Monthly Headache Research Articles

Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials.

IntroductionGalcanezumab, a humanized monoclonal antibody that binds to calcitonin gene-related peptide, is approved for the preventive treatment of migraine in adults. It is self-administered once monthly as a subcutaneous injection. This paper describes the time course of effect of galcanezumab in patients with episodic and chronic migraine.MethodsData were based on three double-blind, placebo-controlled, phase 3 studies. Patients (1773 episodic and 1113 chronic) were randomized (2:1:1) to monthly doses of placebo, galcanezumab 120 mg with a 240 mg loading dose, or galcanezumab 240 mg (January 2016–March 2017). Onset of effect was determined using a sequential analysis approach based on earliest time point at which galcanezumab achieved and subsequently maintained statistical superiority to placebo. Maintenance of effect was a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of at least 50% response at the individual patient level. Cessation of effect was determined during a 4-month post-treatment period on the basis of change from baseline in monthly migraine headache days.ResultsGalcanezumab led to a lower percentage of patients who had a migraine headache on the first day after injection, provided maintenance of effect throughout the duration of the double-blind treatment period, and gradually lost effect without signs of rebound headache throughout the post-treatment period in most patients with episodic and chronic migraine.ConclusionGalcanezumab is a novel preventive therapeutic option for adult patients with migraine that has early onset of action, maintenance of effect, and gradual reduction of effect upon treatment cessation.Trial RegistrationClinicalTrials.gov: NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01632-x.

Prevalence and characteristics of cutaneous allodynia in probable migraine

Cutaneous allodynia (CA) is a pain in response to non-nociceptive stimulation and a marker of central sensitisation. Probable migraine (PM) is a migraine subtype that fulfils all but one criterion of migraine. Headache intensity and the disability of individuals with PM are similar or lower than individuals with migraine. This study compared CA prevalence and characteristics of PM and migraine using a nationally representative sample in Korea. The Allodynia Symptom Checklist-12 (ASC-12) was used to assess CA (ASC-12 score ≥ 3). PM and migraine prevalence were 11.6% and 5.0%, respectively. CA prevalence did not significantly differ between PM and migraine (14.5% vs. 16.0%, p = 0.701). Participants with PM with CA reported a higher monthly headache frequency (3.3 ± 4.3 vs. 1.8 ± 3.6, p = 0.044), more severe headache intensity (Visuals Analogue Scale, 6.0 [4.0–7.0] vs. 5.0 [3.0–6.0], p = 0.002), and higher impact of headache (Headache Impact Test-6, 56.3 ± 7.2 vs. 48.3 ± 8.0, p < 0.001) than those without CA. Multiple regression analyses revealed that headache frequency and intensity, anxiety, and depression were significant factors for CA in participants with PM. In conclusion, CA prevalence among participants with PM and migraine were comparable. Anxiety, depression, and headache frequency and intensity were significant factors for CA in participants with PM.

Topiramate, acupuncture, and BoNT-A for chronic migraine: a network meta-analysis.

Botulinum neurotoxin A (BoNT-A) was the primary choice for preventive treatment of chronic migraine. Topiramate and acupuncture showed promising effect for chronic migraine, but their effectiveness relative to BoNT-A was rarely studied. We aimed to perform a network meta-analysis to compare the effectiveness and acceptability between topiramate, acupuncture, and BoNT-A. We searched OVID Medline, Embase, the Cochrane register of controlled trials (CENTRAL), the Chinese Clinical Trial Register, and clinicaltrials.gov for randomized controlled trials (RCTs) that compared topiramate, acupuncture, and BoNT-A with any of them or placebo in the preventive treatment of chronic migraine. A network meta-analysis was performed by using a frequentist approach and a random-effects model. The primary outcomes were reduction in monthly headache days and monthly migraine days at week 12. Acceptability was defined as the number of dropouts owing to adverse events. We included 15 RCTs (n=2545). Eleven RCTs were at low risk of bias. The network meta-analyses (n=2061) showed that acupuncture (2061 participants; standardized mean difference [SMD] -1.61, 95% CI: -2.35 to -0.87) and topiramate (582 participants; SMD -0.4, 95% CI: -0.75 to -0.04) ranked the most effective in the reduction of monthly headache days and migraine days, respectively; but they were not significantly superior over BoNT-A. Topiramate caused the most treatment-related adverse events and the highest rate of dropouts owing to adverse events. Topiramate and acupuncture were not superior over BoNT-A; BoNT-A was still the primary preventive treatment of chronic migraine. Large-scale RCTs with direct comparison of these three treatments are warranted to verified the findings.

Redefining Expectations for Migraine Prevention

With the advent of new preventive migraine treatments, such as calcitonin gene-related peptide inhibitor monoclonal antibodies, there is a need to ensure realistic treatment expectations, and to carefully consider therapeutic options. Current treatment guidelines suggest that reductions in mean monthly headache days of ≥50% from baseline should be considered evidence of treatment efficacy, although in some patients, benefits can be seen at lower thresholds. However, patients may expect greater reductions in migraine attacks, so setting realistic expectations is important for treatment success. As treatment side effects and a lack of efficacy are the main reasons for treatment discontinuation, possible side effects should be discussed, and the individual goals of patients considered. Current American Headache Society guidelines suggest candidacy for preventive migraine treatment is primarily based on the frequency of attacks in the USA, with treatment recommended for patients who have ≥4 migraine days per month. However, even fewer than 4 monthly headache days per month can have a severe impact on overall health-related quality of life in addition to impairment during individual episodes. Finally, the use of acute therapy should be carefully monitored and considered when treatment decisions are being made, to ensure optimization of use, and to avoid overuse and progression to chronic migraine. These considerations indicate that patient needs are multifaceted and that management decisions need to be crafted on a case-by-case basis.

Medication overuse headache: The effectivity of iv lidocaine - magnesium.

The detoxification process in medication overuse headache is the most difficult process for the patient. We aimed to investigate the effectiveness of the combination of low dose IV lidocaine and magnesium (100 mg lidocaine and 1.25 mg magnesium) in patients with medication overuse headache during the detoxification process. A total of 30 patients were included in the study; 15 received 24 hours of IV hydration, 15 received 1-hour lidocaine-magnesium infusion at the onset of pain in addition to the 24 hours of IV hydration. Headache severity (numeric rating scale, NRS), attack durations, onset of headache, monthly analgesic/triptan intakes, numbers of monthly headache days data were documented. We evaluated the severity of headache before and after daily treatment of two groups for one week. When both groups were compared, there was no significant difference in the pre-treatment NRS values, whe-reas, in the group receiving IV lidocaine-magnesium combination, there was a statistically significant decrease in the post-treatment NRS values in the first five days (p <0.05). An 1-hour combined infusion of lidocaine-magnesium may be considered as an alternative option for the patient to have a more quality detoxification process during the hospital stay, so that in parallel to the reduction in the use of multiple treatments (such as neuroleptics, benzodiazepines, antiemetics and opioids) and duration length of stay, the economic costs can also be reduced. The administration of combination will bring fewer side effects compared to their administration separately.

Outcomes of Occipital Nerve Stimulation for Craniofacial Pain Syndromes.

Occipital nerve regional stimulation (ONS) is reported to improve pain in several studies. We examined long-term pain and functional outcomes of ONS in an open-label prospective study. Patients with medically refractory and disabling craniofacial pain were prospectively selected for ONS. Primary outcome was a change in mean daily pain intensity on the numeric pain rating scale (NPRS) at 6 months. Secondary outcomes included changes in NPRS, Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Pain Disability Index (PDI), Center for Epidemiologic Studies Depression Scale - Revised (CESD-R), and Short Form-36 version 2 (SF36) at last follow-up. Thirteen patients (mean age 49.7 ± 8.4) diagnosed with occipital neuralgia (6), hemicrania continua (2), persistent idiopathic facial pain (2), post-traumatic facial pain (1), cluster headache (1), and chronic migraine (1) were enrolled. Mean NPRS improved by 2.1 ± 2.1 at 6 months and 2.1 ± 1.9 at last follow-up (23.5 ± 18.1 months). HIT-6 decreased by 8.7 ± 8.8, MIDAS decreased by 61.3 ± 71.6, and PDI decreased by 17.9 ± 18. SF36 physical functioning, bodily pain, and social functioning improved by 16.4 ± 19.6, 18.0 ± 31.6, and 26.1 ± 37.3, respectively. Moderate to severe headache days (defined as ≥50% of baseline mean NPRS) were reduced by 8.9 ± 10.2 days per month with ONS. ONS reduced the long-term NPRS and moderate-severe monthly headache days by 30% and improved functional outcomes and quality of life. A prospective registry for ONS would be helpful in accumulating a larger cohort with longer follow-up in order to improve the use of ONS.

Interrelations between migraine-like headache and persistent post-traumatic headache attributed to mild traumatic brain injury: a prospective diary study

BackgroundPersistent post-traumatic headache (PTH) is a common sequela of mild traumatic brain injury (TBI) and retrospective assessments have found a migraine-like phenotype to be very frequent. This has raised a discussion of shared underlying mechanisms and whether persistent PTH is simply trauma-triggered migraine.MethodsA 28-day prospective diary study with daily entries and acquisition of data on headache characteristics, associated symptoms, and acute medication use. A total of 64 patients with persistent PTH were enrolled from April 2019 to August 2019. Outcomes were the proportion of monthly headache days of any intensity that met the criteria for a migraine-like day or TTH-like day, as well as the corresponding figures for monthly headache days of moderate to severe intensity. Headache phenotypes were initially assigned based on diagnostic evaluation by semi-structured interview, whilst final headache phenotypes were assigned by diary review.ResultsAfter diary review, we found that monthly headache days were exclusively migraine-like in 24 of 64 patients (38%) and exclusively TTH-like days in 8 of 64 patients (13%). Considering only monthly headache days of moderate to severe intensity, the corresponding figures were 35 of 64 patients (55%) for migraine-like days and 8 of 64 patients (13%) for TTH-like days. The following headache phenotypes were assigned based on diary review: chronic migraine-like (n = 47, 73%), combined episodic migraine-like and chronic TTH-like (n = 9, 13%), and ‘pure’ chronic TTH-like (n = 8, 13%).ConclusionsA migraine-like phenotype is common in patients most adversely affected by persistent PTH, although some patients did have a pure chronic TTH-like phenotype. At minimum, these findings suggest that persistent PTH is – at least in some – not ‘trauma-triggered migraine’.

Erenumab and OnabotulinumtoxinA Combination Therapy for the Prevention of Intractable Chronic Migraine without Aura: A Retrospective Analysis

Erenumab is a monoclonal antibody that mediates calcitonin-gene-related peptide (CGRP), a pro-inflammatory polypeptide implicated in migraine pathology, by targeting its receptor. To date, no clinical trial has evaluated combination therapy with both erenumab and onabotulinumtoxinA therapy for the treatment of chronic migraine. We conducted a retrospective chart review of 78 patients to investigate if the addition of erenumab to patients with chronic migraines receiving onabotulinumtoxinA had a decrease in their total monthly headache days (MHDs) and monthly migraine days (MMD). At baseline, while on onabotulinumtoxinA, mean MHDs were 22.5 ± 8.7 and mean MMDs were 15.8 ± 8.3, and 65 patients (83.3%) failed at least three preventative therapies. Our results demonstrated a significant reduction in MHDs and MMDs at 30- (-6.8 MHDs; p < 0.001, −7.0 MMDs; p < 0.001), 60- (-7.2 MHDs; p < 0.001, −6.7 MMDs; p < 0.001), and 90 days (-8.1 MHDs; p < 0.001, −7.4 MMDs; p < 0.001). Thus, the results of this study suggest favorable outcomes with the addition of erenumab to patients who were still suffering while receiving onabotulinumtoxinA therapy. Additional investigation is needed to determine if erenumab in combination with onabotulinumtoxinA has an enhanced effect on the modulation of CGRP release from peripheral unmyelinated C fibers while also blocking CGRP receptors in the myelinated A-delta fibers.

Demographics, Headache Features, and Comorbidity Profiles in Relation to Headache Frequency in People With Migraine: Results of the American Migraine Prevalence and Prevention (AMPP) Study.

Migraine is typically divided into 2 headache frequency denominated categories, episodic migraine (EM) and chronic migraine (CM). Characterizing more narrow headache day frequency groups may be of value for better understanding the broad range of migraine experience and making treatment decisions. To characterize the impact and burden of migraine in 4 monthly headache day (MHD) categories. Respondents to the American Migraine Prevalence and Prevention Study 2005 survey who met criteria for migraine were categorized into low frequency episodic migraine (LFEM) 0-3, moderate frequency episodic migraine (MFEM) 4-7, high frequency episodic migraine (HFEM) 8-14, and CM with ≥15 headache days per month. Data including sociodemographics, headache features and symptomology, comorbidities, cutaneous allodynia, and severe migraine-related disability were compared among groups. We combined the low- and medium-frequency EM groups (L/MFEM) and compared them with the HFEM group in 1 set of models and compared the HFEM and CM groups in a second set of models. Binary logistic regression, linear regression, and ordered logistic regression were used depending upon the variable type and adjusted for sociodemographics. Among 11,603 eligible respondents with migraine, 67.7% (7860/11,603) were categorized with LFEM, 17.7% (2051/11,603) with MFEM, 7.8% (898/11,603) with HFEM, and 6.8% (794/11,603) with CM. The mean age was 46 (SD 13.7), 80.2% (9301/11,603) were female, and 90.0% (10,187/11,323) were White, 6.9% were Black (784/11,323), and 3.1% (352/11,323) were identified as Other race(s). Individuals with HFEM differed from L/MFEM on a wide range of sociodemographic variables in the categories of headache features, disability, and comorbidities while few differences were found when modeling HFEM vs CM. In comparison with L/MFEM and HFEM, the HFEM group was more likely to have severe disability (P<.001 OR=1.74 [1.42, 2.15]), chronic pain (P≤.007 OR=1.35 [1.09, 1.69]), arthritis (P=.001 OR=1.44 [1.15, 1.80]), high cholesterol (P=.005, OR=1.37 [1.10, 1.70]), ulcers (P=.016, OR=1.44 [1.07, 1.93]), and depression (Patient Health Questionnaire [PHQ-9]) (P<.001 OR=1.50 [1.22, 1.84]). While rates of migraine symptoms, headache impact and disability, and comorbidities generally increased with increases in MHD frequency, respondents with HFEM and CM were remarkably similar on a broad range of variables including sociodemographics, disability/impact, and comorbidities. There were many more significant differences between the HFEM and L/MFEM groups on the same variables. Future work should use empirical strategies to identify naturally occurring groups and possibly reconsider the boundary between CM and HFEM.

Benefits Beyond Headache Days With OnabotulinumtoxinA Treatment: A Pooled PREEMPT Analysis.

IntroductionThe double-blind, phase 3 PREEMPT trials demonstrated the efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis evaluated the effect of onabotulinumtoxinA on clinically meaningful changes in headache severity, headache-related impact, and quality of life.MethodsPooled, 24-week data were used to determine percentages of patients meeting responder criteria for the change in headache days (≥ 50% reduction in headache-day frequency), Headache Impact Test (HIT-6; ≥ 5-point improvement), MSQ Role Function-Restrictive (MSQ-RFR; ≥ 10.9-point improvement), and Average Daily Headache Severity (ADHS; ≥ 1-point improvement on a 4-point ordinal scale [0 = no pain, 3 = severe pain]).ResultsIn the pooled analysis population (N = 1384; onabotulinumtoxinA, n = 688; placebo, n = 696), significantly more patients treated with onabotulinumtoxinA compared with placebo were responders on HIT-6 (40.8 vs. 25.3%), MSQ-RFR (59.0 vs. 40.2%), and ADHS (35.5 vs. 22.4%) measures, and achieved traditional ≥ 50% reduction in headache days (44.8 vs. 34.2%; all P < 0.001). At least one responder criterion was met by 72.1% and 56.6% of onabotulinumtoxinA- and placebo-treated patients, respectively; all four were met by 20.4% and 8.6%, respectively (P < 0.001). Linear regression analysis showed that approximately 20% of the variance in HIT-6 and MSQ-RFR improvement was explained by improvement in headache days.ConclusionsTreatment with onabotulinumtoxinA for 24 weeks was associated with clinically meaningful benefits beyond reduction in headache days; including reductions in headache severity and headache-related impact, and improved quality of life. While 45% of patients met responder criteria for monthly headache days, over 70% had clinically meaningful improvements on at least one outcome measure.Trial RegistrationClinicalTrials.gov identifier, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2)

Erenumab in Chronic Migraine: An Australian Experience.

To determine the effectiveness and safety of erenumab in patients with chronic migraine in the real-world setting of 3 headache centers in Australia. Patients with migraine were prescribed erenumab (70 or 140mg) in the setting of either a product familiarization program or paid access to the medication in 3 headache centers in Australia. We obtained baseline and monthly prospective data on monthly headache days, monthly migraine days, monthly triptan use days, monthly codeine use days, Headache Impact Test-6 scores, and adverse reactions. In this paper, we present our data at 3 and 6months in our subgroup of patients with chronic migraine with and without medication overuse. A total of 170 patients with chronic migraine were prescribed erenumab in the 3 headache centers. At 3months, 100/170 (58.8%) had 50% or greater reduction in monthly migraine days. At 6months, 79/170 (46.5%) had 50% or greater reduction in monthly migraine days. At 6months, there was a mean reduction in monthly headache days of 9.2days, a mean reduction in monthly migraine days of 10.2days. There were few adverse events reported. This is the first report from 3 Australian headache centers about erenumab in the real world. Our analysis has supported erenumab as an effective and well-tolerated migraine preventative therapy for patients with chronic migraine who have failed many preventative therapies.

Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial

Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories. CONQUER was a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial done at 64 sites (hospitals, clinics, or research centres) in 12 countries (Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, the Netherlands, South Korea, Spain, the UK, and the USA). Patients were 18-75 years of age, with episodic or chronic migraine, with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug categories in the past 10 years owing to lack of efficacy or tolerability, or both. Patients were randomised 1:1 to receive subcutaneous placebo or galcanezumab 120 mg per month (with a 240 mg loading dose administered as two 120 mg injections) for 3 months. For masking purposes, patients receiving placebo also received two injections during the first dosing visit. Randomisation was done by a computer-generated random sequence by means of an interactive web-response system stratified by country and migraine frequency (low frequency episodic migraine, four to fewer than eight migraine headache days per month; high frequency episodic migraine, eight to 14 migraine headache days per month and fewer than 15 headache days per month; chronic migraine, at least eight migraine headache days per month and at least 15 headache days per month). The primary endpoint was the overall mean change from baseline in number of monthly migraine headache days during the 3-month treatment period in all patients who were randomly assigned and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03559257, and is now completed. Between Sept 10, 2018, and March 21, 2019, 462 participants with episodic (269 [58%]) or chronic (193 [42%]) migraine were randomly assigned and received at least one injection with placebo (n=230) or galcanezumab (n=232). Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo across months 1-3. The galcanezumab group had on average 4·1 fewer monthly migraine headache days compared with baseline (13·4), while the placebo group had on average 1·0 fewer than at baseline (13·0; between-group difference -3·1 [95% CI -3·9 to -2·3]; p<0·0001; effect size=0·72). Types and number of treatment-emergent adverse events were similar between galcanezumab and placebo. Treatment-emergent adverse events were reported in 122 (53%) of 230 patients in the placebo group and 119 (51%) of 232 patients in the galcanezumab group. There were four serious adverse events during the study, two (1%) reported in the placebo group and two (1%) reported in the galcanezumab group. Galcanezumab was superior to placebo in the preventive treatment of migraine and was safe and well tolerated in patients for whom multiple previous standard-of-care preventive treatments had failed. Galcanezumab might represent an important treatment option for patients who have not benefited from or tolerated previous standard-of-care treatments. Eli Lilly.

Real-World Patient Experience With Erenumab for the Preventive Treatment of Migraine.

Erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, has been well tolerated with good efficacy for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 clinical trials. Limited post-market observations are available to validate these findings in a real-world tertiary headache clinic population with complex comorbidities and refractory migraine. The goal of this study is to demonstrate the real-world performance of erenumab among patients in a tertiary care headache clinic by describing patient selection, experience, and clinical characteristics after 6months of erenumab therapy. A retrospective, exploratory, observational study was conducted on patients receiving at least 1 erenumab injection (70 or 140mg). Baseline data obtained by chart review and telephone calls were compared to 6-month follow-up telephone calls. The primary outcome was the reduction in self-reported headache days per month at baseline compared to 6months for those with complete 6-month data. The significance level was set at P<.05. Secondary analyses explored the distribution of headache severity, responder rates, Migraine Disability Assessment scores, adverse effects, ineffective preventives, comorbidities, wearing-off, and discontinuation. Of the 101 patients who consented to participate, 89.1% (90/101) were women, and the mean age of all patients was 49years (range, 19-80 years). At baseline, 94.1% (95/101) of patients had chronic migraine, 5.0% (5/101) had episodic migraine, and 18.8% (19/101) had medication overuse headache. The mean (SD) number of baseline headache and migraine days per month for the entire cohort were 24.3 (8.2) and 18.2 (9.3) days, respectively. Participants had numerous comorbidities and had tried a mean of 11.2 unique oral medications and 4.8 unique medication categories before receiving erenumab, including 83.2% (84/101) who had also received onabotulinumtoxinA. Six-month post-erenumab follow-up data were available for 42.6% (43/101) of participants. For these 43 participants, the number of headache days per month decreased significantly by 6.5days from a baseline mean (SD) of 24.8 (6.47) days to 18.3 (12) days at 6-month follow-up (P<.001); similarly, the monthly migraine days decreased significantly by 8.4days from a baseline mean of 19.1 (9.3) days to 10.7days at 6-month follow-up (P<.001). The 50% responder rate was 34.9% (15/43) for monthly headache days and 54.8% (23/43) for monthly migraine days. Of all 101 participants, 28 (27.7%) discontinued erenumab, primarily because it was ineffective (39.3%, 11/28) or because of adverse effects (42.9%, 12/28). This post-market observational study of patient experience describes response to erenumab in a real-world tertiary headache clinic with a complex patient population. Overall, these complex patients had a significant positive clinical response to erenumab, but with high rates of discontinuation. This study also noted a 1-week wearing-off response and high rates of constipation. Further post-market studies are needed to better characterize patient selection and real-world response to erenumab.

Safety and efficacy of galcanezumab in Taiwanese patients: a post-hoc analysis of phase 3 studies in episodic and chronic migraine

Objective Migraine is a chronic, disabling neurological disease affecting >1 billion people worldwide. Migraine remains undertreated in Asia, including Taiwan. Galcanezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide, a peptide firmly established in the pathophysiology of migraine, with demonstrated efficacy and safety in patients with episodic or chronic migraine. Our objective was to evaluate the efficacy and safety of galcanezumab in Taiwanese patients with episodic or chronic migraine. Methods We conducted a sub-group analysis of the Taiwanese cohort from two double-blind, placebo-controlled, Phase 3 clinical trials of galcanezumab in the prevention of episodic and chronic migraine, EVOLVE-2 (NCT02614196) and REGAIN (NCT02614261), respectively. During the EVOLVE-2 and REGAIN double-blind periods, 2092 patients were randomly assigned to receive monthly injections of either placebo, 120 mg galcanezumab (240 mg loading dose), or 240 mg galcanezumab. In REGAIN, a 9-month open-label period followed. Post-hoc analysis on the Taiwanese population across both trials included 106 patients, 45 of whom continued into the open-label period in REGAIN. Results Our findings show that galcanezumab has similar efficacy and safety in the Taiwanese population, as compared to the “All Patients” population included in the study. Galcanezumab treatment reduced the number of monthly migraine headache days, determined a higher percentage of patients with a ≥ 50% response, and positively impacted quality of life. Conclusion Galcanezumab is a promising therapeutic for the preventive treatment of migraine in the Taiwanese population.

Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study.

ObjectiveTo assess the long-term safety, tolerability, and efficacy of fremanezumab, a fully humanized monoclonal antibody approved for the preventive treatment of migraine.MethodsA 52-week, multicenter, randomized, double-blind, parallel-group study evaluated fremanezumab monthly or quarterly in adults with chronic migraine (CM) or episodic migraine (EM). Safety and tolerability were assessed by adverse event (AE) monitoring (performed by the investigators), systematic local injection-site assessments (immediately and 1 hour after injection), laboratory/vitals assessments, and immunogenicity testing. Prespecified exploratory evaluations included change from baseline in the monthly number of migraine days, headache days of at least moderate severity, and days with any acute headache medication use. Change from baseline in headache-related disability (6-item Headache Impact Test scores) was also measured.ResultsOf 1,890 patients enrolled, 551 and 559 patients with CM received quarterly and monthly dosing; 394 and 386 patients with EM received quarterly or monthly, respectively. The most commonly reported AEs were injection-site reactions (induration 33%, pain 31%, and erythema 26%). Fremanezumab reduced monthly migraine days (CM quarterly −7.2 days, CM monthly −8.0 days, EM quarterly −5.2 days, EM monthly −5.1 days) and headache days of at least moderate severity (CM quarterly −6.4 days, CM monthly −6.8 days, EM quarterly −4.4, EM monthly −4.2 days) from baseline to 12 months. Reductions in any acute headache medication use and headache-related disability were also maintained over 12 months.ConclusionsFremanezumab quarterly and fremanezumab monthly were well tolerated and demonstrated sustained improvements in monthly migraine days, headache days, and headache-related disability for up to 12 months in patients with migraine.ClinicalTrials.govNCT02638103.Classification of evidenceThis study provides Class IV evidence that long-term fremanezumab treatment is safe, well tolerated, and effective at sustaining reductions in monthly migraine and headache days.

Sudden Caffeine Withdrawal Triggers Migraine—A Randomized Controlled Trial

Objective: Assessing the effects of caffeine withdrawal on migraine.Background: The effects of caffeine withdrawal on migraineurs are at large unknown.Methods: This was a randomized, double-blind, crossover study (NCT03022838), designed to enroll 80 adults with episodic migraine and a daily consumption of 300–800 mg caffeine. Participants substituted their estimated dietary caffeine with either placebo capsules or capsulated caffeine tablets for 5 weeks before switching the comparators for 5 more weeks.Results: The study was terminated due to low recruitment. Ten subjects with a mean age of 46.3 ± 9.9 years, BMI of 24.9 ± 3.7, and a mean blood pressure of 134/83 ± 17/12 mmHg were enrolled. The average consumption of caffeine per day was 539 ± 196.3 mg. The average monthly headache days and migraine attack frequency at baseline was 11.5 ± 4.9 and 5.2 ± 1.2, respectively. At baseline Pittsburgh Sleep Quality Index was 5.8 ± 2.5 and HIT-6 was 62.8 ± 3.9. There were no differences in these or in parameters from actigraphy during the caffeine period compared with the placebo period. One subject withdrew just after entering the study. In the remaining nine, withdrawal triggered severe migraine attacks in seven, causing one more drop-out, and a typical caffeine withdrawal syndrome in two. Caffeine continuation did not trigger migraines, but one attack occurred in the wake of caffeine reintroduction.Conclusions: The study failed to answer how caffeine withdrawal affects migraineurs over time, but showed that abrupt withdrawal of caffeine is a potent trigger for migraine attacks.

The Spectrum of Response to Erenumab in Patients With Episodic Migraine and Subgroup Analysis of Patients Achieving ≥50%, ≥75%, and 100% Response.

ObjectiveTo assess the efficacy of erenumab at the ≥50%, ≥75%, and 100% reduction in monthly migraine days (MMD) response thresholds, using data from the 6‐month double‐blind treatment phase (DBTP) of the Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention (STRIVE) pivotal clinical trial.MethodsEnrolled patients with episodic migraine (EM; ≥4 MMD and <15 monthly headache days) were randomized (1:1:1) to erenumab 70 mg (n = 312), erenumab 140 mg (n = 318), or placebo (n = 316) once monthly. We determined the proportions of patients with ≥50%, ≥75% and 100% reduction in MMD over the last 3 months of the STRIVE DBTP (months 4 through 6) and conducted post hoc analyses to contextualize the treatment benefit in patient subgroups achieving, and not achieving, these response thresholds. Outcome measures included changes in MMD, acute migraine‐specific medication days (MSMD), and patient‐reported outcomes.ResultsThe proportions of patients with a reduction in MMD from baseline were greater for erenumab than for placebo at all response thresholds. As previously reported for the ≥50% response threshold, 135/312 (43.3%) of patients on erenumab 70 mg and 159/318 (50.0%) on erenumab 140 mg responded, vs 84/316 (26.6%) for placebo. At months 4 through 6, 65/312 (20.8%) and 70/318 (22.0%) of those on erenumab 70 mg and erenumab 140 mg, respectively, achieved ≥75% reductions vs 25/316 (7.9%) on placebo. A reduction of 100% response, which required no migraine days over 3 consecutive months based on observed data, was achieved by 10/312 (3.2%) of patients treated with erenumab 70 mg and 16/318 (5.0%) for erenumab 140 mg, vs 9/316 (2.8%) for placebo. At all response thresholds, responders achieved numerically greater reductions in mean MMD and MSMD, and greater improvements in disability than did the overall population; importantly, these remarkable responses were noted early. Meanwhile, 60/312 (19.2%) and 53/318 (16.7%) patients on erenumab 70 and 140 mg, respectively, had no reduction in MMD from baseline in months 4 through 6, compared with 104/316 (32.9%) patients on placebo.ConclusionsThe responses at the ≥50%, ≥75%, and 100% thresholds provide context for establishing realistic patient and physician expectations regarding the magnitude of treatment benefit that may be achieved by patients with EM responding to erenumab (STRIVE, NCT02456740).

Impulse control disorders in chronic migraine with medication overuse after onabotulinumtoxinA: A single-center prospective cohort study

Chronic migraine (CM) with medication overuse headache (MOH) is one of the most common and disabling chronic headache disorders associated with both frequencies of use of medication and behavioral alterations, including psychopathology and psychological drug dependence. Several previous studies on large patient samples have demonstrated the efficacy of Onabotulinum toxin A (OnabotA) on physical symptomatology treatment of headache, but effects on behavioral alterations remain still debate. Our study investigated the effects of OnabotA on psychiatric comorbidities and on quality of life of patients with CM and MOH that failed on traditional therapies. OnabotA was injected, according to the PREEMPT paradigm, 40 patients with CM and MOH and data on headache-related impairment, before and after the OnabotA injections were collected from the patient’s headache diaries. Data on depressive, anxiety symptomatology and impulse control disorders also were collected by means of self-report scales and a semi-structured interview. After six months, patients with CM and MOH showed a significant decrease in monthly headache attacks (from 19.3 ± 5.9 to 11.8 ± 8.5, p = 0.003), monthly headache days (from 23 ± 8.9 to 11.1 ± 6.2, p = 0.001), numbers of analgesics used per month (from 18.2 ± 6.3 to 8.5 ± 4.7, p < 0.0001). The anxiety symptomatology (p ≤ 0.003) and impulse control disorders (from 30% to 10%), but not depressive symptomatology (p = 0.81), were significantly reduced from throughout the study. The treatment with OnabotA proved beneficial effects on anxiety symptomatology and on impulse control disorders in our clinical practice with CM and MOH and further studies should shed light in larger patient samples on long-term behavioural effects.

Conversion from chronic to episodic migraine in patients treated with erenumab: real-life data from an Italian region

BackgroundMost patients treated with erenumab in clinical practice have chronic migraine (CM). We assessed the rate and possible predictors of conversion from CM to episodic migraine (EM) in a real-life study.Main bodyWe performed a subgroup analysis of patients treated with erenumab from January 2019 to February 2020 in the Abruzzo region, central Italy. Treatment was provided according to current clinical practice. For the purpose of the present study, we included patients fulfilling the definition of CM for the three months preceding erenumab treatment and with at least 6 months of follow-up after treatment. We assessed the rate of conversion to EM from baseline to Months 4–6 of treatment and during each month of treatment. To test the clinical validity of conversion to EM, we also assessed the decrease in monthly headache days (MHDs), acute medication days, and median headache intensity on a Numerical Rating Scale (NRS). We included in our study 91 patients with CM. At Months 4–6, 62 patients (68.1%) converted from CM to EM; the proportion of converters increased from Month 1 to Month 5. In the overall group of patients, median MHDs decreased from 26.5 (IQR 20–30) to 7.5 (IQR 5–16; P < 0.001) compared with baseline, while median acute medication days decreased from 21 (IQR 16–30) to 6 (IQR 3–10; P < 0.001) and median NRS scores decreased from 8 (IQR 7–9) to 6 (IQR 4–7; P < 0.001). Significant decreases were found both in converters and in non-converters. We found no significant predictors of conversion to EM among the patients’ baseline characteristics.ConclusionsIn our study, two thirds of patients with CM converted to EM during 6 months of treatment with erenumab. MHDs, acute medication use, and headache intensity decreased regardless of conversion from CM to EM.

Economic consequences of migraine in Sweden and implications for the cost-effectiveness of onabotulinumtoxinA (Botox) for chronic migraine in Sweden and Norway

BackgroundMigraine is a common and incapacitating condition, with severe impact on the quality of life (QoL) of the afflicted and their families, and negative economic consequences through decreased workforce participation, reduced functional ability and elevated healthcare costs. This study aimed to describe the economic consequences of migraine in Sweden using cost of illness survey data and, based on this data, assess the cost-effectiveness of onabotulinumtoxinA (Botox) for the treatment of chronic migraine in Sweden and Norway.MethodsA survey study was conducted in Swedish migraine patients, with questions on patient characteristics, headache frequency and severity, effect on daily activities and work, QoL, health resource utilization, and medication use. Resulting costs were estimated as annual averages over subgroups of average monthly headache days. Some results were used to inform a Markov cost-effectiveness chronic migraine model. The model was adapted to Sweden and Norway using local data. The analysis perspective was semi-societal. Results’ robustness was tested using one-way, structural, and probabilistic sensitivity analyses.ResultsResults from the cost of illness analysis (n = 454) indicated a clear correlation between decreased QoL and increased costs with increasing monthly headache days. Total annual costs ranged from EUR 6221 in patients with 0–4 headache days per month, to EUR 57,832 in patients with 25–31. Indirect costs made up the majority of costs, ranging from 82% of total costs in the 0–4 headache days group, to 91% in 25–31 headache days. The cost-effectiveness analyses indicated that in Sweden, Botox was associated with 0.223 additional QALYs at an additional cost of EUR 4126 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 18,506. In Norway, Botox was associated with 0.216 additional QALYs at an additional cost of EUR 4301 compared to placebo, resulting in an ICER of EUR 19,954.ConclusionsIn people with migraine, an increase in monthly headache days is clearly related to lower QoL and higher costs, indicating considerable potential costs-savings in reducing the number of headache days. The main cost driver for migraine is indirect costs. Botox reduces headache days and is a cost-effective treatment for chronic migraine in Sweden and Norway.