Dr Jan Lewis BrandesJan Lewis Brandes, MD, MS
New findings from the phase 3 HALO development program has suggested that fremanezumab (Ajovy; Teva Pharmaceuticals) use in the treatment of migraine can reduce the need for acute headache medications.1

Ultimately, in the 865-patient analysis, the anti-calcitonin gene-related peptide (CGRP) agent reduced the use of migraine-specific headache medication, migraine-associated symptoms, and any acute headache medication use compared to placebo. The study authors included Jan Lewis Brandes, MD, MS, founder, Nashville Neuroscience Group, and assistant clinical professor of neurology, Vanderbilt University School of Medicine.

“Results here demonstrated that fremanezumab treatment decreased the need for acute headache medication use, particularly migraine-specific acute headache medication use. This may result in many potential benefits, as use of both acute headache medications and migraine-specific acute headache medications is associated with the development of medication overuse resulting in progression to chronic migraine, systemic AEs, loss of effectiveness over time, anxiety related to limited availability, and high costs,” Lewis Brandes and colleagues wrote.

Of the 865 patients included in the analysis, 287 were randomized to monthly fremanezumab (225 mg at baseline and weeks 4 and 8), 288 to quarterly fremanezumab (675 mg at baseline, placebo at weeks 4 and 8), and 290 to placebo. At baseline, the mean number of days with any acute medication use was 7.7 (±3.4), 7.8 (±3.7), and 7.7 (±3.6) for the monthly, quarterly, and placebo groups, respectively. Mean days with migraine-specific acute medication use were 6.1 (±3.1), 6.6 (± 3.1), and 7.1 (±3.0), respectively.

Fremanezumab use reduced the number of days with acute medication use by 1.4 (95% CI, –1.84 to –0.89; P <.001) for the monthly group and 1.3 (95% CI, –1.76 to –0.82; P <.001) for the quarterly group. Migraine-specific acute medication use was reduced by 2.2 days (95% CI, –2.80 to –1.56; P <.001) for the monthly group and 2.2 days (95% CI, –2.81 to –1.58; P <.001) for the quarterly group compared to placebo.

Similarly, the treatment groups experienced decreases in a number of symptoms, including nausea or vomiting—which occurred 4.5 (±3.6), 4.9 (±3.7), and 4.5 (±3.3) days for the monthly, quarterly, and placebo groups, respectively, at baseline—and photophobia and phonophobia—which occurred 5.5 (±4.1), 6.3 (±4.1), and 6.0 (±3.9)  days, respectively, at baseline.

The monthly average number of days with nausea or vomiting for the monthly group  was reduced to 2.1 (±0.19) days for a difference compared to placebo of 0.7 (95% CI, 1.12 to 0.29; P <.001), and for the quarterly group reduced to 1.9 (±0.19) days, for a difference versus placebo of 0.5 (95% CI, 0.87 to 0.04; P = .031).

Significant reductions from baseline were also observed in the monthly average number of days with photophobia the monthly (3.0 ±0.23 days; difference, 0.9 [95% CI, 1.43 to 0.45]; P <.001) and quarterly (2.8 ±0.23 days; difference, 0.8 [95% CI, 1.27 to 0.29], P = .002) groups compared with placebo. Phonophobia was reduced for the monthly group (3.0 ±0.22 days; difference, 1.0 [95% CI, 1.45 to 0.49]; P <.001) and the quarterly group (2.7 ±0.22 days; difference, 0.6 [95% CI, 1.12 to 0.16]; P = .009) compared to placebo.

“These reductions in associated features of migraine support the primary efficacy findings and further suggest that fremanezumab may improve patient outcomes, as both the headache and associated non-headache symptoms of migraine are reduced,” Lewis Brandes and colleagues wrote. “Given that nausea is a common and debilitating symptom associated with an increased risk of progression from episodic to chronic migraine, the improvements in nausea or vomiting seen with fremanezumab treatment may be particularly consequential.”

Lewis Brandes et al. identified a pair of limitations of the study: that this was prespecified secondary and exploratory analyses of the HALO EM trial, and that the migraine-associated outcomes and symptoms assessed (acute headache medication use, nausea) are associative rather than causative.
Brandes JL, Kudrow D, Yeung PP, et al. Effects of fremanezumab on the use of acute headache medication and associated symptoms of migraine in patients with episodic migraine. Cephalagia. Published online November 26, 2019. Accessed November 26, 2019. doi: 10.1177/0333102419885905.