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We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)—a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)—in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9–12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (−16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (−3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs. [ABSTRACT FROM AUTHOR]

Abstract 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. Graphical Abstract

Objectives: While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC. Methods: In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12. The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at the first month of treatment discontinuation after the second TrC (D2) compared to the first TrC (D1). Secondary endpoints included variations in monthly analgesic medications (MAM), Numeric Rating Scale (NRS), and Headache Impact Test (HIT-6) scores, ≥ 50%, ≥ 75%, and 100% response rates, and relapse from episodic migraine to CM and from no-medication overuse (MO) to MO at D2 vs. D1. Results: One-hundred-seventy-eight patients completed two 12-month TrCs with anti-CGRP mAbs. At D2, patients experienced a significant reduction in MMD (– 0.6, p = 0.028), MHD (– 2.6, p < 0.001), monthly analgesic medications (– 2.0, p < 0.001), and HIT-6 score (– 2.2, p < 0.001) compared to D1, indicating improved effectiveness. The ≥ 50% response rate at weeks 45–48 during the first TrC was 95.5%, while at weeks 45–48 of the second TrC was 99.4%. Corresponding rates at D1 was 20.2% whereas at D2 was 51.6% (p < 0.0001). No statistical difference emerged in ≥ 75% and 100% responders. The relapse rate from episodic migraine to CM at D2 was lower than at D1 (12.3% vs 30.4%; p = 0.0002) Fewer patients experienced relapse from no-MO to MO at D2 compared to D1 (29.5% vs 68.7%; p = 0.00001). Discussion: A second TrC with anti-CGRP mAbs demonstrated clinical improvements compared to the first one, as indicated by a milder migraine relapse at D2 compared to D1. Multiple TrCs with anti-CGRP mAbs could progressively modify migraine evolution by reducing CGRP-dependent neuroinflammatory nociceptive inputs to the brain. [ABSTRACT FROM AUTHOR]

Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). Methods: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. Results: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain—either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)—a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). Conclusion: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2–3 months of treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options. Methods Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort. Results In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities. Conclusions This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described.

Background: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options. Methods: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort. Results: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities. Conclusions: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described. [ABSTRACT FROM AUTHOR]

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Background: Few studies compare the clinical effectiveness of the three anti-CGRP mAbs. Moreover, no studies compare their efficacy during suspension and reprisal. Our study aimed to compare the efficacy of migraine frequency, intensity, and symptomatic medication intake during the first year of therapy, a 1-month suspension period, and a 3-month drug reprisal. Methods: A total of 160 migraineurs (chronic and high-frequency episodic) were treated with anti-CGRP mAbs (49 with fremanezumab, 55 with erenumab, and 55 with galcanezumab) for 12 months. They discontinued the therapy for 1 month and then reprised the therapy. In the three groups, we analyzed and compared the migraine days per month, migraine intensity, and symptomatic medication intake per month at baseline, 3-month, 6-month, and 12-month follow-up. We also compared these variables during the 1-month suspension and 3 months after the reprisal of the therapy. We compared the data and evaluated the response rate (>50% reduction in migraine days per month) at different follow-ups. This comparison was also performed separately for chronic and high-frequency episodic migraineurs. Results: There was no statistical difference in monthly migraine days, intensity, or symptomatic medication intake per month at the different follow-ups. Moreover, there was no difference in the response rate overall. However, in chronic migraineurs treated with galcanezumab, the response rate was higher during the 1-month suspension when compared to fremanezumab and erenumab. In high-frequency episodic migraineurs, fremanezumab had a higher response rate at 12-month follow-up when compared to galcanezumab and erenumab. Conclusions: In our study, the three anti-CGRP mAbs presented a similar response, with no significant differences, during the first year of therapy, the suspension period, and 3 months after the drug reprisal. The response rate during the 1-month suspension period in chronic migraineurs may be higher with galcanezumab. [ABSTRACT FROM AUTHOR]

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)—a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)—in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9–12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates. The safety analysis involved 44 subjects; the effectiveness analysis included 26 individuals. Eptinezumab was well-tolerated. In CM patients, eptinezumab significantly reduced MHD (−16.1 ± 9.9, p < 0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. In HFEM patients, it significantly reduced NRS, HIT-6, MIDAS, and MIBS-4, though reductions in MMD (−3.3 ± 4.5) and MAI were not statistically significant. Overall, ≥50% and ≥75% response rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). The clinical change was rated as much or very much improved by 61.0% of the patients. Eptinezumab demonstrated high effectiveness, safety, and tolerability in real-life among hard-to-treat migraine patients with multiple treatment failures, including anti-CGRP mAbs.

Background: Few studies compare the clinical effectiveness of the three anti-CGRP mAbs. Moreover, no studies compare their efficacy during suspension and reprisal. Our study aimed to compare the efficacy of migraine frequency, intensity, and symptomatic medication intake during the first year of therapy, a 1-month suspension period, and a 3-month drug reprisal. Methods: A total of 160 migraineurs (chronic and high-frequency episodic) were treated with anti-CGRP mAbs (49 with fremanezumab, 55 with erenumab, and 55 with galcanezumab) for 12 months. They discontinued the therapy for 1 month and then reprised the therapy. In the three groups, we analyzed and compared the migraine days per month, migraine intensity, and symptomatic medication intake per month at baseline, 3-month, 6-month, and 12-month follow-up. We also compared these variables during the 1-month suspension and 3 months after the reprisal of the therapy. We compared the data and evaluated the response rate (>50% reduction in migraine days per month) at different follow-ups. This comparison was also performed separately for chronic and high-frequency episodic migraineurs. Results: There was no statistical difference in monthly migraine days, intensity, or symptomatic medication intake per month at the different follow-ups. Moreover, there was no difference in the response rate overall. However, in chronic migraineurs treated with galcanezumab, the response rate was higher during the 1-month suspension when compared to fremanezumab and erenumab. In high-frequency episodic migraineurs, fremanezumab had a higher response rate at 12-month follow-up when compared to galcanezumab and erenumab. Conclusions: In our study, the three anti-CGRP mAbs presented a similar response, with no significant differences, during the first year of therapy, the suspension period, and 3 months after the drug reprisal. The response rate during the 1-month suspension period in chronic migraineurs may be higher with galcanezumab.

Currently, studies have shown that anti-CGRP monoclonal antibodies are effective drugs for the prophylaxis and treatment of episodic migraine. Therefore, for the first time, we classified and concluded 10 treatment regimens according to the different doses, drugs, routes of administration, and courses of treatment, so as to provide a reference for further clinical studies. We studied relevant randomized controlled trials (RCTs) published before August 2020 on PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials. Eleven RCTs involving 6397 patients were included in our analysis. Network meta-analysis results suggested that in the comparison of the average migraine days per month, Erenumab (140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) were superior to placebo, Erenumab(7 mg), and the difference was statistically significant; Fremanezumab (225 mg, 675 mg) was superior to Erenumab (21 mg, 70 mg), and the difference was statistically significant; in the comparison of average medication days of acute migraine-specific drug per month, Erenumab (70 mg, 140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) was superior to placebo, and Erenumab (140 mg) and Galcanezumab (120 mg, 240 mg) were superior to Erenumab (70 mg), and the difference was statistically significant; there was no statistically significant difference in the average migraine days in the last month or in the medication days of acute migraine-specific drug. Fremanezumab (225 mg) and Galcanezumab (120 mg) may be the best clinical protocol after a comprehensive assessment. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is the most common neurological disorder and represents the first cause of disability in under 50s in both genders. Available preventive drugs were primarily developed for indications other than migraine and with an unclear mechanism of action in migraine pathophysiology. Areas covered: This article reviews current preventive treatments and their shortcomings and the road that, through the understanding of calcitonin gene-related peptide (CGRP) role in migraine pathophysiology, carried to the approval of the 3 first-in-class monoclonal antibodies (mAbs) acting on the CGRP pathway. Data from phase 2 and phase 3 clinical trials of erenumab, galcanezumab and fremanezumab, both for episodic and chronic migraine prevention, are consistent for safety and efficacy. Expert opinion: Anti-calcitonin gene-related peptide mAbs have potential advantages over conventional treatments such as ease of use, quick onset of action, persistent efficacy, placebo-like safety profile and absence of pharmacological interactions. Pharmacoeconomic studies should evaluate the economic impact of these drugs taking into account the overall direct and indirect costs related to untreated migraine and to migraine treated with the other available preventive therapies. Given the high cost of these therapies, it is essential to implement all possible strategies to optimize their effectiveness by optimization of patients' selection. [ABSTRACT FROM AUTHOR]

Background & Objective: To conduct a systematic review and network meta-analysis of all randomized trials investigating effects of anti-calcitonin gene related peptide monoclonal antibodies (anti-CGRP mAbs) on adult patients with chronic migraine., Methods: MEDLINE, Embase and Cochrane Central Register of Controlled Trials searched from inception to July 2020; and clinical trial registries. The network meta-analysis was conducted in Bayesian framework using OpenBUGS and R, with the random effects model selected to allow for apparent heterogeneity between studies in the treatment comparison effects., Results: Overall 38 studies (5164 chronic migraineurs in seven randomized trials) were included with treatment course of at least 12 weeks. Fremanezumab 675 + 225 + 225 mg QM (SC) injections were numerically more effective in lowering migraine days with lower MDs compared to eptinezumab 10 mg (IV) (MD: -1.52, 95% CrIs: -4.24, 0.99), eptinezumab 30 mg (IV) (MD: -0.33, 95% CrIs: -3.02, 2.16), eptinezumab 100 mg (IV) (MD: -0.59, 95% CrIs: -2.80, 1.42), eptinezumab 300 mg (IV) (MD: -0.02, 95% CrIs: -2.29, 1.98), erenumab 70 mg QM (SC) (MD: -0.17, 95% CrIs: -2.84, 2.25), erenumab 140 mg QM (SC) (MD: -0.18, 95% CrIs: -2.87, 2.26), fremanezumab 675 mg (SC) (MD: -0.30, 95% CrIs: -1.81, 1.14), galcanezumab 120 mg QM (SC) (MD: -0.71, 95% CrIs: -3.44, 1.55) and galcanezumab 240 mg QM (SC) (MD: -0.58, 95% CrIs: -3.09, 1.89), however the results were non-significant. Similarly, the anti-CGRP mAbs were also observed to have comparable safety and immunogenicity with no significant differences., Conclusions: Although all doses of anti-CGRP mAbs have comparable efficacy, safety and tolerability based on uncertainties in indirect comparisons for all outcomes, the calculated effect estimates numerically favored high doses of subcutaneous fremanezumab and intravenous eptinezumab as the effective therapy with acceptable safety and tolerability for short term prevention of chronic migraine., (Copyright © 2021 Elsevier B.V. All rights reserved.)