Dataset Information

Improvements in quality of life and work productivity with up to 6 months of fremanezumab treatment in patients with episodic and chronic migraine and documented inadequate response to 2 to 4 classes of migraine-preventive medications in the phase 3b FOCUS study.

ABSTRACT:

Background

Migraine is associated with depression as well as negative impact on quality of life and work productivity. Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa), selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine.

Objective

In this open-label extension (OLE) of the phase 3b FOCUS study, we assessed patient-reported outcomes (PROs) over time.

Methods

Patients with episodic migraine (EM) and chronic migraine (CM) completing the 12-week, double-blind (DB) period of the FOCUS trial entered the 12-week OLE and received three monthly doses of fremanezumab (225 mg). PROs included the Migraine-Specific Quality of Life (MSQoL) questionnaire (role function-restrictive [RFR], role function-preventive [RFP], and emotional function [EF] domains), EuroQol-5-Dimension-5-Level (EQ-5D-5L) questionnaire, Patient Global Impression of Change (PGIC) assessment, Work Productivity and Activity Impairment (WPAI) questionnaire, and 9-Item Patient Health Questionnaire (PHQ-9).

Results

A total of 838 patients were randomized in the DB period, 807 entered the OLE at 3 months, and 772 were still enrolled at 6 months. At 6 months, patients in the quarterly fremanezumab, monthly fremanezumab, and placebo DB randomization groups, respectively, reported improvements in RFR (mean [standard deviation] change from baseline: 24.6 [21.9]; 22.9 [21.3]; 20.8 [26.5]), RFP (19.6 [20.0]; 18.3 [19.7]; 16.0 [19.9]), and EF (22.5 [24.2]; 19.1 [23.6]; 17.2 [24.7]) domains of the MSQoL questionnaire, the EQ-5D-5L questionnaire (8.0 [19.6]; 7.3 [21.1]; 6.6 [21.0]), all four domains of the WPAI questionnaire, and the PHQ-9 (-2.4 [5.3]; -1.6 [5.5]; -2.0 [4.9]); 77.1% (209/271), 75.4% (205/272), and 68.8% (181/263) of patients were identified as PGIC responders.

Conclusion

Among patients with EM or CM and prior inadequate response to multiple migraine-preventive medication classes, progressive improvements in MSQoL, depression, and work productivity were achieved during 6 months of fremanezumab treatment.

SUBMITTER: Spierings ELH

PROVIDER: S-EPMC8597120 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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).

Project description:ObjectiveTo evaluate fremanezumab quarterly or monthly vs placebo on health-related quality of life, health status, patients' global impression of change, and productivity in patients with chronic migraine (CM).MethodsHALO CM was a double-blind, placebo-controlled trial in patients with CM. Patients were randomized 1:1:1 to treatment with fremanezumab quarterly (675 mg at baseline, placebo at weeks 4 and 8), fremanezumab monthly (225 mg at baseline, weeks 4 and 8), or placebo. This article assessed the effect of treatment with fremanezumab on health-related quality of life and productivity using the following prespecified assessments: the Migraine-Specific Quality of Life (MSQoL) questionnaire at baseline and weeks 4, 8, and 12; Patient Global Impression of Change (PGIC) questionnaire at weeks 4, 8, and 12; and EuroQoL 5-dimension, 5-response level (EQ-5D-5L) questionnaire and Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire at baseline and week 12.ResultsThe full analysis set included 1,121 patients: 375 patients with quarterly dosing, 375 with monthly dosing, and 371 with placebo. Fremanezumab quarterly and monthly was associated with significant improvements over placebo in change from baseline mean scores in MSQoL domains (all, p < 0.05) to week 12. At week 12, fremanezumab also showed significant improvements in EQ-5D-5L visual analog scale (p < 0.05) and PGIC scores (p < 0.0001) as well as significant reductions from baseline in WPAI:GH scores (p < 0.01) and presenteeism (impairment while working; p < 0.05) vs placebo.ConclusionsFremanezumab quarterly or monthly was associated with improvement over placebo in migraine-specific quality of life, overall health status, patients' global impression of change with treatment, and productivity in patients with CM.Clinicaltrialsgov identifierNCT02621931.Classification of evidenceThis study provides Class II evidence that in patients with CM, treatment with fremanezumab quarterly or monthly is associated with improvements in health-related quality of life and productivity.

Project description:ImportanceFremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine.ObjectiveTo assess the efficacy of fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose.Design and settingRandomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12.ParticipantsStudy participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded.InterventionsPatients were randomized 1:1:1 to receive subcutaneous monthly dosing of fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8).Main outcomes and measuresThe primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose.ResultsAmong 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of -1.5 days (95% CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of -1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2).Conclusions and relevanceAmong patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy.Trial registrationclinicaltrials.gov Identifier: NCT02629861.

Project description:BackgroundFremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings.MethodsThis retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway-targeted mAb [CGRP mAb]).ResultsData were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were - 7.7 (77.0%) in EM patients, - 10.1 (68.7%) in CM patients, - 10.8 (80.6%) in the MO subgroup, - 9.9 (68.3%) in the MDD subgroup, - 9.5 (66.4%) in the GAD subgroup, and - 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively.ConclusionsIn this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

Project description:ObjectiveTo evaluate the impact of fremanezumab on the severity and duration of remaining migraine attacks in patients with chronic migraine (CM) or episodic migraine (EM).BackgroundFremanezumab is a fully humanized monoclonal antibody (IgGΔa) that selectively targets calcitonin gene-related peptide and is efficacious in reducing migraine frequency.MethodsThis 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.ResultsA 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.ConclusionThese 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.