Long-Term Safety and Efficacy of Erenumab for Episodic Migraines

April 2022

Patients with migraines often need to take medication for years; therefore, it is important to understand the long-term safety and tolerability of migraine therapies. One approved therapy for migraines is monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor.

Erenumab is a CGRP antagonist that has been shown in multiple double-blind randomized clinical trials to improve migraine frequency. To gain insight into long-term safety and efficacy, investigators conducted an open-label study following up on an earlier phase 2 trial that examined the use of erenumab versus placebo for 12 weeks to treat episodic migraines. The team previously published a 1-year interim safety and efficacy study as well as a 3-year safety study with the same participants who completed the phase 2 trial. This new report is the final safety and efficacy analysis after 5 years of treatment.

Participants in the phase 2, double-blind randomized trial had 4 to 14 migraine days and fewer than 15 total headache days per month for ≥1 years. In the open-label follow-up, all participants were given the highest dose of erenumab used in the double-blind trial (70 mg). A protocol amendment later allowed that dose to be doubled during the open-label follow-up to 140 mg. A total of 383 patients were enrolled in the double-blind trial, 215 of whom completed the follow-up study.

The main outcomes of the follow-up study were safety, tolerability, and efficacy. The efficacy end points were change from baseline in monthly migraine days, monthly acute migraine medication days, and patient-reported health-related quality of life.

At the start of the double-blind trial, patients had 8.7 days per month with a migraine. By the end of the 5-year open-label follow-up, patients had maintained a mean decrease from a baseline of 5.3 migraine days per month. The reduction in migraine frequency in the placebo group was evident starting 4 weeks after they were switched to erenumab and was sustained through the open-label trial for both original groups. During the last 4 weeks of the trial, more than one-third of patients had a complete absence of migraine days and 71% had ≥50% reduction in migraine days. Similarly, both headache severity and the use of acute migraine therapies declined over the 5 years while quality-of-life scores improved.

The investigators did not detect any new safety issues, and rates of adverse events during the 5-year follow-up were not higher than during the double-blind trial. The exposure-adjusted incidence rate of serious adverse events was not higher in patients taking erenumab compared with the placebo group during the double-blind study. Most serious adverse events occurred once in 1 to 3 patients with no discernible pattern. The treatment discontinuation rate for adverse events was 5%. The mean increase in blood pressure was 2 to 3 mm Hg from baseline to 5 years.

Approximately 10% of patients tested positive for antibodies against erenumab at some point during the trial; of these, 77% tested negative by the end of the trial.

The investigators concluded that erenumab caused long-term clinically meaningful improvements in migraine frequency and severity and had a positive impact on migraine-related quality of life with no new safety concerns.

“This analysis represents the longest-term efficacy and safety data of a CGRP pathway antibody to date. Overall, retention rates, efficacy, patient-reported outcomes, and safety results support the use of erenumab as a preventive treatment for patients with [episodic migraine],” the investigators wrote.


Ashina M, Goadsby PJ, Reuter U, et al. Long-term efficacy and safety of erenumab in migraine prevention: results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. 2021;28:1716-1725.

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