BACKGROUND:This post hoc analysis examined the reduction in monthly headache days (MHDs) by frequency category shifts and associated improvements following eptinezumab treatment. METHODS:The DELIVER trial evaluated eptinezumab in adults with migraine for whom 2-4 previous preventive treatments failed. During a 24-week, double-blind, placebo-controlled period followed by a 48-week extension period, participants received IV eptinezumab 100 mg, 300 mg, or placebo every 12 weeks, with all receiving eptinezumab beginning Week 25 (dose-blinded). Participants were categorized by MHD frequency: > 14, 8-14, 4 to < 8, 1 to < 4, 0. MHD category shifts were evaluated in the total population and several subgroups (including participants with > 14 baseline MHDs and early ≥ 50% responders). In participants reporting < 8 MHDs after all doses, the associated changes in headache intensity and disease status were evaluated. RESULTS:Of randomized participants, 88% (782/890) completed the trial. The percentage of participants randomized initially to eptinezumab who reported < 4 MHDs was 23% (138/592) over Weeks 1-12 and 47% (236/498) over Weeks 61-72; 9% reported 0 MHDs after the final dose. Of participants randomized initially to eptinezumab who shifted from ≥ 8 MHDs at baseline to < 8 over Weeks 1-12, 71% (170/241) reported < 8 MHDs for the rest of the trial; of those who shifted from > 14 to < 8 MHDs, 66% (49/74) reported < 8 MHDs for the rest of the trial. Reduction to < 8 MHDs was associated with robust improvements in headache intensity and disease burden. CONCLUSIONS:Eptinezumab was associated with sustained reduction in MHD category, with some achieving headache/migraine freedom in patients with a history of preventive treatments that failed. TRIAL REGISTRATION:ClinicalTrials.gov (identifier: NCT04418765; https://www. CLINICALTRIALS:gov/ct2/show/NCT04418765) and EudraCT (identifier: 2019-004497-25; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25).

To determine the shift in headache frequency categories among eptinezumab-treated patients within the DELIVER clinical trial.

In the DELIVER study, eptinezumab reduced monthly migraine days (MMDs) more than placebo in patients with 2–4 prior preventive migraine treatment failures. This post hoc analysis evaluated the efficacy of eptinezumab across the 24-week placebo-controlled period of the DELIVER study in subgroups defined by prior treatment failure type. DELIVER (NCT04418765) randomized adults with migraine to eptinezumab 100 mg, 300 mg, or placebo, administered intravenously every 12 weeks. Changes from baseline in MMDs and percentages of patients with ≥ 50

Introduction Dans DELIVER, eptinezumab a entrainé une réduction plus importante du nombre de jours mensuels de migraine (JMM) par rapport au placebo, chez des patients en échec à 2–4 traitements préventifs. Objectifs Évaluer la persistance de la réponse à eptinezumab sur une période de 24 semaines et évaluer la probabilité d’une réponse à la 2de administration chez les patients initialement non répondeurs. Méthodes DELIVER a évalué eptinezumab 100mg et 300mg toutes les 12 semaines vs placebo chez des patients migraineux en échec. L’évaluation comprenait : les taux de répondeurs (TR)≥30 %, ≥50 %, et≥75 % (proportion de patients présentant une réduction des JMM depuis l’inclusion) sur les semaines 1–12 (Sem 1–12) et 13–24 (Sem 13–24), les TR par intervalles de 4 semaines et la proportion de patients initialement non répondeurs (réponse<30 %) qui atteignent une réponse après la 2e administration. Résultats L’étude a inclus 890 patients. Entre Sem 1–12 et Sem 13–24, le TR≥30 % a augmenté de 65,9 % à 70,4 % (100mg), 71,0 % à 74,5 % (300mg), versus 36,9 % à 43,1 % (placebo ; p<0,0001). Les TR≥30 %, ≥50 %, et≥75 % par intervalles de 4 semaines étaient généralement maintenus, avec une augmentation notable après la 2de administration d’eptinezumab. Parmi les patients non-répondeurs sur Sem 1–12, 34,7 % (100mg), 30,4 % (300mg) et 21,1 % (placebo) présentaient une réponse≥30 % sur Sem 13–24 (Fig. 1). Discussion N/A. Conclusion La majorité des patients qui présentait une réponse à eptinezumab sur Sem 1–12, maintenait la réponse sur Sem 13–24. Environ 1/3 des patients initialement non-répondeurs, devenaient répondeurs après la 2de administration.

To evaluate the 18-month maintenance of ≥50% migraine response in patients who experienced ≥50% migraine response with early doses of eptinezumab.

Introduction L’étude DELIVER a évalué l’efficacité et la sécurité d’eptinezumab dans le traitement préventif de la migraine chez des patients en échec aux traitements préventifs antérieurs. Objectifs Évaluer l’efficacité et la sécurité à long terme d’eptinezumab au cours de la phase d’extension de 48 semaines, conduite en aveugle de dose, de l’étude DELIVER. Méthodes DELIVER a évalué eptinezumab 100mg et 300mg (toutes les 12 semaines) vs placebo. Les patients randomisés sous placebo, durant la phase initiale, ont été randomisés pour recevoir eptinezumab 100mg ou 300mg dans la phase d’extension ; les patients initialement randomisés sous eptinezumab poursuivaient le même dosage. L’évaluation comprenait : le nombre de Jours mensuel de migraine (JMM), les taux de répondeurs, le score HIT-6, l’intensité de la migraine et l’utilisation des traitements de la crise. Résultats Au total, 782/865 patients (90,4 %) ont complété la phase d’extension de 48 semaines. Chez les patients initialement traités par placebo, la 1re injection d’eptinezumab a entraîné une réduction des JMM, de l’intensité de la migraine, de l’utilisation des traitements de la crise et du score HIT-6, similaire aux résultats observés sur les semaines 1 à 12. La réduction des JMM s’est maintenue dans l’ensemble des bras de traitement. Aucun nouveau signal de sécurité n’a été identifié (Fig. 1). Discussion N/A. Conclusion La réduction prolongée des JMM et de l’impact lié à la migraine, observée lors de la phase d’extension de DELIVER, confirme l’efficacité à long terme (18 mois) d’eptinezumab.

Abstract Background Eptinezumab demonstrated efficacy in adults with migraine and prior preventive treatment failures in the placebo-controlled phase of the DELIVER clinical trial; its long-term effectiveness in this population has not yet been reported. The objective of this study was to evaluate the long-term effectiveness of eptinezumab in a migraine patient population during the 48-week extension phase of DELIVER. Methods DELIVER was conducted June 1, 2020 to September 15, 2022. 865 adults with migraine, with documented evidence of 2–4 prior preventive migraine treatment failures and with completion of the 24-week placebo-controlled period of DELIVER received eptinezumab (100 or 300 mg) during the dose-blinded extension, either continuing their randomized dose or, if originally receiving placebo, were randomized 1:1 to an eptinezumab dose (100 or 300 mg). A mixed model for repeated measures was used to evaluate changes from baseline in the number of monthly migraine days (MMDs). Results Of 865 patients entering the extension (eptinezumab 100 mg, n = 433; 300 mg, n = 432), 782 (90.4%) completed and 11 (1.3%) discontinued due to an adverse event. Eptinezumab was associated with early and sustained reductions in migraine frequency. Mean MMDs at baseline were approximately 14 days across groups. Mean (standard error) change from baseline in MMDs over the final dosing interval (weeks 61–72) was −6.4 (0.50) with placebo/eptinezumab 100 mg, –7.3 (0.49) with placebo/eptinezumab 300 mg, –7.1 (0.39) with eptinezumab 100 mg, and −7.0 (0.39) with eptinezumab 300 mg. During weeks 61–72, 63–70% of patients demonstrated ≥ 50% reduction in MMDs, and 36–45% demonstrated ≥ 75% reduction. Headache severity and acute medication use reductions, and patient-reported improvements in most bothersome symptom, disease status, quality of life, and work productivity, were observed. Adverse events were generally mild, transient, and similar in frequency/type to previous eptinezumab trials. Conclusions The long-term effectiveness and safety/tolerability of eptinezumab in patients with migraine and 2–4 prior preventive treatment failures was demonstrated by high completion rates and migraine-preventive benefits sustained for up to 18 months, implying that eptinezumab is a viable long-term treatment option for patients still seeking successful migraine treatments. Trial registration ClinicalTrials.gov (Identifier: NCT04418765; URL: https://www.clinicaltrials.gov/ct2/show/NCT04418765 ); EudraCT (Identifier: 2019-004497-25; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25 ). Graphical Abstract

BackgroundMigraine 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. MethodsMigraine 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. ResultsEptinezumab 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. ConclusionEptinezumab 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.

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.

Dans l'étude DELIVER, eptinezumab a entraîné une réduction statistiquement significative du nombre de jours mensuels de migraine (JMM) par rapport au placebo, chez des patients migraineux en échec aux traitements préventifs antérieurs. Cette analyse exploratoire a évalué l'efficacité préventive de eptinezumab dans différents sous-groupes de patients inclus dans l'étude DELIVER (NCT04418765). DELIVER est une étude multicentrique, en double aveugle dans laquelle les patients ont été randomisés pour recevoir eptinezumab 100 mg, 300 mg, ou un placebo (IV toutes les 12 semaines). Les patients présentaient une migraine épisodique (ME) ou chronique (MC) et un échec de 2–4 traitements. Le critère principal d'évaluation (variation du nombre de JMM entre l'inclusion et les semaines 1 à 12) a été analysé dans différents sous-groupes (sexe, type de migraine, diagnostic de céphalée par abus médicamenteux (CAM), nombre d'échec antérieurs). Dans l'ensemble des sous-groupes, les patients traités par eptinezumab ont présenté une réduction du nombre de JMM entre l'inclusion et les semaines 1 à 12. La différence par rapport au placebo était numériquement plus importante chez les patients CAM vs population totale, chez les patients MC versus ME, chez les patients ME haute fréquence versus ME basse fréquence, chez les patients avec > 2 échecs versus 2 échecs. N/A. Parmi les sous-groupes explorés, une réduction plus importante du nombre de JMM sur les semaines 1 à 12 a été observée avec eptinezumab versus placebo chez les patients CAM, MC et avec > 2 échecs.

Objective: To report the consistency of response to eptinezumab and potential for response in initial non-responders in patients with prior preventive treatment failures. Background: Eptinezumab is an intravenous anti-calcitonin gene-related peptide monoclonal antibody approved for preventive treatment of migraine. In the DELIVER study, eptinezumab treatment resulted in greater reductions than placebo in monthly migraine days (MMDs). Design/Methods: DELIVER (NCT04418765) randomized adults with episodic or chronic migraine and 2–4 prior preventive treatment failures to infusion with eptinezumab 100mg, 300mg, or placebo every 12 weeks. Migraine responder rates (MRRs) of ≥30%, ≥50%, and ≥75% over Weeks 1–12 and 13–24, MRRs over 4-week intervals, and the percentage of initial non-responders (Weeks 1–12) achieving response to their second infusion (Weeks 13–24) were calculated. MRRs are calculated as an average percentage change from baseline in MMDs over the specified interval. Results: The full analysis set included 890 patients (100mg, n=299; 300mg, n=293; placebo, n=298). Between Weeks 1–12 and 13–24, respectively, ≥30% MRRs increased from 65.9% to 70.4% (100mg), from 71.0% to 74.5% (300mg), versus 36.9% to 43.1% (placebo; P<0. 0001 for both doses/timepoints vs placebo). The ≥30%, ≥50%, and ≥75% MRRs were generally maintained or further increased over the 24-week period, with further numerical increases in responder rates observed after the second eptinezumab infusion. Across treatment groups, response over Weeks 1–12 was generally maintained over Weeks 13–24; however, of patients with <30% response over Weeks 1–12, 34.7% (100mg), 30.4% (300mg), vs 21.1% (placebo) achieved ≥30% response over Weeks 13–24, and 16.8% (100mg), 15.2% (300mg), vs 6.5% (placebo) achieved ≥50% response. Conclusions: Across MRR thresholds, most patients who responded to eptinezumab during Weeks 1–12 maintained response during Weeks 13–24, with responder rates further increasing from the first to the second infusion. Approximately one-third of initial non-responders became responders after their second infusion. Disclosure: Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Ashina has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck/Alder. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nesos. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GlaxoSmithKline. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BiodeliveryScienceIndustry. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miravo. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Impel. Dr. Ailani has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Ailani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome. Dr. Ailani has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lindpharma. Dr. Ailani has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Report. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Live. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medscape. Dr. Ailani has stock in Ctrl M. The institution of Dr. Ailani has received research support from Allergan/Abbvie. The institution of Dr. Ailani has received research support from Eli Lilly. The institution of Dr. Ailani has received research support from Zosano. Dr. Ailani has received research support from Satsuma. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Advisory Panel with Medscape. Dr. Ailani has received personal compensation in the range of $500-$4,999 for serving as a Medical Advisor with SELF. Jan Versijpt has nothing to disclose. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Sacco has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lilly. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Prof. Sacco has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Lundbeck. Prof. Sacco has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Allergan. Prof. Sacco has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. The institution of Prof. Sacco has received research support from Novartis. Prof. Sacco has a non-compensated relationship as a President elect with European Stroke Organisation that is relevant to AAN interests or activities. Prof. Sacco has a non-compensated relationship as a Second vice President with European Headache Federation that is relevant to AAN interests or activities. The institution of Dr. Mitsikostas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. The institution of Dr. Mitsikostas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. Mitsikostas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for TEVA. The institution of Dr. Mitsikostas has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Leli Lilly. The institution of Dr. Mitsikostas has received research support from Eli Lilly. Dr. Mitsikostas has a non-compensated relationship as a Co-Chair of Headache Panel with EAN that is relevant to AAN interests or activities. Dr. Mitsikostas has a non-compensated relationship as a President with Hellenic Headache Society that is relevant to AAN interests or activities. Dr. Mitsikostas has a non-compensated relationship as a Associate Editor with J Headache Pain that is relevant to AAN interests or activities. Dr. Mitsikostas has a non-compensated relationship as a Associate Editor with Frontier Neurology that is relevant to AAN interests or activities. Mrs. Christoffersen has received personal compensation for serving as an employee of H. Lundbeck A/S. An immediate family member of Mrs. Christoffersen has received personal compensation for serving as an employee of Cytovac A/S. Bjoern Sperling has received personal compensation for serving as an employee of Lundbeck . Bjoern Sperling has stock in Lundbeck . Anders Ettrup has received personal compensation for serving as an employee of H. Lundbeck A/S.

Dans l'étude DELIVER, eptinezumab, un anticorps monoclonal anti-calcitonin gene-related peptide (CGRP), a réduit la fréquence des migraines et était bien toléré chez les patients souffrant de migraine en échec aux traitements préventifs antérieurs. Cette analyse a évalué les changements dans les patient reported outcomes (PRO – résultats rapportés par le patient) au cours de la période en double aveugle de 24 semaines. Dans l'étude DELIVER (NCT04418765), les patients migraineux en échec à 2–4 traitements préventifs antérieurs ont été randomisés pour recevoir eptinezumab 100 mg, 300 mg ou un placebo toutes les 12 semaines en intraveineuse. Les PROs évalués incluaient l'échelle visuelle analogique EuroQol (EQ-5D-5L EVA), les questionnaires HIT-6 (questionnaire d'impact des céphalées), PGIC (impression globale de changement par le patient), MBS (symptôme le plus incommodant) et MSQ (questionnaire de qualité de vie spécifique de la migraine). La variation moyenne à la semaine 12 (S12) du score EQ-5D-5L EVA était de 2,0 (100 mg, p = 0,0007) et 4,4 (300 mg, p < 0,0001) versus −3,1 (placebo), et était maintenue à S24. Le score HIT-6 moyen à l'inclusion était de ∼66,4 ; la variation moyenne était de −6,9 (100 mg, p < 0,0001) et −8,5 (300 mg, p < 0,0001) versus −3,1 (placebo) à S12 et augmentait à S24 (−8,9, −9,9 vs −3,9). Une variation plus importante des scores MSQ était observée avec eptinezumab versus placebo. N/A. Chez les patients en échec aux traitements préventifs de la migraine, eptinezumab a entraîné une amélioration de la qualité de vie et du fardeau lié à la migraine sur 24 semaines, par rapport au placebo.

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.

Abstract Background Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom (MBS; including nausea, photophobia, or phonophobia) compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (P < .05) on headache- and migraine-associated symptoms when administered during a migraine attack. Methods RELIEF, a multicenter, parallel-group, double-blind trial, occurred from November 7, 2019, through July 8, 2020. Adults considered candidates for preventive treatment were randomized to eptinezumab 100 mg (N = 238) or placebo (N = 242) administered intravenously over 30 min within 1–6 h of migraine onset. Outcome measures included headache pain freedom/relief and absence of MBS, patient’s choice of photophobia, phonophobia, or nausea, at regular intervals from 0.5 to 48 h after infusion start. Censoring was applied at time of acute rescue medication use. Results At hour 1, more eptinezumab-treated patients achieved headache pain freedom (9.7%), headache pain relief (38.7%), and absence of MBS (33.2%) versus placebo (4.1%, 26.9%, and 22.1%, respectively; P < .05 all), with separation from placebo (P < .05) through hour 48. Eptinezumab separated from placebo (P < .05) at hour 1 in absence-of-photophobia (29.4% vs 17.0%) and absence-of-phonophobia (41.2% vs 27.2%) and through hour 48. Initial separation from placebo (P < .05) in absence-of-nausea occurred at end-of-infusion (0.5 h; 36.7% vs 25.4%, respectively). Conclusion Preventive treatment with eptinezumab initiated during a migraine attack resulted in more patients achieving headache pain freedom/relief and absence of MBS, with separation from placebo (P < .05) as early as 0.5–1 h following the start of infusion. Rapid resolution of headache- and migraine-associated symptoms by a peripherally acting, intravenously administered antibody suggest a peripheral site of pharmacological action for CGRP blockade. Trial registration ClinicalTrials.gov Identifier: NCT04152083 .

Abstract Background The multinational phase 3b DELIVER trial was designed to evaluate the efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures across 17 countries. In the placebo-controlled portion, eptinezumab relative to placebo demonstrated greater reductions in migraine and headache frequency, migraine and headache severity, and acute medication use. The objective of this report is to describe the effects of eptinezumab on self-reported work productivity in the placebo-controlled portion of DELIVER. Methods Adults 18–75 years of age with migraine and documented evidence of 2 to 4 prior preventive treatment failures in the past 10 years were randomized to receive eptinezumab 100 mg, 300 mg, or placebo intravenously (IV) every 12 weeks. The Work Productivity and Activity Impairment questionnaire specific to migraine (WPAI:M), which comprises 6 items (4 of which are completed by currently employed patients only), was administered every 4 weeks. Changes from baseline in subscores (absenteeism, presenteeism, work productivity loss, and activity impairment) were calculated based on item responses. A mixed model for repeated measures was used to analyze changes from baseline in WPAI:M subscores. Results A total of 890 adults (mean age, 43.8 years) were included in the full analysis set (eptinezumab 100 mg, n = 299; eptinezumab 300 mg, n = 293; placebo, n = 298). Mean WPAI:M subscores at baseline indicated a negative impact of migraine attacks on work productivity and ability to complete normal daily activities. Eptinezumab improved WPAI:M subscores more than placebo at all assessment points throughout the study. Mean changes from baseline in self-reported work productivity loss were −19.5, −24.0, and −9.7 at Week 12; and −22.6, −20.2, and −7.2 at Week 24 (all P < 0.001 vs placebo) for eptinezumab 100 mg, eptinezumab 300 mg, and placebo, respectively. Mean changes from baseline in activity impairment were −21.3, −23.8, and −11.2 at Week 12; and −24.7, −22.6, and −10.1 at Week 24 (all P < 0.0001 vs placebo). Similarly, mean improvements in absenteeism and presenteeism were greater in the eptinezumab groups than in the groups receiving placebo at all timepoints (P < 0.05). Conclusion In adults with migraine and prior preventive treatment failure, eptinezumab 100 mg and 300 mg IV every 12 weeks improved absenteeism, presenteeism, work productivity loss, and activity impairment more than placebo. Trial registration ClinicalTrials.gov (Identifier: NCT04418765 ); EudraCT (Identifier: 2019–004497-25) ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004497-25/PL ). Graphical Abstract Eptinezumab improves self-reported work productivity in patients with migraine and prior preventive treatment failures.

Background The monoclonal antibody eptinezumab, which targets calcitonin gene-related peptide, has shown migraine preventive effects starting the day following infusion and acceptable safety and tolerability in phase 3 trials, but benefits in the subpopulations of patients with previous preventive treatment failures were not examined. We aimed to investigate the safety and efficacy of eptinezumab for migraine prevention in adults with migraine and two-to-four previous preventive treatment failures. Methods DELIVER was a multicentre, multi-arm, phase 3b trial comprising a 24-week double-blind, placebo-controlled period and a 48-week dose-blinded extension. We recruited adults with episodic or chronic migraine with at least 4 monthly migraine days (as per International Headache Society guidelines) and documented evidence of two-to-four previous preventive treatment failures within the past 10 years, from 96 study locations across Europe (n=93) and the USA (n=3). Patients were randomly assigned (1:1:1) via a centralised randomisation system, stratified by baseline monthly headache days and country, to eptinezumab 100 mg, eptinezumab 300 mg, or placebo. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (captured using a daily electronic diary) in weeks 1-12, assessed in the full analysis set. All participants and study personnel were masked to study drug assignments. The dose-blinded extension period is ongoing. Findings Between June 1, 2020, and Oct 7, 2021, 891 individuals were randomly assigned and received at least one dose of study drug (safety population; eptinezumab 100 mg n=299 [34%], eptinezumab 300 mg n=294 [33%], placebo n=298 [33%]). 865 patients completed the placebo-controlled period. The change from baseline to weeks 1-12 in mean monthly migraine days was -4.8 (SE 0.37) with eptinezumab 100 mg, -5.3 (0.37) with eptinezumab 300 mg, and -2.1 (0.38) with placebo. The difference from placebo in change in mean monthly migraine days from baseline was significant with eptinezumab 100 mg (-2.7 [95% CI -3.4 to -2.0]; p<0.0001) and eptinezumab 300 mg (-3.2 [-3.9 to -2.5]; p<0.0001). Treatment-emergent adverse events occurred in 127 (42%) of 299 patients in the eptinezumab 100 mg group, in 120 (41%) of 294 in the eptinezumab 300 mg group, and in 119 (40%) of 298 in the placebo group. The most common treatment-emergent adverse event was COVID-19 (20 [7%] of 299 patients in the eptinezumab 100 mg group, 17 [6%] of 294 in the eptinezumab 300 mg group, and 16 [5%] of 298 in the placebo group). Serious adverse events were uncommon (five [2%] of 299 in the eptinezumab 100 mg group, seven [2%] of 294 in the eptinezumab 300 mg group, four [1%] of 298 in the placebo group) and included anaphylactic reaction (eptinezumab 300 mg n=2) and COVID-19 (eptinezumab 100 mg n=1 and eptinezumab 300 mg n=1). Interpretation In adults with migraine and two-to-four previous preventive treatment failures, eptinezumab provided significant migraine preventive effects compared with placebo, with acceptable safety and tolerability, indicating that eptinezumab might be an effective treatment option for this patient population. The dose-blinded extension period will provide additional long-term safety data in patients with migraine and previous preventive treatment failures. Copyright (C) 2022. Published by Elsevier Ltd. All rights reserved.

To comprehensively evaluate the safety and tolerability of eptinezumab in patients with migraine.

Background The humanized anti-CGRP monoclonal antibody eptinezumab has been evaluated in five large-scale clinical trials conducted in patients with migraine. This integrated analysis was conducted to evaluate the comprehensive safety and tolerability of eptinezumab in patients with migraine across these studies. Methods Data were pooled from four randomized, double-blind, placebo-controlled studies and the first year of one open-label study. Results The pooled population comprised 2867 adults with migraine: eptinezumab, n = 2076 (4797 infusions); placebo, n = 791 (1675 infusions). A total of 1137/2076 (54.8%) patients who received eptinezumab and 414/791 (52.3%) patients who received placebo experienced ≥1 treatment-emergent adverse event (TEAE); rates were similar across eptinezumab dose groups (10–1000 mg). For most patients with TEAEs, the events were mild or moderate in severity and considered unrelated to study drug by the investigators. Thirty infusion-site AEs occurred in 27/2076 (1.3%) patients who received eptinezumab and 7 in 7/791 (0.9%) patients who received placebo. Infusion-site AEs led to infusion interruption in 19/2076 (0.9%) and 5/791 (0.6%) patients in the eptinezumab and placebo groups, respectively. Nasopharyngitis occurred in ≥2% of patients in the eptinezumab 300-mg group and with an incidence of at least 2 percentage points greater than in the placebo group; however, in most patients (eptinezumab, 139/140; placebo 40/41), its occurrence was considered not related to study treatment. Adverse events coded to hypersensitivity occurred for 23/2076 (1.1%) patients treated with eptinezumab and no patients in the placebo group. If additional TEAE terms that could indicate hypersensitivity are considered (e.g., urticaria, flushing/hot flush, rash, and pruritus), hypersensitivity reactions in the two pivotal placebo-controlled phase 3 studies occurred in ≥2% of patients in the eptinezumab 100-mg and 300-mg groups, and the incidence was at least 2 percentage points greater in either of these groups than in the placebo group. Most hypersensitivity reactions were not serious and resolved with standard medical treatment or observation without treatment, usually within 1 day. Conclusions In adults with migraine, the intravenous administration of eptinezumab every 12 weeks demonstrated a favorable safety and tolerability profile. Trial registration ClinicalTrials.gov (Identifiers: NCT01772524 , NCT02275117 , NCT02559895 , NCT02974153 , NCT02985398 ).