New 5-Year Data Highlight Erenumab’s Efficacy, Safety

Erenumab treatment for migraine was associated with reductions in migraine frequency and improvements in health-related quality of life that were maintained for at least 5 years, according to the results of an open-label treatment phase (OLTP) of a recent study published in European Journal of Neurology.

Erenumab, a monoclonal antibody, was approved by the FDA in 2018 and is administered monthly via self-injection of a 70- or 140-mg dose. The treatment blocks the calcitonin gene-related peptide receptor, which is believed to play a crucial role in migraine.

Although previous studies have demonstrated erenumab’s clinical benefits over the course of 3 and 12 months, little is known about the treatment’s long-term impact. “Since migraine is often a lifelong disorder, patients may require treatment for many years,” the researchers wrote. “Thus, migraine preventive treatments require favorable long-term benefit-risk profiles.”

The current study assessed safety and efficacy data after a 5-year OLTP following a 12-week double-blind treatment phase (DBTP). Participants in the DBTP all had episodic migraine (EM) and received either placebo or erenumab (7, 21, or 70 mg) every 4 weeks. In comparison, participants in the OLTP received treatment every 4 weeks at an initial dose of 70 mg but increasing to 140 mg following a protocol amendment.

Efficacy data, including changes in monthly migraine days (MMD), acute migraine-specific medication (AMSM) days, and health-related quality of life were collected via electronic diary entries. Data from the Headache Impact Test, Migraine-Specific Quality-of-Life Questionnaire, and Migraine Disability Assessment were also assessed.

In addition, adverse events (AEs), vital signs, and development of anti-erenumab antibodies were monitored to evaluate safety and tolerability over 5 years.

A total of 383 migraineurs were enrolled in the OLTP, while “erenumab treatment was discontinued by 132 patients before the dose increase and by 36 patients while receiving 140 mg after the dose increase.” Most discontinuations were driven by patient request, the researchers noted. The OLTP was completed by patients.

Analyses revealed:

• Mean (standard error [SE]) change in MMD from baseline of 8.7 (0.2) days was −5.3 (0.3) days; an average reduction of 62.3% at year 5
• Among patients using AMSM at baseline (6.3 [2.8] treatment days), the mean change in monthly AMSM days was −4.4 (0.3) days at the end of 5 years
• Patient-reported outcomes indicated stable improvements in disability, headache impact, and migraine-specific quality of life
• Exposure-adjusted patient incidence rates of AEs were 123.0/100 patient-years; most frequently, nasopharyngitis, upper respiratory tract infection, and influenza
• Constipation did not increase after the parent study, and overall rates were lower than those reported in the pooled, double-blind, placebo-controlled analysis (1.8 vs 7.0/100 patient-years)
• Serious AEs reported by 49 patients (3.8/100 patient-years) were mostly single occurrence
• 2 fatalities were reported, but assessed as unrelated to erenumab
• There were no increases in incidence of AEs, serious AEs, or AEs leading to treatment discontinuation over 5 years of exposure

The researchers also found no meaningful changes in mean systolic/diastolic blood pressure or heart rate through the end of study after safety follow-up. Additionally, only a small subset of patients was found to have neutralizing antibodies.

“Erenumab treatment resulted in long-term durable, clinical improvements including reduction in MMD and AMSM use, and stable improvements in disability, headache impact, and migraine-specific quality of life,” the authors wrote.

The reduction of migraine frequency can have significant economic and social impacts,as current estimates value migraine’s total economic impact on the United States between $13 billion and $17 billion annually.

“Overall, retention rates, efficacy, patient-reported outcomes, and safety results support the use of erenumab as a preventive treatment for patients with EM,” the researchers concluded. “Ongoing comparative clinical studies and postmarketing surveillance will provide further information on the benefit-risk profile in real-world settings.”

Reference

Ashina M, Goadsby PJ, Reuter U, et al. Long-term efficacy and safety or erenumab in migraine prevention: results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. Published online January 5, 2021. doi:10.1111/ene.14715