PDF: Fremanezumab for Episodic Migraine
(2018)Objective
Fremanezumab - To assess the efficacy of monthly and single higher-dose (quarterly-equivalent) subcutaneous fremanezumab compared with placebo for the prevention of episodic migraine.
Study Summary
• Over 12 weeks, patients received either monthly subcutaneous fremanezumab (225 mg), a single higher dose of fremanezumab (675 mg at baseline), or placebo.
• Both fremanezumab regimens significantly reduced the mean number of monthly migraine days compared to placebo.
• The mean reduction versus placebo was 1.5 days/month for the monthly dose and 1.3 days/month for the single higher dose. The treatment was well-tolerated, with injection site reactions being the most common adverse event.
Intervention
A 12-week course of subcutaneous treatment with either fremanezumab 225 mg monthly, fremanezumab 675 mg as a single baseline dose, or matching placebo injections.
Study Design
Arms: Array
Outcome
• The rate of achieving a 50% or greater reduction in migraine days was significantly higher with both monthly dosing (47.7%) and single higher dosing (44.4%) compared to placebo (27.9%).
• Injection site reactions were the most common adverse events and were more frequent in the fremanezumab groups.
Bottom Line
In patients with episodic migraine who had not previously failed multiple medication classes, both monthly and single higher-dose (quarterly-equivalent) subcutaneous fremanezumab resulted in a statistically significant reduction in the mean number of monthly migraine days over a 12-week period compared with placebo. The treatment was well tolerated.
Major Points
- This was a large, randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries.
- 875 patients with episodic migraine (6-14 headache days per month) were randomized 1:1:1 to receive either monthly fremanezumab (225 mg), a single higher dose (675 mg at baseline only), or placebo for 12 weeks.
- The primary endpoint was the mean change from baseline in the average number of monthly migraine days over the 12-week treatment period.
- Both fremanezumab groups met the primary endpoint. The monthly dosing group had a mean reduction of 3.7 migraine days, and the single higher-dose group had a reduction of 3.4 days, compared to a 2.2-day reduction in the placebo group.
- The mean difference versus placebo was a reduction of 1.5 days for the monthly dose and 1.3 days for the single higher dose (both P<.001).
- Adverse events were mostly mild to moderate, with injection site reactions being the most common events reported more frequently in the fremanezumab groups.
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled, parallel-group trial
- Randomization
- Yes
- Blinding
- Double-blind (patients, investigators, and sponsor personnel were blinded)
- Sample Size
- 875
- Follow-up
- 12 weeks
- Centers
- 123
- Countries
- 9 countries
Primary Outcome
Definition: Mean change from baseline in the mean number of monthly migraine days during the 12-week period after the first dose.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| -2.2 days | -3.7 days (monthly dosing); -3.4 days (single higher dose) | - (-2.01 to -0.93 (monthly vs placebo); -1.79 to -0.72 (single dose vs placebo)) | <.001 (for both comparisons vs placebo) |
Limitations & Criticisms
- The trial was limited to a short-term follow-up of 3 months.
- The study did not include treatment-refractory patients (those who had failed 2 or more preventive drug classes).
- The trial did not compare fremanezumab with other active preventive treatments.
- A minimal clinically important difference for the primary outcome measure in episodic migraine has not been established.
Citation
JAMA. 2018;319(19):1999-2008.