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Background: Fremanezumab, 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. Methods: This 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]). Results: Data 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. Conclusions: In 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). [ABSTRACT FROM AUTHOR]

The article presents the discussion on Fremanezumab in individuals with chronic migraine showing inadequate response to onabotulinumtoxin A and topiramate or valproic acid. Topics include Fremanezumab, a humanized monoclonal antibody (IgG2Δa) selectively target calcitonin gene-related peptide; and treatment-by-subgroup interactions being assessed using an analysis of covariance model for the efficacy outcomes.

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression. Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene–related peptide, has been approved for the preventive treatment of migraine in adults. CM and depression are highly comorbid. Methods: The 12‐week, Phase 3 HALO trial randomized patients with CM to fremanezumab quarterly (675 mg/placebo/placebo), fremanezumab monthly (675/225/225 mg), or placebo. Post hoc analyses evaluated the effects of fremanezumab in patients with moderate to severe depression (baseline 9‐item Patient Health Questionnaire sum score ≥10) on monthly number of headache days of at least moderate severity; monthly migraine days; Patient Global Impression of Change (PGIC); 6‐item Headache Impact Test (HIT‐6) scores; and depression. Results: For the 219/1121 (19.5%) patients with moderate to severe depression at baseline, fremanezumab was associated with a significant reduction in monthly number of headache days of at least moderate severity for active treatment versus placebo (least‐squares mean change ± standard error for quarterly dosing: −5.3 ± 0.77; for monthly dosing: −5.5 ± 0.72; and for placebo: −2.2 ± 0.81; both p < 0.001). More patients achieved a ≥50% reduction in headache days of at least moderate severity with fremanezumab (quarterly: 31/78 [39.7%]; monthly: 39/96 [40.6%]) than placebo (9/67 [13.4%]; both p < 0.001). Compared with placebo, fremanezumab improved PGIC and HIT‐6 scores. Conclusions: Fremanezumab demonstrated efficacy in the preventive treatment of CM and reduced headache impact in patients with comorbid depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]