The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study

Abstract

Background: We evaluated the efficacy of fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, in patients with chronic migraine (CM) with and without medication overuse (MO).

Methods: In a 12-week, phase 3 trial, patients with CM were randomized to fremanezumab quarterly (675 mg/placebo/placebo), monthly (675 mg/225 mg/225 mg), or placebo. Post hoc analyses assessed the impact of fremanezumab in patients with and without MO (monthly use of acute headache medication ≥15 days, migraine-specific acute medication ≥10 days, or combination medication ≥10 days) on efficacy outcomes, including headache days of at least moderate severity (HDs), and six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life (MSQoL) questionnaire scores.

Results: Of 1130 patients enrolled, 587 (51.9%) had baseline MO. Fremanezumab reduced placebo-adjusted least-squares mean (95% confidence interval) monthly HDs (- 2.2 [- 3.1 to - 1.2] and - 2.7 [- 3.7 to - 1.8]; P < 0.0001) in patients with MO and without MO (quarterly - 1.4 [- 2.3 to - 0.5], P = 0.0026; monthly - 1.4 [- 2.3 to - 0.6], P = 0.0017). Significantly more fremanezumab-treated patients had ≥ 50% reduction in HDs versus placebo, regardless of baseline MO (with: quarterly 70/201 [34.8%], monthly 78/198 [39.4%] vs placebo 26/188 [13.8%]; without: quarterly 71/174 [40.8%], monthly 75/177 [42.4%] vs placebo 41/183 [22.4%]). Fremanezumab improved HIT-6 and MSQoL scores. Significantly more fremanezumab-treated patients reverted to no MO (quarterly 111/201 [55.2%], monthly 120/198 [60.6%]) versus placebo (87/188 [46.3%]).

Conclusions: Fremanezumab is effective for prevention of migraine in patients with CM, regardless of MO, and demonstrated a benefit over placebo in reducing MO.

Trial registration: ClinicalTrials.gov NCT02621931 (HALO CM), registered December 12, 2012.

Keywords: Chronic migraine; Fremanezumab; Medication overuse.

Conflict of interest statement

SDS provides consultation to Abide Therapeutics, Allergan, Amgen, Avanir, Biohaven, Cefaly, Curelator, Inc., Dr. Reddy’s Laboratories, Egalet Corporation, GlaxoSmithKline Consumer Health Holdings, LLC, eNeura Inc., electroCore Medical, LLC, Impel NeuroPharma, Inc., Lilly USA, LLC, Medscape, LLC, Novartis, Inc., Satsuma Pharmaceuticals, Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, Theranica, and Trigemina, Inc. JMC, MJS, and RY are employees of Teva Branded Pharmaceutical Products R&D, Inc. (USA). SA provides consultation for Allergan, Amgen, Promius, Supernus, and Novartis. ZK provides consultation to Allergan, Novartis, Eli Lilly, and Teva Pharmaceuticals.

Figures

Fig. 1

Change in days with (a) headache, (b) migraine, and (c) medication use in patients with CM by MO. Values shown are the mean changes from baseline in the monthly average number of (a) headache days of at least moderate severity, (b) migraine days, and (c) acute headache medication use during the 12-week treatment period with and without MO. CM, chronic migraine; LSM, least-squares mean; MO, medication overuse; SE, standard error

Fig. 2

Proportion of patients with CM with ≥ 50% response (a) with MO and (b) without MO. A ≥ 50% response was defined as ≥ 50% reduction from baseline in the monthly average number of headache days of at least moderate severity over 12 weeks. CM, chronic migraine; MO, medication overuse

Fig. 3

Proportion of patients with CM who reverted from MO to no MO during the 12-week treatment period. CM, chronic migraine; MO, medication overuse

Fig. 4

(a) Reduction in medication use and (b) ≥ 50% response in patients with CM by reversion to no MO. Values shown in part A are mean (SE) change from baseline over 12 weeks in the monthly average number of days of acute medication use in patients who reverted from MO to no MO (blue bars) and in those who did not revert from MO to no MO (green bars). Values shown in part B are the proportions of patients with a ≥ 50% response, defined as a ≥ 50% reduction in the monthly average number of headache days of at least moderate severity from baseline over 12 weeks, in patients who reverted from MO to no MO (blue bars) and in those who did not revert from MO to no MO (green bars). CM = chronic migraine; MO = medication overuse; SE = standard error