Fremanezumab May Reduce Medication Overuse in Migraineurs

SAN FRANCISCO—Treatment with fremanezumab is associated with reduced overuse of acute medications and a corresponding decrease in days on which a patient uses acute medications, according to a phase III study described at the 60th Annual Scientific Meeting of the American Headache Society.

The overuse of acute or symptomatic headache medications (eg, triptans, ergot derivatives, opioids, and combination analgesics) can cause medication overuse headache (MOH). Chronic migraine is often accompanied by MOH, and the prevention of MOH is one of the main goals in the preventive treatment of migraine.

Stephen D. Silberstein, MD

Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, reduced the frequency and severity of headaches in patients with chronic migraine who participated in clinical trials. Stephen D. Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues assessed the effect of fremanezumab, compared with placebo, on medication overuse and acute headache medication use in patients with chronic migraine.

Comparing Two Fremanezumab Doses With Placebo

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, phase III study, during which they randomized eligible patients with chronic migraine in equal groups to receive subcutaneous injections of fremanezumab quarterly dosing (ie, 675 mg at baseline and placebo at Weeks 4 and 8), fremanezumab monthly dosing (ie, 675 mg at baseline and 225 mg at Weeks 4 and 8), or placebo at each time point over a 12-week treatment period. Dr. Silberstein’s group defined medication overuse as the use of acute headache medication on 15 or more days, the use of migraine-specific acute medication on 10 or more days, or the use of combination medications for headache on 10 or more days during the 28-day baseline period.

In a post hoc analysis, the researchers assessed the proportion of patients who reverted from overusing medications at baseline to not overusing medications at Week 12, as well as the change from baseline in the number of days of acute headache medication use among these patients. Analyses were performed using data for all randomized patients who received at least one dose of study drug and had at least 10 days of postbaseline efficacy assessments on the primary end point.

Fremanezumab Was More Likely to Reduce Overuse

At baseline, the number of patients with medication overuse was 201 in the quarterly arm, 198 in the monthly arm, and 188 in the placebo arm. Among these participants, significantly more fremanezumab-treated patients reported no medication overuse during the 12-week treatment period. The number of patients reporting no medication overuse was 111 (55%) in the quarterly arm, 120 (61%) in the monthly arm, and 87 (46%) in the placebo arm. The investigators observed a response to treatment as early as Week 4 (102 [51%] quarterly patients, 107 [54%] monthly patients, and 73 [39%] controls).

Among the patients who responded to treatment over the 12-week treatment period, the baseline number of days with medication overuse was similar across treatment groups (approximately 16.6). Within this population, fremanezumab treatment significantly reduced the number of days of acute headache medication use over the 12-week treatment period by nine in the quarterly arm and 8.9 in the monthly arm, compared with 7.1 among controls.