TY - JOUR

T1 - Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine

T2 - A pooled analysis of four placebo-controlled trials with long-term extensions

AU - Ashina, Messoud

AU - Kudrow, David

AU - Reuter, Uwe

AU - Dolezil, David

AU - Silberstein, Stephen

AU - Tepper, Stewart J.

AU - Xue, Fei

AU - Picard, Hernan

AU - Zhang, Feng

AU - Wang, Andrea

AU - Zhou, Yanchen

AU - Hong, Frank

AU - Klatt, Jan

AU - Mikol, Daniel D.

PY - 2019/12

Y1 - 2019/12

N2 - Background: Efficacy and safety of erenumab have been evaluated in a comprehensive clinical development program resulting in approval for migraine prevention in over 40 countries to date. Methods: This integrated safety analysis included four double-blind randomized trials and their extensions (up to three-plus years). Safety endpoints included exposure-adjusted patient incidences of adverse events, serious adverse events, and anti-erenumab antibodies. Results: In all, 2375 of the patients randomized across the four studies received at least one dose of erenumab (70 mg or 140 mg), with cumulative exposure of 2641.2 patient-years. Exposure-adjusted adverse event rates during the double-blind treatment phase were similar to placebo, with the exception of injection-site reactions (17.1 vs. 10.8 per 100 patient-years), constipation (7.0 vs. 3.8 per 100 patient-years), and muscle spasm (2.3 vs. 1.2 per 100 patient-years). During the long-term extensions, adverse events reported were similar to those observed during the double-blind treatment phase, and rates of injection site reactions, constipation, and muscle spasm were reported at lower rates than in the double-blind treatment phase. There were two deaths reported, both confounded by pre-existing conditions. Conclusions: This pooled safety analysis revealed a favorable and stable adverse event profile over time for erenumab with more than three years of exposure. Trial registration: ClinicalTrials.gov NCT01952574, NCT02483585, NCT02456740, NCT02066415, and NCT02174861.

AB - Background: Efficacy and safety of erenumab have been evaluated in a comprehensive clinical development program resulting in approval for migraine prevention in over 40 countries to date. Methods: This integrated safety analysis included four double-blind randomized trials and their extensions (up to three-plus years). Safety endpoints included exposure-adjusted patient incidences of adverse events, serious adverse events, and anti-erenumab antibodies. Results: In all, 2375 of the patients randomized across the four studies received at least one dose of erenumab (70 mg or 140 mg), with cumulative exposure of 2641.2 patient-years. Exposure-adjusted adverse event rates during the double-blind treatment phase were similar to placebo, with the exception of injection-site reactions (17.1 vs. 10.8 per 100 patient-years), constipation (7.0 vs. 3.8 per 100 patient-years), and muscle spasm (2.3 vs. 1.2 per 100 patient-years). During the long-term extensions, adverse events reported were similar to those observed during the double-blind treatment phase, and rates of injection site reactions, constipation, and muscle spasm were reported at lower rates than in the double-blind treatment phase. There were two deaths reported, both confounded by pre-existing conditions. Conclusions: This pooled safety analysis revealed a favorable and stable adverse event profile over time for erenumab with more than three years of exposure. Trial registration: ClinicalTrials.gov NCT01952574, NCT02483585, NCT02456740, NCT02066415, and NCT02174861.

KW - Erenumab

KW - migraine

KW - safety

U2 - 10.1177/0333102419888222

DO - 10.1177/0333102419888222

M3 - Journal article

C2 - 31707815

AN - SCOPUS:85075171377

VL - 39

SP - 1798

EP - 1808

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 14

ER -