Abstract
BackgroundThe FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes.MethodsOverall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12 weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12 weeks of double-blind treatment, evaluated by country in these subgroup analyses.ResultsOf 14 countries contributing data, the Czech Republic (n = 188/838; 22%), the United States (n = 120/838; 14%), and Finland (n = 85/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12 weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, − 1.9 [− 3.25, − 0.47]; P = 0.009; monthly fremanezumab, − 3.0 [− 4.39, − 1.59]; P < 0.001), the United States (quarterly fremanezumab, − 3.7 [− 5.77, − 1.58]; P < 0.001; monthly fremanezumab, − 4.2 [− 6.23, − 2.13]; P < 0.001), and Finland (quarterly fremanezumab, − 3.0 [− 5.32, − 0.63]; P = 0.014; monthly fremanezumab, − 3.9 [− 6.27, − 1.44]; P = 0.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from – 5.6 to – 2.4 with quarterly fremanezumab and from − 5.3 to − 1.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups.ConclusionsMonthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes.Trial registrationClinicalTrials.gov Identifier: NCT03308968.
Highlights
Methods838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites
The FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, for patients with difficult-to-treat migraine
Based on the favorable efficacy results demonstrated in the overall study population, we hypothesized that treatment with quarterly or monthly fremanezumab would be efficacious in patients regardless of their country of residence
Summary
This was a preplanned exploratory analysis (for the primary endpoint) of the international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS study (ClinicalTrials.gov Identifier: NCT03308968) in patients with EM or CM who had documented inadequate response to 2 to 4 prior classes of migraine preventive medications [10]. The primary efficacy outcome for the FOCUS study was the mean change from baseline in the monthly average number of migraine days over 12 weeks of double-blind treatment. Efficacy analyses were performed on the modified intention-to-treat analysis set, which included all randomized patients who received ≥ 1 dose of study drug and had ≥ 10 days of post-baseline efficacy assessments for the primary endpoint. For the change from baseline in the monthly average number of migraine days during 12 weeks (primary endpoint of the study), analyses were performed using an analysis of covariance (ANCOVA) method that included treatment, sex, region, special group of treatment failure (patients who had documented inadequate response to valproic acid and documented inadequate response to 2 to 3 other migraine preventive medication classes), migraine classification, and treatment-by-migraine classification interaction as fixed effects and baseline number of migraine days and years since onset of migraine as covariates. Statistical analyses for additional efficacy outcomes are described within the eMethods in the Supplement
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