Dataset Information

Reduction in the severity and duration of headache following fremanezumab treatment in patients with episodic and chronic migraine.

ABSTRACT:

Objective

To evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM).

Background

Fremanezumab is a fully humanized monoclonal antibody (IgGΔa) that selectively targets calcitonin gene-related peptide and is efficacious in reducing migraine frequency.

Methods

This exploratory post hoc analysis included data from three randomized, double-blind, 12-week, phase 3 studies (HALO CM, HALO EM, and FOCUS). In all three studies, patients with CM or EM were randomized 1:1:1 to receive subcutaneous quarterly fremanezumab (month 1/2/3: 675 mg/placebo/placebo), monthly fremanezumab (month 1/2/3: 675 mg [CM], 225 mg [EM]/225 mg/225 mg), or matched monthly placebo. Changes from baseline were evaluated in the proportion of headache days of at least moderate severity, peak severity of headache days, mean monthly headache hours (of any severity and at least moderate severity), and mean headache hours per headache day of any severity.

Results

A total of 2843 patients were randomized with 2823 patients included in the efficacy analyses across all studies (HALO CM, N = 1121; HALO EM, N = 865; FOCUS, N = 837). At study baseline, mean (standard deviation [SD]) monthly number of headache days rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 13.2 (5.5), 12.8 (5.8), and 13.3 (5.8) in HALO CM; 7.2 (3.1), 6.8 (2.9), and 6.9 (3.1) in HALO EM; and 12.4 (5.8), 12.7 (5.8), and 12.8 (5.9) in FOCUS. Patients experienced significant least-squares mean (LSM; 95% confidence interval) percent reductions from baseline in monthly number of headache days rated moderate or severe during the 12 weeks: HALO CM, quarterly fremanezumab, 34.5% (-39.8, -29.2) and monthly fremanezumab, 36.2% (-41.4, -31.0) vs. placebo, 19.6% (-20.0, -14.3); HALO EM, quarterly fremanezumab, 40.7% (-47.8, -33.5) and monthly fremanezumab, 43.4% (-50.4, -36.3) vs. placebo, 17.9% (-24.9, -11.0); and FOCUS, quarterly fremanezumab, 36.5% (-41.9, -31.1) and monthly fremanezumab, 38.6% (-44.0, -33.3) vs. placebo, 3.5% (-8.9, 1.8); all p < 0.0001. At study baseline, mean (SD) number of monthly headache hours rated moderate or severe in the quarterly fremanezumab, monthly fremanezumab, and placebo groups, respectively, were 66.4 (58.8), 68.0 (53.9), and 68.5 (57.0) in HALO CM; 33.3 (25.4), 31.7 (23.7), and 31.6 (23.2) in HALO EM; and 59.2 (54.7), 64.3 (65.2), and 65.9 (70.2) in FOCUS. Significant reductions were observed in LSM (standard error) number of monthly headache hours of at least moderate severity: HALO CM, quarterly fremanezumab, 24.4 (2.5) and monthly fremanezumab, 26.4 (2.3) vs. placebo, 14.1 (2.5); HALO EM, quarterly fremanezumab, 14.5 (1.4) and monthly fremanezumab, 15.5 (1.3) vs. placebo, 8.1 (1.3); and FOCUS, quarterly fremanezumab, 16.8 (3.0) and monthly fremanezumab, 18.3 (3.0) vs. placebo, 2.3 (3.0); all p < 0.001.

Conclusion

These analyses demonstrated that quarterly or monthly treatment with fremanezumab significantly reduced headache severity and duration in patients with CM or EM, including in patients with documented inadequate response to two to four prior migraine preventive medication classes.

SUBMITTER: Ashina M

PROVIDER: S-EPMC8362007 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundGalcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine.MethodsThe episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4-14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18-65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed.ResultsGalcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days.ConclusionsGalcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine.Trial registrationNCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196 , (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

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Project description:BackgroundFremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab.MethodsEpisodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or ≥75% reduction in monthly migraine days were evaluated.ResultsOf the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: - 4.7 [5.4]; - 5.1 [4.7]; - 5.5 [5.0]), monthly headache days of at least moderate severity (- 4.5 [5.0]; - 4.8 [4.5]; - 5.2 [4.9]), days per month of acute headache medication use (- 4.3 [5.2]; - 4.9 [4.6]; - 4.8 [4.9]), days with photophobia/phonophobia (- 3.1 [5.3]; - 3.4 [5.3]; - 4.0 [5.2]), and days with nausea or vomiting (- 2.3 [4.6]; - 3.1 [4.5]; - 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%).ConclusionFremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes.Trial registrationClinicalTrials.gov NCT03308968 (FOCUS).