Gene-related Peptide Monoclonal Antibodies Research Articles

Long-term effectiveness of eptinezumab in the treatment of patients with chronic migraine and medication-overuse headache.

This post hoc analysis of the PREVAIL study explored the effectiveness of eptinezumab for up to 2 years of open-label treatment in the subgroup of patients with chronic migraine who had a confirmed diagnosis of medication-overuse headache (MOH) at screening. MOH is a disabling and costly secondary headache disorder characterized by increased headache frequency and/or severity with increased acute headache medication use. Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduces headache frequency, severity, and associated disability and improves functioning and health-related quality of life as a preventive migraine therapy; short-term benefits in patients with concurrent MOH have also been reported. Participants received up to eight quarterly intravenous infusions of eptinezumab 300 mg in the phase 3, single-arm, open-label PREVAIL study. Safety and patient-reported outcome measures (Migraine Disability Assessment [MIDAS], 6-item Headache Impact Test [HIT-6], patient-identified most bothersome symptom [PI-MBS], Patient Global Impression of Change [PGIC], and 36-item Short-Form Health Survey [SF-36]) were conducted at predefined intervals. Patients were observed up to 20 weeks after their last infusion (Week 104). A total of 49/128 (38.3%) patients enrolled in PREVAIL had an MOH diagnosis at screening. In the MOH subgroup, long-term eptinezumab treatment was associated with reductions in headache frequency (43/49 [87.8%] patients reported ≥50% reduction in MIDAS-derived headache days at ≥1 visit), severity (2.2-point reduction [on a 10-point scale]), disability (mean MIDAS total score reduction of 51.9 points), and impact (mean HIT-6 total score reduction of 9.7 points) at Week 104. Most patients described a "much improved" or "very much improved" status by Week 48 (PI-MBS, 31/46 [67.4%]) and Week 104 (PGIC, 31/36 [86.1%]). Health-related quality of life improvements in the SF-36 were also observed. Eptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

The Effect of Calcitonin Gene-Related Peptide Monoclonal Antibodies on Quality of Life among Migraine Patients: Pilot Study at the Hospital of Lithuanian University of Health Sciences Kaunas Clinics.

Migraine has a negative impact on patients' quality of life, with the frequency of attacks being associated with greater disability and poorer health status. Frequent migraine-type headaches require prophylactic treatment, which has so far been of limited effectiveness until advent of calcitonin gene-related peptide (CGRP) monoclonal antibody. A prospective analysis was conducted of data from 41 migraine patients who experienced 4 or more monthly migraine days (MMD) longer than three months. At the beginning of the study, treatment with monoclonal antibodies against CGRP (fremanezumab 225 mg or erenumab 70 or 140 g per month) was prescribed according to the indications. The effect of the medications was evaluated after 3-month period. The mean age of patients was 37.17 (±11.78) years. It was found that 17 patients (41.5%) had episodic migraine (EM) and 24 (58.5%) had chronic migraine (CM). Fremanezumab was prescribed to 26 patients (63.4%) and erenumab to 15 patients (36.6%); among the latter, 13 patients used 70 mg/month and 2 patients used 140 mg/month. Three months after treatment, CM changed to EM for 19 patients (79.2%), 27 patients (65.9%) had ≥50% reduction in the number of MMD and total migraine disability assessment (MIDAS) score was reduced by >50% in 31 patients (75.6%). Also, all areas of quality of life of patients were improved after 3 months continued treatment compared to baseline. For more than half the patients using fremanezumab or erenumab after 3-month period, MMD decreased by ≥50% and total MIDAS score by >50 points. All areas of quality of life were improved after prophylactic treatment of migraine.

Anti-CGRP monoclonal antibodies improve cognitive function in patients affected by chronic migraine complicated with medication overuse-headache

Background: Migraine represents one of the most disabling neurological diseases in the world. This burden is primarily due to recurrent pain episodes, alongside cognitive function impairments that patients may experience. This paper aims to explore the effect of three anti-calcitonin Gene-Related Peptide (CGRP) monoclonal antibodies (mAbs) – erenumab, fremanezumab, and galcanezumab – on the cognitive performance of a sample of patients suffering from migraine using the Montreal Cognitive Assessment (MoCA) questionnaire.Methods: A total of 215 patients suffering from migraine who visited the Modena Headache Center were enrolled. The MoCA questionnaire was filled in by the patients at the baseline and subsequent assessments were conducted at 6 and 12 months thereafter. Additionally, patients were requested to complete the 6-item Headache Impact Test, Migraine Disability Assessment Score, and Hospital Anxiety and Depression Scale every three months.Results: The sample was composed of 82% of female participants and 87% of the enrolled patients were diagnosed with chronic migraine. Following one year of treatment, there was a significant enhancement observed in MoCA scores compared to baseline measurements. Moreover, higher consumption of analgesics, elevated body mass index (BMI), and prolonged chronic migraine history exhibited an inverse correlation with MoCA score improvements after 12 months.Conclusions: Erenumab, fremanezumab, and galcanezumab have proven to be effective in relieving the cognitive impairment associated with migraine after 1 year of treatment. These findings underscore the reversibility of cognitive impairment among migraine sufferers, even among those suffering from chronic migraine, as delineated by the majority of the patients under study. This study revealed that prolonged chronic migraine history, higher baseline analgesic intake, and elevated BMI were all predictive of diminished cognitive enhancements following treatment.

Prospective evaluation of aura during anti-calcitonin gene-related peptide monoclonal antibody therapy after 52 weeks of treatment

Background: Clinical studies have shown the efficacy and safety of monoclonal antibodies (mAbs) against calcitonin gene-related peptide (anti- CGRP) in migraine patients with and without aura. Early evidence from post hoc and small subgroup analyses suggests that anti-CGRP mAbs reduce the frequency and intensity of aura. Herein, we prospectively assessed the changes in aura after 12 months of anti-CGRP mAb treatment and performed a literature review.Methods: All outpatients treated with anti-CGRP mAbs for one year in two tertiary Headache Centers and who experienced ≥1 episode of aura/month were enrolled. The study reports data from one month before (baseline) and the last three months (months 10, 11, 12) of treatment.Results: Data from 13 patients with a diagnosis of migraine with and without aura were collected. The mean duration from aura onset was 17.8±7.9 years. At baseline nine patients (69.2%) reported visual aura, and four (30.8%) visual and sensory aura. Mean duration of aura episodes was of 34.2±15.7 minutes. At baseline, the mean number of monthly migraine days (MMDs) was 22.3±7.5, and the mean number of MMDs preceded by aura was 9.15±9.0. At month 12 of treatment, there was a significant reduction of MMDs (6.2±9.0, p=0.002) and MMDs with aura (2.6±2.7, p=0.015). Three patients reported episodes of aura without subsequent headache, a phenomenon that was absent prior to treatment. We identified 14 studies that reported changes in aura during anti-CGRP mAbs treatment.Conclusions: This prospective study shows that anti-CGRP mAbs reduce the number of migraine attacks with aura consistently with the reduction of MMDs. Randomized studies with anti-CGRP mAbs specifically assessing migraine aura are required.

Use of Calcitonin Gene-Related Peptide Monoclonal Antibodies for the Treatment of Migraines in Individuals With Multiple Sclerosis.

Migraines are a common comorbidity and source of disability in patients with chronic inflammatory diseases like multiple sclerosis (MS). Recently, therapeutic agents for episodic and chronic migraine known as calcitonin gene-related peptide (CGRP) inhibitors have shown to effectively control migraine attacks and improve quality of life in the general population. This study explored the use of these novel agents in individuals with comorbid MS. This was a retrospective, population-based cohort study at the University of South Florida's neurology clinic; it evaluated individuals with both MS and migraine. A total of 27 individuals with MS and chronic or episodic migraine who received treatment with a CGRP monoclonal antibody were identified. Of these, 63% reported a reduction in their migraine frequency of greater than 75%. Concurrent use of a disease-modifying therapy (DMT) for MS occurred in 82% of patients, and in 37% of these, the DMT used was also a monoclonal antibody. Adverse effects from CGRP monoclonal antibodies were mild and occurred in only 11% of patients, and no patient experienced worsening of their MS symptoms during cotreatment over the duration of the study. Our study showed a significant reduction in migraine frequency and a favorable adverse event profile for individuals with comorbid MS who took CGRP monoclonal antibodies and experienced no worsening of MS symptoms. In individuals with MS, CGRP monoclonal antibodies seem to be a safe and effective therapy for episodic or chronic migraine.

Update on Cluster Headaches: From Genetic to Novel Therapeutic Approaches

Cluster headaches affect 0.1% of the population and are four times more common in males than in females. Patients with this condition present with severe unilateral head pain localized in the frontotemporal lobe, accompanied by ipsilateral lacrimation, conjunctival injection, nasal congestion, diaphoresis, miosis, and eyelid edema. Recently, the first genome-wide association study of cluster headaches was conducted with the goal of aggregating data for meta-analyses, identifying genetic risk variants, and gaining biological insights. Although little is known about the pathophysiology of cluster headaches, the trigeminovascular and trigeminal autonomic reflexes and hypothalamic pathways are involved. Among anti-calcitonin gene-related peptide monoclonal antibodies, galcanezumab has been reported to be effective in preventing episodic cluster headaches.

Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: Asystematic review and meta-analysis of randomized controlled trials.

To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). Insurers mandate step therapy with NOEPs before approving CGRP mAbs. Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days. Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]). There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.

Benefit-Risk Assessment Based on Number Needed to Treat and Number Needed to Harm: Atogepant vs Calcitonin Gene–Related Peptide Monoclonal Antibodies (P5-12.007)

Benefit-Risk Assessment Based on Number Needed to Treat and Number Needed to Harm: Atogepant vs Calcitonin Gene–Related Peptide Monoclonal Antibodies (P5-12.007)

Characteristics of Patients Receiving Co-prescriptions for a Calcitonin Gene-related Peptide Monoclonal Antibody and a Gepant: A Retrospective, Observational Study (P8-12.003)

Characteristics of Patients Receiving Co-prescriptions for a Calcitonin Gene-related Peptide Monoclonal Antibody and a Gepant: A Retrospective, Observational Study (P8-12.003)

Understanding Patients’ Journeys Prior to Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention in the United States (P8-12.008)

Understanding Patients’ Journeys Prior to Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention in the United States (P8-12.008)

Interictal Burden Before Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention (P9-12.003)

Interictal Burden Before Initiating Calcitonin Gene-related Peptide Monoclonal Antibody for Migraine Prevention (P9-12.003)

Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.

Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology. The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study. The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41-61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39-57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (n = 229) and dual-therapy groups. The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30-30) to 15 (12-30) [p < 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12-30) to 8 (3-22) [p < 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25-30) to 15 (8-25) from onabot monotherapy and decreased from 25 (15-30) to 12 (4-25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (p < 0.0001). Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action.

Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop

Background Chronic migraine is a disabling condition that can substantially impact on quality of life. People with chronic migraine have headaches on at least 15 days of every month. Preventative medications aiming to reduce number of days with migraine are available, but high-quality randomised evidence is lacking for many drugs, and it is unclear which medications should be prioritised for research. There is also no existing evidence about patient and clinicians’ priorities for research. Methods We undertook a consensus workshop with patient and healthcare professional stakeholders, using nominal group technique, to understand these stakeholders’ priorities for future randomised controlled trials. We reached a consensus on a set of research recommendations for the field. Results Eight people with chronic migraine and eleven healthcare professionals took part in an online workshop. Comparisons of calcitonin gene-related peptide monoclonal antibodies (CGRP MAbs) and OnabotulinumtoxinA (BTA) were a top priority for our group. Candesartan and Flunarizine were the top drugs the group wanted to compare against placebo. Conclusions These research recommendations should guide researchers in the field, and funders when prioritising commissioned research and assessing funding applications. Particular areas to explore further are Candesartan or Flunarizine versus placebo, and comparing and combining CGRP MAbs with other medications.

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland

ObjectivesCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. MethodsData were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. ResultsBetween September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. ConclusionsThis study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review

BackgroundMigraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that...

CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society

BackgroundAnti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown.MethodsWe conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use.ResultsOf the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%).ConclusionsMost of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

Anti-calcitonin Gene-Related Peptide Monoclonal Antibodies in Migraine: Focus on Clinical Pharmacokinetics.

The calcitonin gene-related peptide transmission was the target for recent development of drugs that effectively prevent attacks of both episodic and chronic migraine. The aim of this narrative review was to offer deeper insight into pharmacokinetics of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering periods 1966-2023 and 2006-2023, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering the period 2000-2023. The monoclonal antibodies from this group are distributed mainly in the plasma and part of the extracellular space; they are neither metabolized in the liver nor excreted via the kidneys. The elimination of galcanezumab, eptinezumab and fremanezumab takes place only by a non-specific linear process via the reticuloendothelial system in the liver, while erenumab is eliminated by a non-specific process and by a specific, saturable process because of binding to receptors located on the cell membrane. Since the elimination processes do not have a large capacity, the half-life is about 2 weeks for erenumab and about 4 weeks for other monoclonal antibodies. Variability in the pharmacokinetics of these monoclonal antibodies is small in different subpopulations, and body weight is the only parameter to consider when choosing the dose of these drugs.

Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in Migraine: Focus on Drug Interactions.

Calcitonin gene-related peptide neurotransmission was the target for recent development of monoclonal antibodies that effectively prevent attacks of both episodic and chronic migraine. The aim of this narrative review was to offer deeper insight into drug-drug, drug-food and drug-disease interactions of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering the 1966-2023 and 2006-2023 periods, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering 2000-2023. Monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab) augment prophylactic action of gepants and onabotulinumtoxin A and somewhat increase efficacy of triptans used to abort migraine attacks; however, their adverse reactions may also be augmented. Pharmacokinetic interactions and interactions in general with drugs used for other indications except migraine are negligible, as are drug-food interactions. However, monoclonal antibodies may worsen diseases with already weakened CGRP neurotransmission, Raynaud phenomenon and constipation. Monoclonal antibodies used for prevention of migraine do not engage in significant pharmacokinetic interactions with other drugs; however, they do engage in pharmacodynamic interactions with other anti-migraine drugs, additively augmenting their prophylactic action, but also increasing frequency and severity of adverse reactions, which are a consequence of the CGRP neurotransmission interruption.

Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.

Women show increased prevalence and severity of migraine compared to men. Whether small molecule calcitonin gene-related peptide receptor (CGRP-R) antagonists (i.e., gepants) and monoclonal antibodies targeting either the CGRP-R or the CGRP peptide might show sexually dimorphic outcomes for acute and preventive therapy has not been established. We conducted a subpopulation analysis of available published data from FDA reviews to evaluate potential sex differences in the response rates of ubrogepant, rimegepant and zavegepant for acute migraine therapy. Available data from FDA reviews of erenumab, fremanezumab, galcanezumab and eptinezumab, approved CGRP-R and CGRP monoclonal antibodies and of atogepant were examined for prevention outcomes based on patient sex. Preventive outcomes were analyzed separately for patients with episodic migraine and chronic migraine. In women, the three approved gepants produced statistically significant drug effects regardless of dose tested on the FDA mandated co-primary endpoints, the proportion of patients achieving two-hour pain-freedom and the proportion of patients free of their most bothersome symptom at two hours post-dose. In women, the average placebo-subtracted two-hour pain-freedom proportion was 9.5% (CI: 7.4 to 11.6) and the average numbers needed to treat was 11. The free from most bothersome symptom at two hours outcomes were also significant in women. The gepant drugs did not reach statistically significant effects on the two-hour pain-freedom endpoint in the men, with an average drug effect of 2.8% (CI: -2.5 to 8.2) and an average number needed to treat of 36. For freedom from most bothersome symptom at two hours post-dose endpoint, differences were not significant in male patients. The treatment effect in each of the gepant studies was always numerically greater in women than in men. In evaluation of prevention outcomes with the antibodies or atogepant using the change from the specified primary endpoint (e.g., monthly migraine days), the observed treatment effect for episodic migraine patients almost always favored drug over placebo in both women and men. For chronic migraine patients the treatment effects of antibodies were similar in men and women and always favored the drug treated group.Conclusion/Interpretation: Small molecule CGRP-R antagonists are effective in acute migraine therapy in women but available data do not demonstrate effectiveness in men. CGRP-targeting therapies are effective for migraine prevention in both male and female episodic migraine patients but possible sex differences remain uncertain. In male and female chronic migraine patients, CGRP/CGRP-R antibodies were similarly effective. The data highlight possible differential effects of CGRP targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women.