Biologics for episodic and chronic migraines

Clinical question

What is the efficacy of calcitonin gene-related peptide (CGRP) inhibitors in migraine prophylaxis?

Bottom line

Treating 5 to 8 patients with CGRP inhibitors will lead to 1 patient having at least a 50% reduction in monthly migraine days (MMD) compared with placebo. From baseline, a decrease of 1 to 2 MMD may be seen. Cost may limit use.

Evidence

Results are statistically significant unless noted.

• A systematic review (5 RCTs, 2928 patients, about 9 to 18 MMD, 84% female)¹ of patients treated with either 70 mg or 140 mg of subcutaneous erenumab monthly for 12 weeks: more patients in the 70-mg dose group achieved at least a 50% reduction in MMD compared with the placebo group (42% vs 27%; number needed to treat [NNT] = 7). Similar results were found in the 140-mg dose group versus the placebo group (40% vs 21%; NNT = 5). A reduction of 1.5 to 2.0 MMD was found.

• A systematic review (3 RCTs, 2886 patients, about 9 to 19 MMD, 85% female)² of patients treated with 120 mg or 240 mg of subcutaneous galcanezumab monthly for 12 to 24 weeks: about 41% of patients in both the 120-mg and 240-mg dose groups achieved at least a 50% reduction in MMD compared with 26% in the placebo group (NNT = 7). A reduction of 1.9 MMD was found.

• In 5 RCTs (3379 patients, about 16 MMD)³ of patients treated with 675 mg of subcutaneous fremanezumab every 3 months: more patients in the treatment group achieved at least a 50% reduction in MMD compared with the placebo group (41% vs 19%; NNT = 5). A reduction of 2.2 MMD was found.

• Another systematic review had similar findings.⁴

• Adverse events: There was no difference except for injection site pain (11% vs 8% with placebo).^1,2,4

• Limitations: These were industry-sponsored studies of short duration (12 to 24 weeks); long-term efficacy and safety are unknown. Trials often excluded patients for whom more than 2 to 3 medication groups failed.

Context

• Other medications achieving more than a 50% reduction in MMD include propranolol (NNT = 4)⁵ and tricyclic antidepressants (NNT = 5).⁶ Candesartan (about 1.5 days) and topiramate (about 1.0 day) have shown headache frequency reduction versus placebo.^5,7

• In Canada, CGRP inhibitors cost about $ 7000 per year.⁸

• Guidelines⁹ recommend a trial of at least 2 oral agents before prescribing CGRP inhibitors.

Implementation

Clinicians may start prophylactic medications if acute treatments are ineffective, or if headache frequency is more than 8 days per month despite use of acute treatments.¹⁰ Guidelines have recommended that oral prophylactic medication such as propranolol, amitriptyline, and nortriptyline are generally trialed before other interventions (eg, onabotulinumtoxinA injections).¹⁰ Migraine triggers can include alcohol, caffeine overuse, diet, smoking, and vasodilating antihypertensives.¹¹ Tools to track and monitor migraines include the Canadian Migraine Tracker and the Migraine Buddy app.^12,13