Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial

Abstract

Background: Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine.

Methods: PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase. Adults with chronic migraine received eptinezumab 300 mg by 30-min intravenous administration every 12 weeks for up to 8 doses. Patients were followed for 20 weeks after the final infusion (end-of-study visit at week 104).

Results: Overall, 128 adults (mean age, 41.5 years) with chronic migraine were included. During the 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). The rate of study-drug discontinuation due to adverse events was 6.3%, which included 3 patients with infusion-related hypersensitivity. The incidence of anti-eptinezumab antibodies peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Improvements in patient-reported outcomes were observed at first assessment (week 4) and generally sustained through week 104.

Conclusion: In adults with chronic migraine, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years.

Trial registration: ClinicalTrials.gov (Identifier: NCT02985398 ).

Keywords: Chronic migraine; Effectiveness; Eptinezumab; Immunogenicity; Safety.

Conflict of interest statement

● D. Kudrow: Advisory board and/or speaker: Amgen, Biohaven, Eli Lilly, Lundbeck Seattle BioPharmaceuticals, Novartis, Promius Pharma; Research support: Allergan, Amgen, Biohaven, Eli Lilly, Genentech, Lundbeck Seattle BioPharmaceuticals, Novartis, Roche Pharma, Teva, UCB, ViroMed; Speaker’s Bureau: Amgen/Novartis, Eli Lilly.

● R. Cady, S. Pederson, L. Mehta: Full-time employee: Lundbeck Seattle BioPharmaceuticals.

● B. Allan: Full-time employee at the time of study: Alder Biopharmaceuticals (CKA Lundbeck Seattle Biopharmaceuticals).

● J. Hirman: Contracted service provider of biostatistical resources: Lundbeck Seattle BioPharmaceuticals.

● B. Schaeffler: Full-time employee at the time of the study and during manuscript development: Lundbeck Seattle BioPharmaceuticals.

Figures

Fig. 1

Patient disposition

Fig. 2

Migraine Disability Assessment total score, by visit: (a) mean changes from baseline and (b) level of disability. Mean Migraine Disability Assessment total score at baseline: 56.8. The level of disability in daily functioning was graded using the Migraine Disability Assessment total score: 0–5 days, grade I (little or no disability); 6–10 days, grade II (mild disability); 11–20 days, grade III (moderate disability); 21+ days, grade IV (severe disability) [15]

Fig. 3

Patient-identified most bothersome symptom: change from baseline at weeks 4 and 48. *Worse includes minimally worse, much worse, and very much worse. Not collected beyond week 48

Fig. 4

Patient Global Impression of Change: percentage of patients “much improved” or “very much improved” at each assessment

Fig. 5

Headache Impact Test: mean total score at each assessment. Baseline: n = 128; mean = 65.2