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Randomized Controlled Trial
. 2023 Nov 20;24(1):155.
doi: 10.1186/s10194-023-01688-w.

Long-term effectiveness of eptinezumab in patients with migraine and prior preventive treatment failures: extension of a randomized controlled trial

Messoud Ashina  1   2 , Stewart J Tepper  3 , Astrid Gendolla  4 , Bjørn Sperling  5 , Anders Ettrup  5 , Mette Krog Josiassen  5 , Amaal J Starling  6
Affiliations
Randomized Controlled Trial

Long-term effectiveness of eptinezumab in patients with migraine and prior preventive treatment failures: extension of a randomized controlled trial

Messoud Ashina et al. J Headache Pain. .

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 ).

Keywords: Efficacy; Most bothersome symptom; Quality of life; Work productivity.

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Conflict of interest statement

Messoud Ashina reports receiving personal fees from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals during the conduct of the study. He reported serving as associate editor of Cephalalgia, associate editor of The Journal of Headache and Pain, and associate editor of Brain.

Stewart J. Tepper reports grants for research (no personal compensation): Allergan/AbbVie, Amgen, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, Zosano. Consultant and/or Advisory Boards (honoraria): Aeon, Allergan/AbbVie, Alphasights, Amgen, Aruene, Atheneum, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, ClickTherapeutics, CoolTech, CRG, Decision Resources, Defined Health, DRG, Eli Lilly, ExpertConnect, FCB Health, Fenix, GLG, Guidepoint Global, Health Advances, Health Science Communications, HMP Communications, Impel, Initiatior Pharma, InteractiveForums, Keyquest, Ki Health Partners, Krog and Partners, Lundbeck, M3 Global Research, Magnolia Innovation, MJH Holdings, Miravo Healthcare, Neurofront Therapeutics, Neurolief, Novartis, P Value Communications, Pain Insights, Inc., Palion Medical, Pfizer, Pulmatrix, Putnam Associates, Rehaler, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Strategy Inc., Synapse Medical Communication, System Analytic, Taylor and Francis, Tegus, Teva, Theranica, Tremeau, Trinity Partners, Unity HA, Vial, XOC, Zosano. Salary: Dartmouth-Hitchcock Medical Center and Thomas Jefferson University. CME honoraria: American Academy of Neurology, American Headache Society, Annenberg Center for Health Sciences, Catamount Medical Education, Diamond Headache Clinic, Forefront Collaborative, Haymarket Medical Education, HMP Global, Medical Education Speakers Network, Medical Learning Institute Peerview, Migraine Association of Ireland, Miller Medical Education, National Association for Continuing Education, North American Center for CME, The Ohio State University, Physicians’ Education Resource, PlatformQ Education, Primed, Vindico Medical Education, and WebMD/Medscape.

Astrid Gendolla has received honoraria for advisory boards and lectures from Novartis, Lilly, TEVA, Allergan/AbbVie, Mundipharma, Stada Arzneimittel, Grünenthal, Hormosan Pharma, Perfood, Lundbeck, and Pfizer within the past 3 years.

Bjørn Sperling, Anders Ettrup and Mette Krog Josiassen are current employees of H. Lundbeck A/S. Bjørn Sperling and Mette Krog Josiassen own stock in H. Lundbeck A/S.

Amaal J. Starling has received consulting fees from AbbVie, Allergan, Amgen, Axsome Therapeutics, eNeura, Everyday Health, Lundbeck, Med-IQ, Medscape, Miller Medical, Satsuma, and WebMD within the past 3 years.

Figures

Fig. 1
Fig. 1
CONSORT diagram of patient disposition.  Safety analyses were conducted in the all-patients-treated set, which included all randomized patients who received ≥ 1 infusion of double-blind study drug and had a visit in the extension period. Efficacy analyses were conducted in the full analysis set, which included all randomized patients who received ≥ 1 infusion of double-blind study drug, had a valid baseline assessment, and had ≥ 1 valid assessment of monthly migraine days in the extension period
Fig. 2
Fig. 2
Change from baseline in monthly migraine days (MMRM; efficacy analysis set).  BL, baseline; Epti, eptinezumab; LS, least squares; MMRM, mixed model for repeated measures
Fig. 3
Fig. 3
Patients achieving (A) ≥ 50% and (B) ≥ 75% reduction in monthly migraine days (efficacy analysis set). †n/N = 2/144; ‡n/N = 5/146. Epti, eptinezumab
Fig. 4
Fig. 4
Mean changes from baseline in HIT-6 total score (MMRM; efficacy analysis set). BL, baseline; Epti, eptinezumab; HIT-6, 6-item Headache Impact Test; LS, least squares; MMRM, mixed model for repeated measures
Fig. 5
Fig. 5
Mean changes from baseline in the percentage of migraine attacks that were severe (MMRM; efficacy analysis set). BL, baseline; Epti, eptinezumab; LS, least squares; MMRM, mixed model for repeated measures
Fig. 6
Fig. 6
Mean changes from baseline in acute migraine medication days/month (MMRM; efficacy analysis set). Acute migraine medication types included ergotamine, triptan, simple analgesic, combination analgesic, and opioid. BL, baseline; Epti, eptinezumab; LS, least squares; MMRM, mixed model for repeated measures
See this image and copyright information in PMC

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