Responder rates with eptinezumab over 24 weeks in patients with prior preventive migraine treatment failures: post hoc analysis of the DELIVER randomized clinical trial.

BACKGROUND AND PURPOSE: Eptinezumab reduced monthly migraine days more than placebo in the DELIVER study, a clinical trial with patients with difficult-to-treat migraine and prior preventive treatment failures. This post hoc analysis assesses the sustained response to eptinezumab at the population and patient level and evaluates the potential for response in initial non-responders. METHODS: Adults with chronic or episodic migraine and two to four prior preventive treatment failures were randomized to eptinezumab 100 mg, 300 mg or placebo every 12 weeks. Primary outcomes in this post hoc analysis are the proportion of patients with ≥30%, ≥50% or ≥75% reduction in monthly migraine days (i.e., migraine responder rates [MRRs]) during weeks 1-12 and weeks 13-24 and across 4-week intervals. Secondary outcomes are maintenance and shifts in MRRs from weeks 1-12 to weeks 13-24. RESULTS: Between weeks 1-12 and 13-24, ≥30% MRRs increased from 65.9% to 70.4% (100 mg) and from 71.0% to 74.5% (300 mg), versus 36.9% to 43.1% (placebo). The ≥50% and ≥75% MRRs were sustained or increased over the 24-week period. The largest increase in ≥30% MRRs occurred after the second infusion with eptinezumab. The percentage of initial non-responders (<30% MRRs during weeks 1-12) who experienced response (≥30% MRRs during weeks 13-24) to the second dose was 34.7% (100 mg) and 30.4% (300 mg) with eptinezumab versus 21.1% with placebo. CONCLUSION: Across MRR thresholds, most patients who responded to eptinezumab during weeks 1-12 maintained or improved response during weeks 13-24. More than one-third of initial non-responders became responders after their second infusion.

A real-world prospective observational study of eptinezumab in Asian patients with migraine.

OBJECTIVE: To evaluate the real-world effectiveness of eptinezumab for migraine prevention in Asian patients. BACKGROUND: Eptinezumab is a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), a potent vasodilator with an important role in migraine pathophysiology. Although there is robust clinical evidence from pivotal Phase 3 placebo-controlled trials of the efficacy of eptinezumab for migraine prevention, there are limited data on the real-world effectiveness of eptinezumab in Asian patient cohorts. METHODS: This was a non-interventional, prospective, multisite cohort study of adults with migraine (International Classification of Headache Disorders, 3rd edition criteria) in Singapore who were prescribed eptinezumab (100 mg at baseline and Month 3, administered intravenously) and were followed until Month 6. The primary endpoint was change from baseline in monthly migraine days (MMDs) at Month 3 and Month 6. Secondary endpoints were ≥30% and ≥50% responder rates, and change from baseline in the Headache Impact Test-6 (HIT-6), Migraine Disability Assessment (MIDAS), Migraine-Specific Quality of Life (MSQ), patient-identified most bothersome symptom (PI-MBS), acute medication use at Month 3 and Month 6, and safety. RESULTS: Enrolled patients (completed = 29/30) had on average 3.4 (SD 2.9) previous preventive treatments; 29/30 of the patients had trialed at least one previous preventive treatment without benefit. Most had previously trialed oral preventives (87%, 26/30) and anti-CGRP (70%, 21/30). Relative to baseline, mean MMDs decreased by 4.3 days (95% CI 2.1-6.4; p < 0.001) at Month 3 and 4.9 days (95% CI 2.1-7.7; p < 0.001) at Month 6. At Month 3 and Month 6, 14/30 (47%) and 15/29 (52%) of the patients were ≥30% responders, and 6/30 (20%) and 8/29 (28%) patients were ≥50% responders, respectively. The number of patients with severe life impairment based on the HIT-6 score (total score 60-78) decreased from 24/30 (80%) at baseline to 19/30 (63%) at Month 3 and 19/29 (66%) at Month 6. The mean MIDAS score decreased by 24.6 points (95% CI 2.82-46.38; p = 0.028) at Month 6, and the mean MSQ score increased by 12.2 points (95% CI 5.18-19.20; p = 0.001) at Month 3 and 13.6 points (95% CI 4.58-22.66; p = 0.004) at Month 6. Most patients reported improvement in the PI-MBS at Month 3 (73%, 22/30) and Month 6 (55%, 16/29). Acute medication use for headache relief decreased by 3.3 days/month (95% CI 1.0-5.6; p = 0.007) at Month 3 and 4.7 days/month (95% CI 1.7-7.7; p = 0.003) at Month 6. Treatment-emergent adverse events (TEAEs) were reported in 16/30 (54%) patients, mostly mild/moderate in severity. No serious TEAEs led to treatment discontinuation. CONCLUSION: Quarterly eptinezumab administration was effective and well-tolerated in Asian patients with chronic migraine.

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

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Eptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH.

Structural equation modeling for identifying the drivers of health-related quality of life improvement experienced by patients with migraine receiving eptinezumab.

BACKGROUND: As new migraine therapies emerge, it is crucial for measures to capture the complexities of health-related quality of life (HRQoL) improvement beyond improvements in monthly migraine day (MMD) reduction. Investigations into the correlations between MMD reduction, symptom management, and HRQoL are lacking, particularly those that focus on improvements in canonical symptoms and improvement in patient-identified most-bothersome symptoms (PI-MBS), in patients treated with eptinezumab. This exploratory analysis identified efficacy measures mediating the effect of eptinezumab on HRQoL improvements in patients with migraine. METHODS: Data from the DELIVER study of patients with 2-4 prior preventive migraine treatment failures (NCT04418765) were inputted to two structural equation models describing sources of HRQoL improvement via Migraine-Specific Quality-of-Life Questionnaire (MSQ) scores. A single latent variable was defined to represent HRQoL and describe the sources of HRQoL in DELIVER. One model included all migraine symptoms while the second model included the PI-MBS as the only migraine symptom. Mediating variables capturing different aspects of efficacy included MMDs, other canonical symptoms, and PI-MBS. RESULTS: In the first model, reductions in MMDs and other canonical symptoms accounted for 35% (standardized effect size [SES] - 0.11) and 25% (SES - 0.08) of HRQoL improvement, respectively, with 41% (SES - 0.13) of improvement comprising "direct treatment effect," i.e., unexplained by mediators. In the second model, substantial HRQoL improvement with eptinezumab (86%; SES - 0.26) is due to MMD reduction (17%; SES - 0.05) and change in PI-MBS (69%; SES - 0.21). CONCLUSIONS: Improvements in HRQoL experienced by patients treated with eptinezumab can be substantially explained by its effect on migraine frequency and PI-MBS. Therefore, in addition to MMD reduction, healthcare providers should discuss PI-MBS improvements, since this may impact HRQoL. Health technology policymakers should consider implications of these findings in economic evaluation, as they point to alternative measurement of quality-adjusted life years to capture fully treatment benefits in cost-utility analyses. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT04418765 ; EudraCT (Identifier: 2019-004497-25; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25 ).

Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study.

BACKGROUND: Despite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients' and physicians' real-world experiences with eptinezumab for chronic migraine (CM). METHODS: REVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience. RESULTS: Of the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported "good" days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses. CONCLUSION: This real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians.

An economic evaluation of eptinezumab for the preventive treatment of migraine in the UK, with consideration for natural history and work productivity.

BACKGROUND: Migraine is a highly prevalent neurological disease with a substantial societal burden due to lost productivity. From a societal perspective, we assessed the cost-effectiveness of eptinezumab for the preventive treatment of migraine. METHODS: An individual patient simulation of discrete competing events was developed to evaluate eptinezumab cost-effectiveness compared to best supportive care for adults in the United Kingdom with ≥ 4 migraine days per month and prior failure of ≥ 3 preventive migraine treatments. Individuals with sampled baseline characteristics were created to represent this population, which comprised dedicated episodic and chronic migraine subpopulations. Clinical efficacy, utility, and work productivity inputs were based on results from the DELIVER randomised controlled trial (NCT04418765). Timing of natural history events and treatment holidays-informed by the literature-were simulated to unmask any natural improvement of the disease unrelated to treatment. The primary outcomes were monthly migraine days, migraine-associated costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and net monetary benefit, each evaluated over a 5-year time horizon from 2020. Secondary analyses explored a lifetime horizon and an alternative treatment stopping rule. RESULTS: Treatment with eptinezumab resulted in an average of 0.231 QALYs gained at a saving of £4,894 over 5 years, making eptinezumab dominant over best supportive care (i.e., better health outcomes and less costly). This result was confirmed by the probabilistic analysis and all alternative assumption scenarios under the same societal perspective. Univariate testing of inputs showed net monetary benefit was most sensitive to the number of days of productivity loss, and monthly salary. CONCLUSIONS: This economic evaluation shows that from a societal perspective, eptinezumab is a cost-effective treatment in patients with ≥ 4 migraine days per month and for whom ≥ 3 other preventive migraine treatments have failed. TRIAL REGISTRATION: N/A.

Improvement of comorbid anxiety and depression in patients with migraine treated with injectable preventive calcitonin gene-related peptide antagonists: Review of clinical evidence.

Background: Migraine is often associated with depression and anxiety, leading to a diminished quality of life. Calcitonin gene-related peptide (CGRP) antagonists have shown promise in treating migraines, but their effects on concurrent depression and anxiety have not been clarified. Methods: A literature review was conducted on ClinicalTrials.gov, PubMed, Ovid Medline, and EMBASE focusing on phase 3 clinical trials, post-hoc analysis studies, and real-world evidence (RWE) published in the past 5 years. The review primarily utilized patient-reported outcome tools, such as the Patient Health Questionnaire-9, Hamilton Depression Rating Scale, Beck Depression Inventory-II, generalized anxiety disorder (GAD)-7, and Hamilton Anxiety Rating Scale (HARS), to assess anxiety and depression in relation to CGRP-targeted monoclonal antibodies. Results: Out of 260 studies, 17 met the inclusion criteria. Eptinezumab lacked sufficient evidence regarding its impact on depression and anxiety. While sufficient evidence on its effect on comorbid anxiety was not available, fremanezumab was shown to significantly improve comorbid depression in one study while not achieving statistical significance in another. Erenumab and galcanezumab showed significant improvement in comorbid depression, implying possible benefits in patients with migraine. Galcanezumab showed faster relief from depressive symptoms than other injectable CGRP antagonists. Galcanezumab also exhibited improvements in GAD-7 scores for anxiety, although not statistically significant, whereas RWE showed promising HARS scores for both galcanezumab and erenumab. Conclusions: Galcanezumab and erenumab appear to be more effective in improving concurrent depressive and anxiety symptoms in migraine patients than fremanezumab. Notably, these psychometric questionnaires were not the primary outcome measures of the trials and were not specifically designed to investigate the effects of these medications on depression or anxiety. Further research is needed to fully understand the impact of CGRP antagonists on mental health disorders associated with migraines. These findings have implications for enhancing the overall well-being and quality of life in individuals with migraines and comorbid psychiatric conditions.

Anti-CGRP mAbs for the Preventive Treatment of Migraine: An Overview Review and a Cost Saving Analysis in the Global Scenario.

Objectives: Migraine is a neurological disease with a high frequency of incidence. The new monoclonal antibodies selective for the calcitonin gene-related peptide and its ligand (anti-CGRP mAbs) have been marketed both in the USA and EU based on the positive efficacy results in the prevention of migraine. This search has been carried out with the aim of collecting real-world evidence on the effectiveness of anti-CGRP mAbs, performing a cost-savings analysis, and comparing performances among anti-CGRP mAbs medicines marketed in the American and European market. Methods: The literature review has been performed in PubMed database on 31 December 2022; the cost of the unitary dose of anti-CGRP mAbs has been extracted consulting an American national database. Results: The results confirm efficacy and good tolerability of anti-CGRP mAbs, determining a difference in the purchase price. In fact, all extracted studies showed a protective risk factor exposure in monthly migraine days reduction for all the anti-CGRP mAbs, whereas the cost analysis showed that using eptinezumab, in a quarter there is a cost saving of at least $425 per patient, compared with the other anti-CGRP mAbs. Conclusions: With equal efficacy and equal safety, anti-CGRP mAbs should be prescribed also regard to the cost established at the negotiation, making sure to guarantee the best treatment to the patients, but at the same time impacting as little as possible to the healthcare services resources.

New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy.

BACKGROUND: Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP(-R) mAbs) and small-molecule CGRP receptor antagonists (gepants) are new mechanism-based prophylactic drugs developed to address the unmet needs of pre-existing migraine prophylactic medications. However, several uncertainties remain in their real-world applications. METHODS: This is a narrative review of the literature on the use of CGRP-targeting novel therapeutics in specific situations, including non-responders to prior therapy, combination therapy, switching, and treatment termination. In the case of lack of available literature, we made suggestions based on clinical reasoning. RESULTS: High-quality evidence supports the use of all available anti-CGRP(-R) mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) in non-responders to prior therapy. There is insufficient evidence to support or reject the efficacy of combining CGRP(-R) mAbs or gepants with oral migraine prophylactic agents or botulinum toxin A. Switching from one CGRP(-R) mAb to another might benefit a fraction of patients. Currently, treatment termination depends on reimbursement policies, and the optimal mode of termination is discussed. CONCLUSIONS: New prophylactic drugs that target the CGRP pathway are promising treatment options for patients with difficult-to-treat migraine. Individualized approaches using a combination of new substances with oral prophylactic drugs or botulinum toxin A, switching between new drugs, and adjusting treatment duration could enhance excellence in practice.

Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study.

BACKGROUND: Migraine is a disabling neurological disease adversely affecting many aspects of life. Most patients are still required to have failed several older oral preventive therapies before being reimbursed for a preventive, migraine-specific anti-calcitonin gene-related peptide treatment. In the 24-week placebo-controlled portion of DELIVER, eptinezumab was shown to reduce migraine frequency and resulted in higher migraine responder rates compared with placebo in patients with two to four previous preventive treatment failures. This subgroup analysis assessed if demographic or clinical characteristics were associated with differences in preventive benefits. METHODS: Migraine frequency reductions and responder rates (i.e., the proportion of patients reaching a ≥50% and ≥75% reduction in monthly migraine days relative to baseline) were determined in the total population and predefined subgroups by sex, age, migraine frequency (chronic migraine, episodic migraine, high-frequency episodic migraine, low-frequency episodic migraine), medication overuse, medication-overuse headache, and previous preventive treatment failures (2, >2). The primary endpoint was change from baseline in monthly migraine days over weeks 1-12. RESULTS: Eptinezumab 100 and 300 mg reduced monthly migraine days more than placebo over weeks 1-12 (-4.8 and -5.3 vs -2.1, respectively; p < 0.0001). In most subgroups, eptinezumab-treated patients demonstrated larger monthly migraine days reductions from baseline over weeks 1-12 than patients receiving placebo, with reductions maintained or increased over weeks 13-24. For ≥50% and ≥75% migraine responder rates, the odds ratios versus placebo all numerically favored eptinezumab. CONCLUSION: Eptinezumab had larger monthly migraine days reductions and higher responder rates than placebo across clinically relevant subgroups showing that, across different demographic populations and clinical characteristics, eptinezumab is effective in patients with migraine and prior preventive treatment failures.Trial Registration: ClinicalTrials.gov (Identifier: NCT04418765).

Emerging drugs for the preventive treatment of migraine: a review of CGRP monoclonal antibodies and gepants trials.

INTRODUCTION: Migraine is a leading cause of years lived with disability and preventive strategies represent a mainstay to reduce health-related disability and improve quality of life of migraine patients. Until a few years ago, migraine prevention was based on drugs developed for other clinical indications and relocated in the migraine therapeutic armamentarium, characterized by unfavorable tolerability profiles. The advent of monoclonal antibodies against Calcitonin Gene-Related Peptide (CGRP) and gepants, CGRP receptor antagonists, has been a turning point in migraine prevention owing to advantageous efficacy, safety and tolerability profiles.Nevertheless, while in an ideal scenario a drug characterized by significant greater efficacy and tolerability compared to existing therapeutic strategies should be adopted as a first-line treatment, cost-effectiveness analyses available for monoclonal antibodies against CGRP pathway tend to limit their administration to more severe migraine phenotypes. AREAS COVERED: The present narrative review aims to provide a critical appraisal of phase II and III CGRP-mAbs and gepants trials to analyze their use in clinical practice. EXPERT OPINION: Despite monoclonal antibodies against CGRP pathway and gepants can be undoubtedly considered top-of-the-range treatments, there are still issues deserving to be addressed in the coming years as the risk of off-target effects as well as their economic sustainability based on the considerable migraine burden.

Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures.

BACKGROUND AND PURPOSE: In the phase 3b, randomized, double-blind, placebo-controlled DELIVER clinical trial, eptinezumab reduced migraine frequency and headache in adults with two to four prior preventive treatment failures. Here, the effect of eptinezumab on coinciding patient-reported outcomes is reported. METHODS: Adults were randomized to receive eptinezumab 100, 300 mg or placebo intravenously at weeks 12 and 24. The EQ-5D-5L, measuring overall patient health, and the six-item Headache Impact Test were completed every 4 weeks. The Patient Global Impression of Change was completed at weeks 4, 12 and 24. Patient-identified most bothersome symptom and the Migraine-Specific Quality of Life Questionnaire were administered at weeks 12 and 24. RESULTS: Eptinezumab improved patient-reported outcomes more than placebo, starting at week 4 and at all subsequent time points. By week 12, patients' overall health (EQ-5D-5L visual analog scale score) improved with eptinezumab treatment (difference from placebo in change from baseline: 100 mg, 5.1, 95% confidence interval [CI] 2.2, 8.1, p < 0.001; 300 mg, 7.5, 95% CI 4.5, 10.4, p < 0.0001). At week 12, eptinezumab improved headache-related quality of life (difference from placebo in change from baseline in Headache Impact Test total score: 100 mg, -3.8, 95% CI -5.0, -2.5, p < 0.0001; 300 mg, -5.4, 95% CI -6.7, -4.2, p < 0.0001), including each Migraine-Specific Quality of Life Questionnaire domain (p ≤ 0.0001, all comparisons). Over twice as many patients receiving eptinezumab than placebo reported much or very much improvement on the Patient Global Impression of Change and patient-identified most bothersome symptom. CONCLUSION: Patients with two to four prior preventive treatment failures receiving eptinezumab versus placebo reported greater improvements in well-being, quality of life and most bothersome symptoms compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04418765; EudraCT identifier: 2019-004497-25.

Early clinical experience with eptinezumab: results of a retrospective observational study of patient response in the United States.

BACKGROUND: The efficacy and safety of eptinezumab for preventive migraine treatment in adults have been demonstrated in multiple, large-scale clinical trials. This non-interventional, retrospective, observational chart review was conducted to examine patient response to eptinezumab 100 mg or 300 mg every 12 weeks for 6 months in the clinical setting. METHODS: Eight headache specialists who reported early clinical experience with eptinezumab enrolled the first adults (1-6 adults per clinician; age ≥ 18 years) who met predefined selection criteria (including ≥ 12-month history of migraine, ≥ 4 migraine days/month prior to eptinezumab initiation, receipt of ≥ 2 consecutive eptinezumab doses, and ≥ 12-week follow-up period), and provided detailed patient, disease, treatment, and outcome information via SurveyMonkey and standardized case-report forms. RESULTS: Charts from 31 adults (median age, 49 years) with migraine (93.6% chronic) who received eptinezumab for the preventive treatment of migraine were reviewed. Most patients (26/31 [83.9%]) were initiated at 100 mg. Eptinezumab reduced mean headache frequency (24.3 monthly headache days [MHDs] at baseline; 17.1 MHDs at Month 6); mean migraine frequency (17.3 monthly migraine days [MMDs] at baseline; 9.1 MMDs at Month 6); attack severity (17/31 [54.8%] patients); acute headache medication use (12.5 acute medication days at baseline; 7.4 at Month 6); and patient-reported disability (11/22 [50.0%] severe at baseline; 7/19 [36.8%] at Month 6). More than three-quarters of patients (24/31 [77.4%]) perceived improved disability/function and most (30/31 [96.8%]) perceived eptinezumab to be well tolerated after 6 months. Most of the headache specialists reported that eptinezumab was well tolerated by patients (30/31 [96.8%]) and that the intravenous infusion experience was not challenging. CONCLUSIONS: Patients with migraine who received 6 months of preventive treatment with eptinezumab experienced reductions in migraine and headache frequency, disability, and acute medication use during the course of treatment.

Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: For some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH. METHODS: SUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18-75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1-12 was the primary efficacy endpoint. RESULTS: Patients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1-12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints. CONCLUSION: All endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

Eptinezumab improved patient-reported outcomes in patients with migraine and medication-overuse headache: Subgroup analysis of the randomized PROMISE-2 trial.

OBJECTIVE: To evaluate the effect of eptinezumab on patient-reported outcomes in patients with chronic migraine (CM) and medication-overuse headache (MOH). BACKGROUND: MOH is a secondary headache disorder commonly occurring in patients with CM and associated with functional and psychological impairments. Medication overuse and monthly headache and migraine days were reduced with eptinezumab compared with placebo as published previously; however, these outcomes do not fully capture the burden of migraine and treatment effect. METHODS: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled trial in adults with CM. Patients were randomized (1:1:1) to receive eptinezumab 100 mg, eptinezumab 300 mg, or placebo (up to 2 doses, 12 weeks apart). Patients completed the following patient-reported outcomes: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), patient-identified most bothersome symptom (PI-MBS), and 36-item Short-Form Health Survey (SF-36). RESULTS: A total of 431 CM patients (139, 147, and 145 patients in the eptinezumab 100 mg, eptinezumab 300 mg, and placebo groups, respectively) had MOH diagnosed at screening (40.2% of the total PROMISE-2 population [n = 1072]). In CM with MOH patients, both doses of eptinezumab were associated with clinically meaningful improvements in mean HIT-6 total scores by week 4 and remained improved throughout the 24-week study. Responder rates for individual HIT-6 items were greater with eptinezumab than with placebo at all time points. At week 12, almost twice as many eptinezumab-treated patients indicated the PGIC was "much" or "very much" improved (58.5% [79/135, 100 mg] and 67.4% [95/147, 300 mg] vs. 35.8% [48/134, placebo]). Patients in the eptinezumab groups showed numerically greater improvements over placebo in the PI-MBS and SF-36 scores. CONCLUSIONS: This subgroup analysis in patients with CM/MOH at baseline suggests that eptinezumab treatment is associated with early, sustained, and clinically meaningful improvements in patient-reported outcomes.

Persistence to anti-CGRP monoclonal antibodies and onabotulinumtoxinA among patients with migraine: a retrospective cohort study.

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA. METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same drug (anti-CGRP mAb or onabotulinumtoxinA) without a ≥ 15-day gap in medication supply on/after June 25, 2020, to December 31, 2021. Patients were indexed at the start of their most recent episode. Patients were considered non-persistent and discontinued the therapy associated with their most recent episode if there was ≥ 15-day gap in medication supply. A Cox proportional-hazards model estimated the discontinuation hazard between treatments. The gap periods and cohort definition were varied in sensitivity analyses. RESULTS: The study included 66,576 patients (median age 46 years, 88.6% female). More eptinezumab-treated patients had chronic migraine (727/1074), ≥ 3 previous acute (323/1074) or preventive (333/1074) therapies, and more prior treatment episodes (3) than other treatment groups. Based on a 15-day treatment gap, patients on subcutaneous anti-CGRP mAbs had a 32% (95% CI: 1.19, 1.49; erenumab), 42% (95% CI: 1.27, 1.61; galcanezumab), and 58% (95% CI: 1.42, 1.80; fremanezumab) higher discontinuation hazard than those receiving eptinezumab, with this relationship attenuated, but still statistically significant based on 30-day and 60-day treatment gaps. There was no significant difference in the discontinuation hazard between eptinezumab and onabotulinumtoxinA. Based on a 15-day treatment gap among patients who newly initiated therapy, the discontinuation hazard of subcutaneous anti-CGRP mAbs remained significantly higher compared to eptinezumab and onabotulinumtoxinA. CONCLUSION: Patients treated with eptinezumab demonstrated persistency that was higher than subcutaneous anti-CGRP mAbs and similar to onabotulinumtoxinA.

Efficacy and safety of eptinezumab for migraine: A systematic review and meta-analysis.

Background: Calcitonin gene-related peptides (CGRP) have been considered a new effective means to prevent and treat migraine. Eptinezumab is a new class of CGRP antagonists that has been ratified for clinical treatment. The purpose of this systematic review was to assess and contrast the therapeutic effect and safety of eptinezumab in the management of migraine in comparison with a placebo. Materials and Methods: We systematically searched PubMed, Embase, Cochrane Library, and the US National Institutes of Health Clinical Trials Registry from the earliest date to February 16, 2023, for randomized controlled trials (RCTs). The mean difference (MD) and risk ratio (RR) were chosen to assess clinical indicators. Results: In total, there were 2, 739 patients in four RCTs, who were ultimately included. Our summarized results showed that eptinezumab had better healing efficacy compared to placebo with respect to monthly migraine days (MD = -1.56, 95% confidence interval [CI]: -2.32, -0.79, P < 0.001), improving ≥75% migraine responder rate (RR = 1.80, 95% CI: 1.40, 2.33, P < 0.001), ≥50% migraine responder rate (RR = 1.46, 95% CI: 1.33, 1.61, P < 0.001), and 100% migraine responder rate (RR = 2.41, 95% CI: 1.08, 5.38, P < 0.001). Furthermore, compared with placebo, there was no significant increase for treatment-related adverse events (RR = 1.01, 95% CI 0.94, 1.10, P = 0.71) and serious AEs (RR = 0.93, 95% CI 0.46, 1.90, P = 0.84). It was found that all dosages except for 10 mg had significant efficacy compared with placebo, especially 300 mg (P < 0.001). Conclusion: Eptinezumab has good healing efficacy and insignificant adverse effects in treating migraine, particularly the dosage of 300 mg.

Reduction in migraine-associated burden after eptinezumab treatment in patients with chronic migraine.

OBJECTIVE: To examine changes in the occurrence, severity, and symptoms of headache episodes in patients with chronic migraine following eptinezumab treatment. METHODS: PROMISE-2 was a double-blind, placebo-controlled, parallel-group trial that randomized adults with chronic migraine to eptinezumab 100 mg, 300 mg, or placebo IV every 12 weeks for up to 24 weeks (2 infusions). Headache episodes (migraine and non-migraine) and their characteristics were reported in daily electronic diaries during the 28-day baseline and throughout the 24-week treatment period. RESULTS: A total of 1072 patients were included in this post hoc analysis. Mean monthly headache days decreased by 8.9 (100 mg) and 9.7 (300 mg) compared to a 7.3 decrease in placebo over the first 4-week interval post initial dose and reductions were maintained throughout the 24-week treatment period. Mean monthly headache episodes also decreased by 8.4 (100 mg) and 9.0 (300 mg) compared to a decrease of 7.1 with placebo. The proportion of headache episodes that were migraine attacks decreased by 11.2% (100 mg), 12.4% (300 mg), and 3.9% (placebo), and among remaining headaches decreases in severe pain, nausea, phonophobia, photophobia, and physical activity limitations were numerically greater than placebo. CONCLUSIONS: Patients with chronic migraine treated with eptinezumab decreased the monthly severity and frequency of headache days and episodes more than placebo. Beyond decreased headache frequency, patients treated with eptinezumab reported a reduction in the percent of remaining headache episodes that were migraine attacks, as well as a decrease in burdensome symptoms of headache episodes, indicating additional decreased headache severity after eptinezumab treatment.Trial registration: ClinicalTrials.gov Identifier: NCT02974153; registered November 23, 2016.

Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2.

BACKGROUND: This post hoc subgroup analysis evaluated the efficacy and safety of eptinezumab for migraine prevention in patients with migraine and self-reported aura. METHODS: PROMISE-1 (NCT02559895; episodic migraine) and PROMISE-2 (NCT02974153; chronic migraine) were randomized, double-blind, placebo-controlled trials that evaluated eptinezumab for migraine prevention. In both studies, the primary outcome was the mean change from baseline in monthly migraine days over Weeks 1-12. Patients in this analysis included those who self-reported migraine with aura at screening. RESULTS: Of patients with episodic migraine, ∼75% reported a history of aura at screening; of patients with chronic migraine, ∼35% reported a history of aura. Changes in monthly migraine days over Weeks 1-12 were -4.0 (100 mg) and -4.2 (300 mg) with eptinezumab versus -3.1 with placebo in patients with episodic migraine with aura, and were -7.1 (100 mg) and -7.6 (300 mg) with eptinezumab versus -6.0 with placebo in patients with chronic migraine with aura. Treatment-emergent adverse events were reported by 56.0% (100 mg), 57.4% (300 mg), and 55.4% (placebo) of patients. CONCLUSIONS: The preventive migraine efficacy of eptinezumab in patients in the PROMISE studies who self-reported aura was comparable to the overall study populations, demonstrating a similarly favorable safety and tolerability profile.Trial registration: ClinicalTrials.gov Identifiers: NCT02559895 and NCT02974153.

Shift in diagnostic classification of migraine after initiation of preventive treatment with eptinezumab: post hoc analysis of the PROMISE studies.

BACKGROUND: Monthly headache frequency directly correlates with personal/societal burden and impacts severity and preventive treatment decisions. This post hoc analysis identified shifts from higher to lower frequency headache categories over 6 months in patients with migraine participating in the PROMISE clinical trials receiving two eptinezumab doses. METHODS: Headache frequency at baseline and over study months 1-6 was categorized into 4 groups: chronic migraine (CM; ≥ 15 monthly headache days [MHDs]), high-frequency episodic migraine (HFEM; 10-14 MHDs), low-frequency episodic migraine (LFEM; 4-9 MHDs), and ≤ 3 MHDs. Outcomes included the percentage of patients within each MHD category, the percentage of patients improving by ≥ 1 MHD category, and the number of months with reduction of ≥ 1 MHD category. Data from patients who received approved eptinezumab doses (100 mg or 300 mg) or placebo were included. RESULTS: Mean headache frequency at baseline in PROMISE-1 was 10 MHDs; most patients were classified as having HFEM (48.6%) or LFEM (43.9%). At Month 1, 62/221 (28.1%), 75/222 (33.8%), and 45/222 (20.3%) patients who received eptinezumab 100 mg, 300 mg, and placebo had ≤ 3 MHDs, with 97/221 (43.9%), 108/222 (48.6%), and 84/222 (37.8%), respectively, falling below the diagnostic EM threshold at Month 6. More than one-third (79/221 [35.7%], 83/222 [37.4%], and 68/222 [30.6%] of patients in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively), had 6 months of reduction of ≥ 1 frequency category. At baseline in PROMISE-2, mean headache frequency was 20.5 MHDs. All patients (100%) in the eptinezumab 100 mg and placebo groups had CM, as did 99.4% of patients receiving eptinezumab 300 mg. At Month 1, 209/356 (58.7%), 216/350 (61.7%), and 167/366 (45.6%) patients treated with eptinezumab 100 mg, 300 mg, and placebo had ≤ 14 MHDs, with 240/356 (67.4%), 249/350 (71.1%), and 221/366 (60.4%), respectively, falling below CM threshold at Month 6. Additionally, 153/356 (43.0%), 169/350 (48.3%), and 116/366 (31.7%) patients in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, had 6 months of reduction of ≥ 1 frequency category. CONCLUSION: In the PROMISE studies, episodic and chronic migraine patients treated with eptinezumab were more likely to reduce their headache frequency versus placebo, which directly and in a sustained way improved their diagnostic category classification. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02559895, NCT02974153.