Early Erenumab Superior to Nonspecific Oral Preventives in Episodic Migraine

Compared with continuous oral migraine preventive medications (OMPMs), erenumab has greater efficacy, safety, and adherence in patients with episodic migraine, according to study results published in JAMA Neurology.

In a 12-month prospective, international, multicenter, phase 4 randomized controlled trial (APPRAISE; ClinicalTrials.gov Identifier: NCT03927144), researchers compared the safety and efficacy of erenumab and OMPMs in patients with episodic migraine with an inadequate response to previous preventive treatments.

The study included 3 phases: screening (up to 2 weeks), baseline (4 weeks), and open-label treatment (52 weeks). Participants included in the analysis were adults with a history of migraine for at least 12 months and symptoms for 4 or more days per month, with an inadequate response to other migraine preventive treatments in the previous 6 months.

Eligible participants were randomly assigned 2:1 to receive 70 or 140 mg erenumab or OMPMs.

Primary study endpoint was percentage of patients who had a 50% or greater reduction in monthly migraine days from baseline to 12 months. Secondary endpoints included percentage of patients who completed the treatment; mean change in migraine days from baseline during the treatment period; and percentage of patients with a change in clinical status, measured using the Patients’ Global Impression of Change (PGIC) scale. The researchers collected outcomes using an electronic diary.

Of 866 patients identified for the study, 621 (mean age, 41.3; 87.8% women; 98.9% White) were eligible for inclusion. Of these patients, 433 (66.5%) received erenumab and 208 (33.5%) received OMPMs. 

A total of 523 of the 621 patients (84.2%) completed the 12-month treatment phase, of whom 91.3% and 70.2% were receiving erenumab and OMPMs, respectively.

At 12 months, significantly more patients who received erenumab vs OMPMs had at least a 50% reduction in migraine days per month (56.2% vs 16.8%; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). In addition, a higher percentage of patients receiving erenumab vs OMPMs completed their initial treatment (86.9% vs 37.5%; OR, 11.27; 95% CI, 7.53-16.87; P <.001).

Mean changes from baseline to month 12 in average monthly migraine days were significantly greater with erenumab vs OMPMs (month 12: adjusted mean migraine days, -4.32 vs -2.65 days; treatment difference, -1.67 days; P <.001).

More patients who received erenumab vs OMPMs were responders on the PGIC scale (76.0% vs 18.8%; OR, 13.75; 95% CI, 9.08-20.83; P <.001).

For treatment-emergent adverse events, patients who received erenumab vs OMPMs had 30% lower exposure-adjusted rates (r=189.3 vs 267.2 per 100 patient-years). The most common adverse events were constipation and injection site pain with erenumab, and fatigue and weight gain with OMPMs.

Study limitations included the use of only locally approved and marketed OMPMs and the open-label design that may have resulted in a placebo response in some patients.

“These findings lend further support to the recent guideline update issued by the European Headache Federation, in which CGRP targeted mAbs [monoclonal antibodies] are considered as a first-line treatment option for patients with migraine who require preventive treatment,” the researchers concluded.

Disclosure: This research was supported by Novartis Pharma AG, Basel, Switzerland. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.