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

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 Abstrac

Correction: Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-022-02714-1

sj-jpg-3-cep-10.1177_03331024231170807 - Supplemental material for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study

Supplemental material, sj-jpg-3-cep-10.1177_03331024231170807 for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study by Messoud Ashina, Michel Lanteri-Minet, Anders Ettrup, Cecilie Laurberg Christoffersen, Mette Krog Josiassen, Ravinder Phul, Bjørn Sperling and Patricia Pozo-Rosich in Cephalalgia</p

sj-jpg-4-cep-10.1177_03331024231170807 - Supplemental material for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study

Supplemental material, sj-jpg-4-cep-10.1177_03331024231170807 for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study by Messoud Ashina, Michel Lanteri-Minet, Anders Ettrup, Cecilie Laurberg Christoffersen, Mette Krog Josiassen, Ravinder Phul, Bjørn Sperling and Patricia Pozo-Rosich in Cephalalgia</p

sj-jpg-5-cep-10.1177_03331024231170807 - Supplemental material for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study

Supplemental material, sj-jpg-5-cep-10.1177_03331024231170807 for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study by Messoud Ashina, Michel Lanteri-Minet, Anders Ettrup, Cecilie Laurberg Christoffersen, Mette Krog Josiassen, Ravinder Phul, Bjørn Sperling and Patricia Pozo-Rosich in Cephalalgia</p

sj-jpg-2-cep-10.1177_03331024231170807 - Supplemental material for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study

Supplemental material, sj-jpg-2-cep-10.1177_03331024231170807 for Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study by Messoud Ashina, Michel Lanteri-Minet, Anders Ettrup, Cecilie Laurberg Christoffersen, Mette Krog Josiassen, Ravinder Phul, Bjørn Sperling and Patricia Pozo-Rosich in Cephalalgia</p