Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved in the USA, EU, and Japan for the preventive treatment of migraine in adults. We evaluated the long-term safety, efficacy, and functional outcomes of atogepant for the preventive treatment of migraine in Japanese participants. This open-label, 52-week, long-term safety extension study evaluated atogepant 60mg once daily for the preventive treatment of migraine in Japanese participants. The study enrolled participants with chronic migraine (CM) who completed the phase3 PROGRESS trial and de novo participants with episodic migraine (EM). The primary objective was the safety and tolerability of atogepant. Efficacy and functional outcomes were exploratory endpoints. Of 204 Japanese participants screened, 186 were enrolled and included in the safety population (CM, n = 155; EM, n = 31) and 180 in the modified intent-to-treat population (CM, n = 150; EM, n = 30). Treatment-emergent adverse events (TEAEs) occurred in 88.7% of participants. TEAEs occurring ≥ 10% were pyrexia (29.0%), nasopharyngitis (16.1%), and constipation (11.3%). Concurrent COVID-19 vaccination attributed to several TEAEs, including pyrexia. Serious TEAEs occurred in 3.8% of participants and none were considered related to atogepant by the investigator. TEAEs leading to discontinuation occurred in 4.8% of participants. Alanine aminotransferase and/or aspartate aminotransferase ≥ 3 × the upper limit of normal occurred in 4.8% of participants; none met criteria for Hy's law. The least squares mean change from baseline in monthly migraine days was - 6.4days in PROGRESS CM completers and - 3.4days in de novo EM participants at weeks1-4 and was consistent over 52weeks. Similar improvements were observed for the other efficacy and functional outcomes. The safety profile of atogepant in Japanese participants was consistent with the known safety profile in the global population. No new safety signals were identified. Improvements in efficacy and functional outcomes persisted over 52weeks. NCT04437433; https://clinicaltrials.gov/study/NCT04437433.

Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for migraine prevention; however, real-world data from the Middle East and North Africa (MENA) region remain limited. This study evaluated the efficacy and safety of atogepant in patients with chronic and episodic migraine in the United Arab Emirates. This retrospective study included adult patients (≥ 18years) diagnosed with chronic or episodic migraine who received atogepant for at least 6months. Clinical data were extracted from electronic medical records at the American Center for Psychiatry and Neurology, Abu Dhabi. Monthly migraine days (MMD) at baseline were compared with follow-up MMD documented at visits occurring at least every 2months. Safety outcomes were assessed through descriptive analysis of reported adverse events (AEs) in the all-exposed population. Sensitivity analyses (non-responder imputation, baseline observation carried forward, multiple imputation under MAR, and tipping point analysis) were conducted to evaluate the robustness of efficacy results in the presence of missing data. Of 86 patients identified, 59 met the inclusion criteria and their data were analyzed. Among these, 39% had chronic migraine and 61% had episodic migraine. The majority were female patients (86.4%) and Emirati nationals (69%). The mean baseline MMD was 12 (SD 8.1), which decreased to 4 (SD 5.2) at the most recent follow-up. Overall, 71% achieved ≥ 50% reduction in MMD, 20% achieved < 50% reduction, and 9% experienced no change. Paired-sample ttest demonstrated a significant reduction in MMD t(58) = 9.44, p < 0.001. Adverse events were reported in 10.5% (9/86) of patients, most commonly constipation and nausea. Most patients experiencing AEs (78%) continued treatment, while two discontinued. In this real-world cohort from the UAE, atogepant was associated with significant reductions in monthly migraine days in both patients with chronic and episodic migraine and demonstrated a favorable safety and tolerability profile.

Migraine is a common and disabling neurological disorder in children, often requiring preventive treatment. This study aimed to compare the efficacy and tolerability of cinnarizine and topiramate in the prophylaxis of migraine in children and adolescents. In this randomized, double-blind, parallel-group clinical trial, 96 children aged 6-15 years with a diagnosis of migraine according to the International Classification of Headache Disorders (ICHD-3) [1], including both migraine with and without aura, without restriction to specific subtypes were enrolled. Participants were randomly assigned to receive either cinnarizine (25mg once daily) or topiramate (25mg once daily) for 12 weeks. Migraine attack frequency and severity were recorded using headache diaries at baseline, one month, and three months after treatment initiation. The primary outcome was the change in monthly migraine attack frequency. Secondary outcomes included changes in headache severity and the occurrence of adverse events. Between-group comparisons were performed using the Mann-Whitney U test, and within-group changes over time were analyzed using the Friedman test. Both cinnarizine and topiramate significantly reduced monthly migraine attack frequency and headache severity over the 12-week treatment period (P < 0.001 for within-group comparisons). At three months, the median number of migraine attacks decreased to two attacks per month in both groups, with no statistically significant difference observed between the two treatments (P = 0.81). Headache severity scores also improved significantly in both groups, and no between-group differences were observed at follow-up (P = 0.74). Both medications were generally well tolerated, with no statistically significant differences in the incidence of adverse events between groups. Appetite reduction was reported in 4.2% of the cinnarizine group versus 14.6% of the topiramate group. While a numerically lower incidence of appetite reduction was observed in the cinnarizine group (4.2% vs. 14.6%), this difference was not statistically significant (P = 0.159, Fisher's exact test; OR = 0.255, 95% CI: 0.05-1.27). Both cinnarizine and topiramate significantly reduced the frequency and severity of migraine attacks in children. No statistically significant difference in efficacy was detected between the two treatments. A numerically lower incidence of appetite reduction was observed with cinnarizine, although this difference was not statistically significant. Larger studies are needed to evaluate potential differences in tolerability. Iranian Registry of Clinical Trials (IRCT) IRCT20221108056444N1. Registered 12 February 2023 Retrospectively registered, https://www.en.irct.ir/trial/66774.

Migraine is a primary headache disorder wherein vascular changes are well known. We aimed to evaluate the retinal and choroidal parameters in migraine patients longitudinally, with a particular focus on treatment-related changes. We conducted a prospective longitudinal study of 45 patients with migraine (ICHD-3 criteria) who were indicated for prophylactic treatment. The patients were evaluated clinically using the visual analogue scale (VAS), monthly migraine days (MMD), migraine disability assessment score (MIDAS), and Optical Coherence Tomography (OCT) at baseline and after 3 months of follow-up. The peripapillary retinal nerve fibre layer (PPRNFL), peripapillary choroid thickness (PPCHT), subfoveal choroid thickness (SFC), ganglion cell layer (GCL), and central macular thickness (CMT) were the parameters assessed using OCT. 45 age- and gender-matched healthy controls were recruited for comparison of baseline parameters. The majority of patients (38/45) were females, and the mean age was 37.3 ± 10.0 years. The PPRNFL, PPCHT, SFC LE, GCL, and CMT were thinner in patients than in controls. All parameters, except the GCL and CMT, increased significantly during follow-up after 3 months of prophylactic treatment. This longitudinal study demonstrated partial structural recovery, suggesting that some retinal and choroidal changes in migraine may be reversible. Our findings support the role of these OCT parameters as surrogate markers of disease burden and treatment response in migraine. Large-scale, multicentre prospective studies with longer follow-up are warranted to evaluate the prognostic utility of OCT parameters in migraine.

To compare the 3-month effectiveness of galcanezumab with select traditional oral migraine preventive (TOMP) medications recommended by scientific societies (TOMP efficacy subset) and with the most frequently used individual TOMP medications. Multiple TOMP medications (within classes of beta-blockers, anticonvulsants, tricyclic antidepressants, angiotensin II receptor antagonists, and calcium channel blockers) originally developed to treat other conditions are used for migraine prevention. In a recent real-world analysis comparing galcanezumab with a broader classification of TOMP, a significantly greater proportion of patients treated with galcanezumab achieved a clinically meaningful response at 3 months (reduction from baseline in monthly migraine headache days) (46.6% vs. 34.5%, p < 0.001). Treatment selection is often individualized based on patients' historical and current clinical profiles, preferences, and comorbid conditions. Comparing the real-world effectiveness of galcanezumab with specific TOMP using stringent criteria based on established efficacy at a global level will provide additional insights. The TRIUMPH (preventive TReatment of mIgraine: oUtcoMes for Patients in real-world Healthcare systems) study is an ongoing, international, prospective observational cohort study comparing the effectiveness of galcanezumab with other preventives (EUPAS33068). A priori sample size was achieved, and interim data (Feb 25, 2020, to Feb 9, 2023) were analyzed. The current analysis compared patients with migraine initiating galcanezumab versus the TOMP efficacy subset (drugs with established/probable efficacy based on the 2021 American Headache Society consensus statement incorporating the American Academy of Neurology classification of evidence and consistent with the European Headache Federation/European Academy of Neurology and Japanese Society of Neurology/Japanese Headache Society). Galcanezumab was also compared with the most frequently used individual TOMP drugs in the TRIUMPH study. Reduction in monthly migraine headache days (≥50%: episodic migraine, ≥30%: chronic migraine) from baseline to 3 months was assessed after adjusting for baseline cohort differences. At the time of this analysis, 2398 patients from the United States, Japan, Germany, Italy, the United Kingdom, Spain, and the United Arab Emirates had completed baseline assessments. Topiramate (n = 343) and amitriptyline (n = 240) were the most frequently used TOMP drugs. At 3 months, the galcanezumab cohort (n = 1065) had a greater weighted proportion of responders versus the TOMP efficacy subset (n = 916) (48.3% [95% confidence interval [CI]: 45.1%, 51.6%] vs. 35.9% [95% CI: 32.6%, 39.3%]; p < 0.001), topiramate (n = 343) (48.8% [95% CI: 45.7%, 51.9%] vs. 37.2% [95% CI: 31.2%, 43.7%]), and amitriptyline (n = 240) (49.7% [95% CI: 46.6%, 52.8%] vs. 23.3% [95% CI: 17.5%, 30.4%]) cohorts. In this real-world study, galcanezumab induced a clinically meaningful reduction in migraine headache days in a higher proportion of patients than TOMP medications classified as efficacious, including topiramate and amitriptyline. EUPAS33068. Limited information exists on how the use of traditional oral migraine preventive (TOMP) medications compares to the effectiveness of galcanezumab. In this study, we compared the reduction in monthly migraine days after 3 months among adult patients initiating or switching to either a TOMP medication or galcanezumab. Patients receiving galcanezumab had a greater response after 3 months than those receiving TOMP medications, suggesting better real-world effectiveness of galcanezumab.

Galcanezumab, a humanized calcitonin gene-related peptide monoclonal antibody, is approved in Japan for migraine prevention, but real-world effectiveness data are limited. This analysis describes the 3-month treatment outcomes of galcanezumab and traditional oral migraine preventive medications (TOMPs) in the TReatment of mIgraine: oUtcoMes for Patients in real-world Healthcare systems (TRIUMPH) study's Japan subgroup. TRIUMPH, an international, prospective, observational, 24-month cohort study, included adults with migraine who initiated or switched to galcanezumab or TOMP. Japan subgroup data were collected from September 2021 to November 2024. Physicians decided on the treatment course in routine clinical practice. The primary outcome was achieving a clinically meaningful response at 3months, defined as a ≥ 50% reduction in monthly migraine headache days for episodic migraine and ≥ 30% for chronic migraine. Secondary outcomes included changes in migraine headache days and patient-reported outcomes (PROs): Migraine Disability Assessment (MIDAS), Headache Impact Test-6 (HIT-6), Migraine Interictal Burden Scale-4 (MIBS-4), Migraine-Specific Quality of Life Questionnaire (MSQv2.1), and Work Productivity and Activity Impairment (WPAI). Inverse probability of treatment weighting was used to adjust for baseline differences in the primary analysis. No alpha was allocated for comparative formal testing between treatment groups. Of 846 patients, 469 received galcanezumab and 377 received TOMPs. In the galcanezumab and TOMP groups, the 3-month weighted response rates were 59.4% and 38.3%, and the reduction in mean migraine headache days from baseline was - 6.2 [95% confidence interval (CI): - 6.9, - 5.5] and - 4.2 (95% CI: - 5.0, - 3.4), respectively. Mean change at 3months from baseline was numerically higher in the galcanezumab group than in the TOMP group for all the PROs. Patients receiving galcanezumab had numerically greater 3-month response rates and experienced improved PROs after initiating galcanezumab. These real-world findings may help physicians make treatment decisions in clinical settings. EU PAS Register number-EUPAS33068.

Introduction . The treatment of patients with chronic migraine (CM) and medication overuse headache (MOH) is an actual problem in neurology. Predictors of treatment effectiveness for CM and MOH have been poorly studied. Aim . To study the prognostic factors of therapeutic response in CM. Materials and methods . 54 patients (11 men, 43 women) with CM aged 18 to 50 years (average age 39 years), with or without MOH received preventive treatment for 12 months with evaluation of results every 2 months. Patients kept a headache diary. The questionnaire took place during each visit and included assessments using the VAS (Visual Analog Scale), SF-36 (SF-36 Health Status Survey), MIDAS (Migraine Disability Assessment), MSQ v2.1 (Migraine Specific Quality of Life Questionnaire version 2.1), Morisky – Green Medication Adherence Scale, Sleep Quality Questionnaire, CSI-A (Central Sensitization Inventory), LDQ (Leeds Dependence Questionnaire), HIT-6 (Headache Impact Test-6), HADS (Hospital Anxiety and Depression Scale). Results . The baseline monthly migraine frequency was associated with the MSQ v2.1 (restrictive function: β = -0.17, preventive function: β = -0.14, emotional function: β = -0.06, p &lt; 0.001), SF-36 (PH: β = -0.37, MH: β = -0.02, p &lt; 0.001), LDQ (β = 0.5, p &lt; 0.001), HIT-6 (β = 0.47, p &lt; 0.001), CSI-A (β = 0.19, p &lt; 0.001) scores. The baseline MIDAS score was associated with the results of the LDQ (β = 6.1, р &lt; 0.001), CSI-A (β = 2, р &lt; 0.001), HIT-6 (β = 3.46, р &lt; 0.001), НАDS-A (β = 4.5, р &lt; 0.001), HADS-D (β = 2.82, р = 0.014), SF-36 (PH: β = -3.4, MH: β = -2, р &lt; 0.001), MSQ v2.1 (restrictive function: β = -1.66, preventive function: β = -1.77, emotional function: β = -0.9, p &lt; 0.001) and Sleep Quality Questionnaire (β = -4.5, р &lt; 0.001). However, these factors were not associated with the dynamics of reduction in the frequency of headaches and MIDAS. On the background of preventive therapy headache frequency decreased by 2 episodes per month (β = -2.15, p &lt; 0.001), and the MIDAS score decreased by almost 9 points (β = -8.95, p &lt; 0.001). MOH was not a significant predictor of migraine dynamics (p = 0.072) and severity on the MIDAS scale (p = 0.24). Conclusion . The duration of preventive treatment under the control of a specialist is the main predictor of a positive therapeutic response in CM and MOH.

Headache diaries are the gold standard for assessing preventive migraine treatments but can be burdensome. The Migraine Disability Assessment (MIDAS) and the six-item Headache Impact Test (HIT-6) offer alternatives for monitoring treatment response, though their effectiveness in identifying treatment responders is unclear relative to diary-based measures. This study evaluated how well MIDAS and HIT-6 distinguish responders from non-responders to erenumab, and aimed to determine cut-off scores that best align with a ≥ 50% reduction in monthly migraine days (MMDs). This prospective, open-label study enrolled adults with migraine who received 140 mg erenumab for 24 weeks. Treatment response was a ≥ 50% reduction inMMDs based on diary data. MIDAS and HIT-6 were completed at baseline, Week 12, and Week 24. Discriminative ability and optimal cut-offs were determined using receiver operating characteristic curve analysis. Among 582 participants, 300 individuals (52%) achieved a ≥ 50% reduction in MMDs. MIDAS and HIT-6 demonstrated fair discriminative ability in identifying treatment responders, with area under the curve values ranging from 0.71 to 0.77. The optimal MIDAS cut-offs were either a 16-point absolute reduction (78% sensitivity, 60% specificity) or a 49% relative reduction (82% sensitivity, 64% specificity). For HIT-6, optimal thresholds included an 8-point reduction (53% sensitivity, 84% specificity) or a 12% relative reduction (54% sensitivity, 84% specificity). Sensitivity analyses using alternative response definitions confirmed the primary findings. Although MIDAS and HIT-6 contribute meaningful information on treatment-related disability reduction, these retrospective tools lack sufficient precision to replace prospective headache diaries in assessing response to erenumab. NCT04603976.

This study aimed to evaluate demographic characteristics, treatment effectiveness, and safety outcomes in patients with migraine undergoing anti-calcitonin gene-related peptide (CGRP) treatments regarding the presence of autoimmune diseases. CGRP has an important role in migraine pathophysiology through neuronal modulation in the trigeminovascular nociceptive system and activation of neuro-inflammatory cascades. We hypothesized that autoimmune diseases may influence treatment response and safety profiles in patients with migraine treated with anti-CGRP treatments. This was a retrospective multicenter, age- and sex-matched cohort study in headache units/headache clinics in Spain and United Kingdom between May 2024 and May 2025 including patients treated with CGRP monoclonal antibodies from prospectively collected cohorts. Patients were assessed for demographics, migraine-related characteristics, treatment effectiveness (monthly migraine days [MMD] and/or monthly headache days [MHD]), and safety outcomes. The main outcome was the effectiveness measured by ≥50% response rate in MMD between the two groups. Secondary outcomes included other effectiveness measurements regarding the number of MMD and MHD and treatment emerging adverse events. A total of 388 patients with migraine under anti-CGRP treatments (194 with autoimmune diseases and 194 age- and sex-matched controls without autoimmune diseases) were included. The proportion of patients achieving a ≥50% response rate in MMD was higher in patients without autoimmune diseases at 6 (69% vs. 53%; p = 0.006) and 9 months (74% vs. 52%; p = 0.006). Treatment emerging adverse events were comparable between the two groups (35% vs. 38%; p = 0.575). Patients with autoimmune disease had a significantly lower likelihood of achieving a ≥50% response in MMD compared with those without autoimmune disease (adjusted odds ratio, 0.61; 95% confidence interval, 0.44-0.85; p = 0.006), independent of comorbid depression and medication overuse. Our study shows that anti-CGRP treatments are effective and safe for patients with migraine regardless the presence of autoimmune diseases, although an increased treatment response in patient without autoimmune disorders compared to patients with autoimmune disorders was observed. These findings highlight the need for early intervention, tailored strategies, and vigilant monitoring in patients with migraine and autoimmune disorders. Further research should explore immunomodulatory approaches to enhance outcomes.

Background Despite advances in migraine management, some patients fail to respond to preventive treatments for migraine. We aimed to assess the comparative effects of available pharmacological prophylaxis in adults with a treatment failure history. Methods We searched Medline, Embase, Cochrane Central, PsycINFO, Web of Science, and Scopus up to July 2025. Pairs of reviewers independently screened titles, abstracts, and full-text articles to identify randomized controlled trials of prophylactic pharmacological interventions that enrolled adults diagnosed with chronic or episodic migraine and a prior preventive treatment failure. We performed a frequentist random-effects network meta-analysis and used the GRADE approach to assess the certainty of evidence. Results We included 18 randomized trials (7281 participants). Compared to placebo, low certainty evidence suggest fremanezumab [mean difference (MD) −3.30 (95% CI: −4.11 to −2.49)], eptinezumab [MD −3.35 (95% CI: −4.38 to −2.32)], galcanezumab [MD −2.73 (95% CI: −3.43 to −2.03)], atogepant [MD −2.30 (95% CI: −3.47 to −1.13)], and erenumab [MD −2.20 (95% CI: −2.72 to −1.68)] may be among the most effective in reducing the monthly migraine headache days. Low to moderate certainty evidence suggests that, compared with placebo, galcanezumab [relative risk (RR) 1.94 (95% CI: 1.52 to 2.48)], fremanezumab [RR 3.98 (95% CI: 2.40 to 6.59)], atogepant [RR 2.80 (95% CI: 1.73 to 4.54)], erenumab [RR 2.56 (95% CI: 2.01 to 3.26)], and eptinezumab [RR 2.35 (95% CI: 1.61 to 3.42)] may increase the likelihood of achieving a 50% response rate. Conclusion Evidence for migraine patients with prior preventive treatment failure is limited. Low- to moderate-certainty data suggest that CGRP-targeted therapies may provide some benefit and are generally tolerable, but the available evidence is driven by a few industry-sponsored trials. Additional independent, well-powered studies with longer follow-up are needed to strengthen the evidence base. Registration number PROSPERO (CRD42024547860).

BackgroundTreatment with onabotulinumtoxinA is effective in reducing migraine day frequency and duration in individuals with chronic migraine (CM), but given the severity of the disease, those with CM often need additional treatment to achieve optimal outcomes. Combining preventive treatments with distinctly different physiological targets may yield greater benefit than monotherapy. This study evaluated the safety, tolerability, and efficacy of adding atogepant to onabotulinumtoxinA for preventive treatment of CM.MethodsIn this 24-week, Phase 3, open-label, single arm, multicenter study (NCT05216263), 75 participants on a stable dose of onabotulinumtoxinA (155-200U) with baseline mean monthly migraine days (MMDs) of 8-23 (inclusive) received add-on atogepant 60 mg once daily. Primary safety endpoints included treatment-emergent adverse events (TEAEs), and exploratory efficacy endpoints included changes in MMDs, changes in mean monthly headache days (MHDs) and responder rates (RRs) (≥50%, ≥75%, and 100% MMDs) over Weeks 1-12, Weeks 13-24, and at each 4-week interval.ResultsThe mean age of study participants was 48 (13.68) years (mean (SD)); 89% were women, and 97% were white. Participants had an established CM diagnosis for 15 (13.27) years (mean (SD)) and had been treated with onabotulinumtoxinA for 4 (3.45) years (mean (SD)). In the safety population (n = 75), the incidence of TEAEs was 65.3%. TEAEs occurring in ≥5% of participants were constipation (n = 12, 16.0%), nausea (n = 10, 13.3%), and urinary tract infection (n = 6, 8.0%). An AE was considered the primary reason for drug discontinuation in 2 (2.7%) participants. Treatment-emergent serious AEs (TESAEs) occurred in 2 participants; neither were considered treatment-related by the investigators. In the modified intention-to-treat population (n = 72), the least squares (LS) mean change from baseline of 14.34 MMDs was -6.45 MMDs (95% CI: -7.7, -5.1) at Weeks 1-4, -6.89 MMDs (95% CI: -8.1, -5.6) across Weeks 1-12, and -7.20 MMDs (95% CI: -8.4, -5.9) across Weeks 13-24. The least square mean change from baseline of 17.00 MHDs was -6.57 MHDs (95% CI: -7.8, -5.3) at Weeks 1-4, -7.33 MHDs (95% CI: -8.6, -6.0) across Weeks 1-12 and -8.15 MHDs (95% CI: -9.4, -6.8) across Weeks 13-24. A ≥ 50% RR in MMD was achieved by 54.2% and 61.9% of participants across Weeks 1-12 and Weeks 13-24 of combined treatment, respectively. A ≥ 75% RR was achieved by 30.6% and 38.1% of participants.ConclusionsIn this study, combination preventive treatment for CM with onabotulinumtoxinA and atogepant was safe and generally well-tolerated. Furthermore, the addition of atogepant to those stable on onabotulinumtoxinA resulted in clinically meaningful reductions in migraine days and improvement in responder rates, suggesting a benefit of combining treatments with distinct and complementary mechanisms of action for suppression of CM.Trial RegistrationClinical Trials.gov NCT05216263.

AimAtogepant is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for migraine prevention. This study primarily evaluated its effectiveness and safety in real-world clinical practice, focusing on patients with treatment-resistant migraine, defined according to the European Headache Federation (EHF) criteria as failure of at least three classes of preventive medications, including onabotulinumtoxinA or anti-CGRP monoclonal antibodies (mAbs).MethodsThis prospective multicentre study was conducted across 15 tertiary Headache Units in Spain. Demographic and clinical data, prior preventives, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were systematically collected at baseline, 3 months (primary endpoint), and/or 6 months (secondary endpoint).ResultsA total of 513 patients were enrolled (mean age 48 years; 88% women). The 3-month analysis included 455 patients, with median MHD decreasing from 21 (IQR 15-30) to 14 (IQR 6-30) and MMD from 14 (IQR 10-20) to 8 (IQR 3-15) (both p < 0.0001). A ≥ 50% reduction was achieved by 34% (MHD) and 29% (MMD), with ≥75% responses in 16% and 13%. Adverse events were mostly mild, mainly constipation (30%) and nausea (18%), and the 3-month discontinuation rate was 11.8%. Responders had shorter migraine chronicity, less analgesic overuse, and fewer prior preventive failures. Although prior inadequate response to anti-CGRP mAbs reduced the likelihood of improvement, it did not prevent meaningful benefit. At analysis, 151 patients had reached the 6-month visit, showing further improvement (MHD 10 [IQR 5-20]; MMD 6 [IQR 4-12]) and fewer adverse events.ConclusionsAtogepant showed robust real-world effectiveness and good tolerability in a large, treatment-resistant migraine cohort, with clinically meaningful improvement at 3 months and incremental benefit in the subgroup evaluated at 6 months. Lower migraine chronicity and fewer prior preventive failures were associated with better outcomes, supporting the earlier introduction of anti-CGRP therapies in clinical practice.Trial RegistrationClinical Trials.gov NCT06241313.

Efficacy of Erenumab in Patients With Treatment-Resistant Chronic Migraine and Medication Overuse Headache

Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies effectively prevent migraine headache, but their impact on aura is unclear. The aim of this study was to characterize longitudinal changes in migraine aura frequency during and after preventive treatment with erenumab in adults with frequent, prospectively confirmed migraine aura. This prospective, longitudinal, single-center investigation enrolled adults diagnosed with migraine with aura who reported ≥ 4 monthly migraine days and ≥ 2 monthly aura days during a 4-week baseline period. Erenumab was administered subcutaneously at a dose of 140mg every 4 weeks for 24 weeks, followed by a 12-week post-treatment follow-up period. Headache and aura outcomes were recorded prospectively using standardized headache diaries completed throughout baseline, treatment, and follow-up. The primary outcome consisted of the mean absolute change in monthly aura days from baseline, evaluated at four-week intervals across the study period. Eighty participants with migraine with aura provided outcome data eligible for analysis. The mean (SD) age was 43.1 (11.9) years, and 74 participants (93%) were female. At baseline, participants reported a mean of 8.0 (SD, 5.1) monthly aura days. After 24 weeks of treatment, the mean change in monthly aura days was - 4.9 (95% CI, - 5.8 to - 4.0) compared to baseline (p < 0.001). This improvement was partially sustained during the subsequent 12-week post-treatment follow-up, with a mean change of - 3.2 days (95% CI, - 4.2 to - 2.2) relative to baseline (p < 0.001). Exploratory analyses identified that greater reductions in monthly aura days were independently associated with a higher baseline number of monthly aura days (β = -0.60; 95% CI, - 0.72 to - 0.47; p < 0.001) and a greater reduction in monthly migraine days (β = -0.36; 95% CI, - 0.49 to - 0.23; p < 0.001). Preventive treatment with erenumab was associated with substantial and sustained reductions in aura frequency in adults with frequent migraine aura. These findings underscore the relevance of incorporating aura-specific outcomes into future controlled trials evaluating preventive migraine treatments. The study was registered on ClinicalTrials.gov (NCT04603976).

Background and ObjectivesMedication-overuse headache (MOH) commonly co-occurs with and complicates chronic migraine (CM). This trial evaluated efficacy and safety of eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention—combined with a standardized brief educational intervention (BEI)—in adults with CM and MOH. We report results from the 12-week placebo-controlled period, of which weeks 1–4 was the primary time point.MethodsThe phase 4, double-blind, placebo-controlled RESOLUTION trial was conducted at 76 specialist clinics across 11 countries. Eligible participants were adults diagnosed with CM and MOH and were randomized 1:1 to eptinezumab 100 mg IV with BEI or placebo IV with BEI. The primary end point was mean change from baseline in monthly migraine days (MMDs; weeks 1–4). Key secondary end points (multiplicity-controlled) included changes from baseline in monthly headache days, monthly days with acute migraine medication use, and average daily pain, as well as fulfillment of thresholds defining CM and MOH. Treatment-emergent adverse events (TEAEs) were assessed.ResultsBetween July 2022 and March 2025, 608 participants were randomized, and 596 (98%) completed the placebo-controlled period. Of 604 participants treated, 517 (86%) were female and 87 (14%) were male; the mean age was 45.5 years (SD 12.0). The primary end point, mean change from baseline in MMDs (weeks 1–4), favored eptinezumab with BEI vs placebo with BEI (−6.9 vs −3.7; group difference −3.2; 95% CI −4.2 to −2.2; p < 0.0001). All key secondary end points showed statistically significant improvements with eptinezumab with BEI vs placebo with BEI; the greater reductions in disease burden observed during weeks 1–4 were sustained through weeks 1–12. The proportion of participants with TEAEs was similar with eptinezumab (41.9%) and placebo (36.9%); no new safety signals were identified.DiscussionIn adults with CM and MOH who also received patient education, eptinezumab was statistically superior to placebo on the primary and all key secondary end points, reducing disease burden as early as weeks 1–4 and throughout weeks 1–12. Eptinezumab was generally well tolerated, with no new safety signals identified. Together, data from this trial indicate that eptinezumab in combination with patient education is an effective treatment for reducing disease burden in patients living with CM complicated by medication overuse.Trial Registration InformationClinicalTrials.gov Identifier: NCT05452239 (clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40); EU CTR Number: 2024-510729-24-00 (euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-510729-24-00). EudraCT Number obtained: May 25, 2021. ClinicalTrials.gov Identifier obtained: July 6, 2022. First patient enrolled: July 1, 2022.Classification of EvidenceThis clinical trial provides Class I evidence that eptinezumab with patient education is superior to placebo with patient education in reducing MMDs in adults with CM and MOH.

Although migraine is the second most prevalent form of headache, its preventive treatment has some contraindications and complications. It has been postulated that lacosamide might inhibit CGRP release in the trigeminal system, which could contribute to migraine management. We aimed to evaluate the efficacy and safety of lacosamide as an alternative medication to propranolol for preventing episodic migraine, especially in patients who cannot tolerate propranolol and approved antiseizure medicines for migraine prevention. We recruited patients with episodic migraines; we had two groups: lacosamide group who received lacosamide 50mg once daily for 1 week, then twice daily from the 8th day till the 90th day; propranolol group who received propranolol 40mg twice daily for 1 week, then 80mg twice daily from the 8th till the 90th day. 574 completed the study. In episodic migraine patients, there was no significant difference in the MMD in the last 4 weeks of treatment compared to baseline, the percentage of patients who achieved > 50% reduction in migraine days, reduction in MMD that required acute medication in the last 4 weeks, reduction in HIT score compared to baseline in both groups with P-values 0.13, 0.22, 0.57, and 0.61 respectively. In episodic migraine patients, the regular use of lacosamide 50 mg Bid for 3 months yielded reductions in the monthly migraine days, migraine days that required acute medications, and HIT6 score comparable to those achieved using propranolol 80mg Bid. Lacosamide was well-tolerated by migraine patients. Trial registration: registered on clinicaltrial.gov, NCT05851781-30/04/2023.

BackgroundMigraine is a disabling neurological disorder that greatly impacts quality of life and productivity. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have recently improved preventive migraine therapy. However, some patients show limited efficacy, loss of response, or adverse effects, prompting interest in switching between mAbs.ObjectiveThe objective of this work is to evaluate the effectiveness of switching between mAbs in chronic migraine/high-frequency episodic migraine (CM/HFEM) patients and to identify potential clinical predictors of response.MethodsThis single-centre, real-life, prospective study was conducted in a tertiary hospital headache unit which includes patients with CM or HFEM who switched from one mAb to another without a treatment gap greater than 1 month. Monthly headache days (MHDs), monthly migraine days (MMDs), monthly analgesic consumption (MAC), and medication overuse (MO) were recorded 3 months before and at three and 6 months after switching. Subanalyses were performed based on the mechanism of action (anti-ligand vs. anti-receptor), reason for switch (lack or loss of efficacy), and clinical predictors.ResultsEighty-five patients (52.2 ± 9.6 years; 87.1% female; 95.3% CM) were included. At 3 months post-switch, reductions were observed in MHDs (−5.8 days, p < 0.001), MMDs (−5.8 days, p < 0.001), MAC (−5.6 days, p < 0.001), and MO (−22.2%, p = 0.001). At 6 months, these improvements persisted. A ≥ 50% response was achieved in 29.4% (25/85) of patients at month 3 and 32.9% (28/85) at month 6. One-third of patients whose switch included a change in mechanism of action responded, while none of those who underwent anti-ligand to anti-ligand switch showed a reduction of MHDs >50%. Both patients with loss and lack of efficacy to the first mAb improved significantly, though early response was more frequent among those with prior loss of efficacy. Obesity and concomitant tension-type headache were associated with poorer early response, while migraine with aura predicted better late response.ConclusionSwitching between mAbs could be an effective strategy for some CM and HFEM patients who fail initial mAb therapy, rescuing approximately one-third of non-responders. The therapeutic benefit seems to be greater when the second antibody targets a different mechanism of action. These real-world findings support the use of individualized switching strategies in refractory migraine management.

Background: Despite the availability of traditional pharmacotherapies, including triptans and nonsteroidal anti-inflammatory drugs (NSAIDs), clinical value is often limited by suboptimal efficacy, significant cardiovascular contraindications, and the risk of medication-overuse headache (MOH). This study aims to evaluate the clinical efficacy and safety of rapidly developing calcitonin gene-related peptide (CGRP) receptor antagonists named ‘gepants’. Material and methods: A systematic review of scientific literature was performed to evaluate the efficacy of novel antimigraine agents. A structured search of the PubMed database was conducted using keywords including "migraine", "gepant", and "CGRP receptor antagonists." Emphasis was placed on clinical trials, RCTs, and meta-analyses, supplemented by references to neurological textbooks to provide clinical context. Results: Analysis of clinical data indicates that daily administered gepants reduce mean monthly migraine days (MMDs) compared to placebo in preventive treatment model. Furthermore, gepants proved their efficacy in acute migraine treatment, providing pain relief and the absence of the most bothersome symptoms (MBS). Multiple studies evaluating novel gepants have reported safety profiles comparable to placebo. In addition, gepants do not exert vasoconstrictive effects, making them a viable candidate for triptan-unsuitable patients or those who had documented adverse events (AEs) of traditional oral preventive medications (OPMs). Conclusions: Novel CGRP receptor antagonists represent a significant advancement in migraine therapy. By providing high tolerability and efficacy without the risk of MOH, hepatotoxicity or cardiovascular events, gepants emerge as a transformative option for both acute relief and prophylaxis in adult triptan-unsuitable patients suffering from migraine.

Background: Adolescent migraine is highly prevalent and associated with substantial functional and psychosocial burden. Conventional oral preventives are widely used off-label with limited pediatric efficacy and frequent tolerability problems. Real-world data on calcitonin gene-related peptide (CGRP) monoclonal antibodies in adolescents are scarce. Methods: We conducted an exploratory, retrospective cohort analysis of depersonalized routine-care data from adolescents with migraine in the German Pain e-Registry. Patients were eligible if they had at least one 6-month episode with high-evidence conventional oral preventives (HECP) and one 6-month episode with a CGRP monoclonal antibody (CGRP-mAb), each with baseline and follow-up documentation, enabling intra-individual descriptive comparisons. The primary endpoint was a pragmatic composite of 6-month treatment persistence and ≥50% reduction in monthly migraine days (MMD). Secondary outcomes included MMD, MMD with acute medication (MMDAM), migraine-related sick-leave days (MMSLD), disability (MIDAS), and patient-reported psychosocial outcomes. Results: A total of 422 adolescents contributed 1448 HECP and 422 CGRP-mAb episodes. Premature discontinuation occurred in 68.8% (HECP) and 11.9% (CGRP-mAb) of episodes; corresponding 6-month persistence was 30.6% and 88.2%, respectively. Mean MMD decreased from 11.7 to 9.4 during HECP episodes and from 11.6 to 4.4 during CGRP-mAb episodes. A ≥50% MMD reduction occurred in 25.4% (HECP) and 70.9% (CGRP-mAb) of episodes; the composite endpoint was met in 23.7% and 69.9%, respectively. CGRP-mAb episodes were associated with numerically larger improvements across secondary outcomes. Conclusions: In this high-burden adolescent cohort, CGRP-mAb treatment episodes were associated with higher persistence and broader improvements than prior conventional preventive episodes. Given the retrospective, non-randomized, sequential design, these findings are hypothesis-generating and do not constitute evidence of comparative effectiveness. Controlled pediatric trials and long-term safety studies are warranted.

This study aimed to evaluate the comparative effectiveness of propranolol therapy and structured behavioral interventions in reducing headache severity in pediatric patients and to identify predictors of treatment response. In this prospective, single-center study, 178 pediatric patients diagnosed with migraine based on the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria were enrolled. Participants were allocated into two groups according to baseline Pediatric Migraine Disability Assessment Scale (PedMIDAS) scores: Group 1 (PedMIDAS <15, n = 88) received standardized behavioral therapy, while Group 2 (PedMIDAS ≥15, n = 90) received propranolol (1-3 mg/kg/day) for 12 weeks. Primary outcomes were predefined as changes in monthly migraine attack frequency, PedMIDAS scores, and Visual Analog Scale (VAS)-measured headache intensity. Vitamin D deficiency and vitamin B12 deficiency were evaluated as biochemical predictors, and adherence was monitored bi-weekly. Both groups showed significant improvement at week 12. Monthly migraine attacks declined from 3.5 ± 1.6 to 2.1 ± 1.2 in Group 1 and from 6.4 ± 2.1 to 3.1 ± 1.7 in Group 2. PedMIDAS scores decreased from 8.60 ± 3.25 to 5.75 ± 2.52 and 24.40 ± 9.65 to 16.11 ± 7.72, respectively (p < 0.001 both). VAS scores also improved in both groups with no significant between-group difference in percentage reduction. A ≥50% reduction in attack frequency plus ≥1-grade PedMIDAS improvement defined treatment response. In the propranolol group, response was independently associated with benign paroxysmal vertigo and essential tremor, while vitamin D and vitamin B12 deficiency predicted poorer outcomes. Both propranolol and structured behavioral therapy effectively reduce migraine-related disability and pain in pediatric patients, yielding comparable proportional improvements. The identification of key clinical and biochemical predictors supports a personalized treatment approach, integrating comorbidity screening and nutritional assessment to optimize outcomes. ClinicalTrials.gov/NCT07180043, retrospectively registered.