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

To evaluate whether prior use of subcutaneous anti–calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) impacts the real-world effectiveness of eptinezumab in patients with chronic migraine (CM).

Longer periods between headache episodes (interictal periods) may provide greater time for the nervous system to reset from a previous episode, potentially improving disease status and health-related quality of life. This post hoc analysis evaluated this hypothesis by associating patients’ longest interictal periods with improvements in patient-reported outcomes. PROMISE-2 (NCT02974153) was a double-blind, placebo-controlled study evaluating eptinezumab for preventive treatment of chronic migraine (N = 1072). Daily electronic diary data from Weeks 1–12 and Weeks 1–24 were used to identify interictal periods, defined as days between headache episodes. For each patient, the longest interictal period within these intervals was identified and categorized (1–4, 5–9, 10–14, > 14, and > 21 days). For each category, the following patient-reported outcomes were assessed: 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and patient-identified most bothersome symptom (PI-MBS). Excluding interictal periods with > 10

To evaluate the real-world effectiveness of eptinezumab on "brain fog" and the number of "good" days/month in adults with chronic migraine (CM).

To evaluate whether the presence of psychiatric conditions impacts the real-world effectiveness of eptinezumab in patients with chronic migraine (CM).

Objective: To describe the patient response, including effects on disability and function, to eptinezumab in a real-world setting after 6 months of preventive migraine treatment. Background: The anti-calcitonin gene-related peptide monoclonal antibody eptinezumab is approved for the prevention of migraine in adults. Evidence from post-marketing studies is needed to better understand how eptinezumab prevents migraine in the real-world setting. Design/Methods: This retrospective chart review examined data from adults who initiated preventive treatment and received at least 2 infusions of eptinezumab (100mg or 300mg) at headache clinics between April and October 2020. Demographic information, treatment history, migraine and headache frequency, disease characteristics, and disability assessment scores (e.g., Migraine Disability Assessment [MIDAS], Headache Impact Test [HIT-6]) were collected using standardized case-report forms completed by physicians. These report forms measured patient and clinician perspectives on eptinezumab treatment response. Results: This analysis includes data from 31 patients with migraine (mean age, 50.7 years; 100% white [27/27]; 81.5% female [22/27]; 93.5% chronic migraine [29/31]) had been collected across 8 sites. Relative to baseline, 6 months of preventive treatment with eptinezumab reduced mean monthly headache days (23.5 at baseline, 16.3 at Month 6), mean monthly migraine days (17.9 at baseline, 9.1 at Month 6), and patient-reported disability (50.0% [11/22] severe at baseline per MIDAS and/or HIT-6, 36.8% [7/19] severe at Month 6). Eptinezumab treatment was also associated with reduced acute headache medication use (16.7 mean acute medication days per month in the last 3 months prior to treatment and 8.3 at Month 6). Clinicians reported that treatment was well-tolerated (96.8%) and improved disability/function (77.4%) after 6 months of use. Conclusions: Early clinical experience with eptinezumab and the magnitude of improvement is consistent with results reported in controlled clinical trials, with reductions in headache frequency and associated disability evident during the first 6 months of treatment. Disclosure: Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Seema Soni-Brahmbhatt has nothing to disclose. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck.

Treatment target goals for patients receiving preventive migraine treatment are complicated to assess and not achieved by most patients. A headache “number” could establish an understandable treatment target goal for patients with chronic migraine (CM). This study investigates the clinical impact of reduced headache frequency to ≤ 4 monthly headache days (MHDs) as a treatment-related migraine prevention target goal. All treatment arms were pooled for analysis from the PROMISE-2 trial evaluating eptinezumab for the preventive treatment of CM. Patients (N = 1072) received eptinezumab 100 mg, 300 mg, or placebo. Data for the 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), and acute medication use days were combined for all post-baseline assessments and analyzed by MHD frequency (≤ 4, 5–9, 10–15, > 15) in the 4 weeks preceding assessment. Based on pooled data, the percentage of patient-months with ≤ 4 MHDs associated with “very much improved” PGIC was 40.9 https://clinicaltrials.gov/ct2/show/NCT02974153 ).

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.

Objective: To demonstrate the lack of a "wearing off effect" with eptinezumab in preventive migraine treatment. Background: A "wearing off effect" is described as a positive response to treatment with a shorter duration of benefit than expected. Design/Methods: PROMISE-1 (NCT02559895) and PROMISE-2 (NCT02974153) were both phase 3, randomized, double-blind, placebo-controlled studies that evaluated the efficacy and safety of eptinezumab (administered every 12 weeks) for migraine prevention in adults with episodic or chronic migraine, respectively. PROMISE-1 and PROMISE-2 captured monthly migraine days (MMDs) for up to 48 weeks and 24 weeks of treatment, respectively. Using data on the change in MMDs, a post hoc closed testing analysis investigated the consistency of effect during the first dosing interval. The percentage of patients experiencing a migraine attack at intervals reduced by a single day was analyzed beginning with the primary endpoint interval (Weeks 1–12, or Days 1–84). Results: In both studies, eptinezumab 100mg and 300mg demonstrated greater reductions vs placebo in MMDs over 4-week intervals that were sustained across the respective treatment periods. The closed testing analysis showed that both doses achieved nominally significant differences (P<0.05) from Day 84 to Day 1 independently, indicating that eptinezumab was effective beginning Day 1 after dosing. Reductions from baseline were greater than the reduction for placebo across the entire curve. Similar magnitudes of effect over each 4-week interval at the population level suggests the onset of the migraine preventive effect of eptinezumab can be observed on Day 1 following initial dosing, with the effect sustained through the full 12 weeks. Conclusions: No statistically significant differences were found between the percentages of patients reporting migraine attack reduction on Day 1 and on any day through Day 84. In both pivotal trials for eptinezumab, there is no significant "wearing off" of eptinezumab's preventive benefit observed through Day 84. Disclosure: Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Seema Soni-Brahmbhatt has nothing to disclose. Dr. Dodick has received personal compensation for serving as an employee of Mayo Clinic. Dr. Dodick has received personal compensation for serving as an employee of Atria Health. Dr. Dodick has received personal compensation for serving as an employee of Thomas Jefferson University . Dr. Dodick has received personal compensation for serving as an employee of Norwegian University of Science and Technology. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Dodick has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Allergan. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biopharm Communications. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Inside Practice Australia. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Education Alliance. Dr. Dodick has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Headache Cooperative of the Pacific . Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medica Communications. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MJ Healthcare. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nocira. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Praxis. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance . Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Synapse Medical Communications. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vector Psychometrics. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as a Consultant for Ayya Biosciences. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as a Consultant for Theranica. Dr. Dodick has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Atria. Dr. Dodick has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for WebMD. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Thomas Jefferson University. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medforce. Dr. Dodick has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precision HEOR. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for KingDevick Technologies. Dr. Dodick has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Precon Health. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Ontologics. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Matterhorn. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Axon Therapeutics. Dr. Dodick has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Cephalgia Group. Dr. Dodick has stock in Healint. Dr. Dodick has stock in Theranica. Dr. Dodick has stock in Aural Analytics . Dr. Dodick has stock in Epien. Dr. Dodick has stock in Matterhorn. Dr. Dodick has stock in Ontologics. Dr. Dodick has stock in Precon Health. Dr. Dodick has stock in King Devick Technologies. Dr. Dodick has stock in Nocira. Dr. Dodick has stock in Exsano. Dr. Dodick has stock in Palion. Dr. Dodick has stock in AYYA Biosciences. Dr. Dodick has stock in Perfood. Dr. Dodick has stock in Cephalgia Group. Dr. Dodick has stock in Atria Health. Dr. Dodick has stock in Man and Science. The institution of Dr. Dodick has received research support from Department of Defense. The institution of Dr. Dodick has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Dodick has received research support from Henry Jackson Foundation. Dr. Dodick has received intellectual property interests from a discovery or technology relating to health care. Dr. Dodick has received intellectual property interests from a discovery or technology relating to health care. Dr. Dodick has received intellectual property interests from a discovery or technology relating to health care. Dr. Dodick has received publishing royalties from a publication relating to health care. Dr. Dodick has received publishing royalties from a publication relating to health care. Dr. Dodick has received publishing royalties from a publication relating to health care. Dr. Dodick has a non-compensated relationship as a Chair with American Brain Foundation that is relevant to AAN interests or activities. Dr. Dodick has a non-compensated relationship as a Committee member/Course Director with American Academy of Neurology that is relevant to AAN interests or activities. Dr. Dodick has a non-compensated relationship as a Chair/Immediate Past Chair with American Migraine Foundation that is relevant to AAN interests or activities. Dr. Dodick has a non-compensated relationship as a Chair Global Patient Advocacy Coalition with International Headache Society that is relevant to AAN interests or activities.

Objective: To assess the relative importance of 5 attributes in the choice of preventive migraine treatment from the patient perspective. Background: Anti-CGRP monoclonal antibodies and onabotulinumtoxinA have demonstrated efficacy and tolerability, the two most important migraine treatment attributes. Design/Methods: This non-interventional, cross-sectional study enrolled US adults with self-reported migraine diagnoses, who experienced ≥5 monthly migraine days, and had tried ≥2 prescription migraine treatments. A 25-minute discrete choice online survey was used to assess treatment preferences by having respondents select between two profiles that varied in attributes: speed of onset (24hr, 1wk, or 3mo), durability of prevention (wears off 1wk prior to next dose, 2wks prior to next dose, or does not wear off), mode of administration (IV, self-injection, or cranial injections), administration setting (at-home or in-office), and dosing frequency (1mo or 3mo). Hierarchical Bayes modeling estimated attribute-level preference weights. A latent class analysis identified subgroups that differed in their preferences. Results: 604 patients were analyzed. Mode of administration, durability of prevention, and speed of onset had the highest relative importance; administration setting and frequency of dosing had the lowest. Four groups with differing preferences were identified: those preferring auto-injection (n=128, 21%); those averse to cranial injections (n=189, 31%); those preferring faster speed of onset (n=158, 26%); and those preferring longer durability and clinicians to administer treatment (n=129, 21%). Except for those preferring auto-injection, all groups were willing to accept IV administration to achieve other treatment goals, indicating that three-fourths of participants were not averse to IV infusion as a route of administration. Conclusions: Among people living with migraine who have ≥5 monthly migraine days, important attributes of preventive migraine treatment were mode of administration, durability of effect, and speed of onset. Infusion as a route of administration was not considered a barrier for most patients. Disclosure: Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Schwedt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tonix Pharma. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biodelivery Science. Dr. Schwedt has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Linpharma. Dr. Schwedt has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Schwedt has stock in Aural Analytics. Dr. Schwedt has stock in Nocira. The institution of Dr. Schwedt has received research support from Amgen. The institution of Dr. Schwedt has received research support from National Institutes of Health. The institution of Dr. Schwedt has received research support from United States Department of Defense. The institution of Dr. Schwedt has received research support from Patient Centered Outcomes Research Institute. The institution of Dr. Schwedt has received research support from SPARK Neuro. The institution of Dr. Schwedt has received research support from Henry Jackson Foundation. Dr. Schwedt has received intellectual property interests from a discovery or technology relating to health care. Dr. Schwedt has received publishing royalties from a publication relating to health care. Dr. Martin has received personal compensation for serving as an employee of Cerner Enviza. The institution of Dr. Martin has received research support from Lundbeck LLC. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation. Dr. Talon has nothing to disclose. Ms. Lee has received personal compensation for serving as an employee of Lundbeck A/S. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Divya Asher has received personal compensation for serving as an employee of Lundbeck. Divya Asher has received personal compensation for serving as an employee of AbbVie. Meghana Karnik-Henry has received personal compensation for serving as an employee of Lundbeck. Ms. Mulvihill has received personal compensation for serving as an employee of Cerner Enviza, an Oracle Company. Ms. Bates has nothing to disclose. Ms. Beusterien has received personal compensation for serving as an employee of Cerner Enviza.

Background Eptinezumab 100 mg and 300 mg met the primary efficacy endpoint in both PROMISE clinical trials, significantly reducing frequency of monthly migraine days over Weeks 1‒12. The objective of this analysis was to assess the clinical response to eptinezumab 100 mg and 300 mg within the pivotal phase 3 PROMISE-1 and PROMISE-2 studies to potentially identify subsets of patients with meaningful differences between doses. Methods Patients from PROMISE-1 (NCT02559895) and PROMISE-2 (NCT02974153) trials were divided into subgroups based on demographic and migraine characteristics, and baseline questionnaire responses. For each subgroup, the overall likelihood of achieving ≥ 50% migraine responder rate (MRR) over Weeks 1–12 and Weeks 13–24 with either eptinezumab 100 mg or 300 mg was calculated using odds ratios (with associated confidence intervals) and compared. Results In PROMISE-1 (episodic migraine) and PROMISE-2 (chronic migraine), the likelihood of achieving ≥ 50% MRR over Weeks 1–12 and Weeks 13–24 was roughly equivalent for patients receiving either dose level of eptinezumab. Given the number of comparisons performed, sporadic apparent differences were seen but no replicated patterns between studies emerged. In PROMISE-1, no differences were observed in any subgroup over Weeks 1–12. In PROMISE-2, patients reporting < 15 monthly migraine days at baseline, any problems with mobility per the EQ-5D-5L, or a social functioning score > 45.0 per the 36-item Short-Form Health Survey (SF-36), appeared more likely to achieve ≥ 50% MRR with 300 mg over Weeks 1–12, with none of these being apparent in PROMISE-1. Conclusions Overall, these data suggest that across PROMISE-1 and PROMISE-2, there were no meaningful differences in the likelihood of achieving ≥ 50% MRR between the eptinezumab dose levels in the majority of patient subgroups. In the few subgroups that displayed small, but potentially meaningful differences, patients were more likely to achieve ≥ 50% MRR with eptinezumab 300 mg; however, minimal consistency across both studies and time periods was noted. Trial Registration ClinicalTrials.gov. PROMISE-1: NCT02559895 . PROMISE-2: NCT02974153 .

Objective: To assess preferences among adults with migraine for differentiating attributes of injected or infused preventive treatment options and evaluate their importance in determining a treatment choice.Background: Adults with migraine and health-care providers consider many factors when making treatment decisions. Injected or infused preventive migraine treatment options differ in several attributes, including mode of administration and dosing frequency, which may be preferentially selected or avoided by patients. Understanding a patient's preference is important for clinicians as they advise on various treatment options.Methods: A total of 604 US adults diagnosed with migraine participated in an online survey that captured information on demographics, migraine history, and treatment preferences. A discrete choice experiment (DCE) was used to evaluate participants' preferences for specific attributes of injected/infused preventive migraine therapies. The DCE data were utilized to estimate attribute importance (expressed as a percentage) and identify subgroups that had different distributions of preferences.Results: In the overall migraine population, mode of administration (28.8%), durability of effectiveness (27.0%), and speed of onset (25.5%) had the highest relative importance, whereas administration setting (9.9%) and dosing frequency (8.8%) had the lowest. Four distinct subgroups were identified: Group 1 (n = 128) preferred self-injection administration and durability of effectiveness; Group 2 (n = 189) expressed aversion to cranial injections; Group 3 (n = 158) prioritized rapid speed of onset; and Group 4 (n = 129) favored health-care provider administration and durability of effectiveness.Conclusions: Speed of onset, durability of effectiveness, and mode of administration are key moderators of treatment preference among US adults with migraine. Certain segments of the migraine population prioritize specific treatment attributes over others, with intravenous infusion not considered a barrier in three of four identified segments. Clinicians can best help their patients find the right medication if they understand which medication attributes are most and least important to them.