache days) and had complete headache documentation at least one month before and during both treatments. We assessed the ≥30% responder rate at month three after switching from erenumab to a CGRP-mAb (galcanezumab or fremanezumab) (primary endpoint). Secondary endpoints included ≥50% responder rate, monthly headache days, and monthly days with acute medication use. In an exploratory subgroup analysis patients were stratified for daily and non-daily headache.ResultsThe switch from erenumab to a CGRP-mAb led to a ≥30% response in one-third (32%) of the patients after three treatment cycles. A ≥50% response was achieved in 12% of the patients. Monthly headache days were reduced in month three compared to baseline (20.8 ± 7.1 to 17.8 ± 9.1; p = 0.009). Stratified analysis revealed that no patient with daily headache (n = 9) responded to the treatment switch, while a 30% response was achieved by 50% of patients with non-daily headache (n = 16).ConclusionOur findings demonstrate that a relevant proportion of erenumab non-responders might benefit from a treatment switch to a CGRP-mAb. Switching seems to be a promising treatment option especially in migraine patients with non-daily headache.

Reversion from medication overuse with fremanezumab treatment in patients with inadequate response to multiple migraine preventive medication classes

Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), has demonstrated efficacy for migraine prevention in patients with documented inadequate response to 2–4 prior preventive medication classes in the phase 3b FOCUS study. The aim of this subgroup analysis was to evaluate reductions in acute medication use in patients treated with fremanezumab with baseline medication overuse (MO; any acute medication ≥15 days/month or triptans, ergots, or combination medications ≥10 days/month).

Migraine evolution after the cessation of CGRP(-receptor) antibody prophylaxis: a prospective, longitudinal cohort study

BackgroundNational and international guidelines recommend stopping migraine prophylaxis with CGRP(-receptor) monoclonal antibodies after 6–12 months of successful therapy. In this study, we aimed to analyze the course of migraine for four months after the cessation of CGRP(-receptor) antibodies use.MethodsThis longitudinal cohort study included patients with migraine who received a CGRP-(receptor) antibody for ≥8 months before treatment cessation. We analyzed headache data in the four-week period prior to mAb treatment initiation (baseline), in the month before the last mAb injection, in weeks 5–8 and 13–16 after last treatment. Primary endpoint of the study was the change of monthly migraine days from the month before last treatment to weeks 13–16. Secondary endpoints were changes in monthly headache days and monthly days with acute medication use.ResultsA total of 62 patients equally distributed between prophylaxis with the CGRP-receptor antibody erenumab and the CGRP antibodies galcanezumab or fremanezumab participated in the study. Patients reported 8.2 ± 6.6 monthly migraine days in the month before last treatment. Monthly migraine days gradually increased to 10.3 ± 6.8 in weeks 5–8 (p = 0.001) and to 12.5 ± 6.6 in weeks 13–16 (p < 0.001) after drug cessation. Monthly migraine days in weeks 13–16 were not different from baseline values (−0.8 ± 5.4; p > 0.999). Monthly headache days and monthly days with acute medication use showed a similar pattern.ConclusionsThe cessation of CGRP(-receptor) antibodies migraine prophylaxis was associated with a significant increase of migraine frequency and acute medication intake over time.