User login
LOS ANGELES—Fremanezumab, a fully humanized monoclonal antibody, is a safe and effective therapy for the preventive treatment of chronic migraine, according to phase III data presented at the 70th Annual Meeting of the American Academy of Neurology. The treatment also has a flexible dosing profile.
Monthly and Quarterly Dosing Regimens
Fremanezumab selectively targets the calcitonin gene-related peptide ligand and is administered through subcutaneous injections. Stephen Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate two subcutaneous dose regimens of fremanezumab for the prevention of chronic migraine. Eligible patients were between ages 18 and 70. Exclusion criteria included use of onabotulinumtoxinA in the four months before screening, use of opioids or barbiturates for more than four days during the pretreatment period, and failure of two or more prior preventive medicines. 
The investigators assigned 1,130 participants to one of three treatment arms. The first (monthly dosing) arm received 675 mg of fremanuzemab during the first month, followed by 225 mg of fremanezumab at months two and three. The second (quarterly dosing) arm received 675 mg of fremanezumab at month one, followed by placebo injections at months two and three. The third arm received monthly administration of matching placebo. The study’s primary efficacy end point was the mean change in the monthly average number of headache days of at least moderate severity from baseline (ie, a 28-day pretreatment period) to the 12-week double-blind treatment period. Dr. Silberstein and colleagues evaluated this end point using an analysis of covariance method or the Wilcoxon rank sum test.
During the 28-day baseline period, participants’ mean number of headache days of at least moderate severity was 13.1. During the 12-week period after the first dose, the number of monthly headache days of at least moderate severity decreased by 2.5 in the placebo arm, 4.6 in the monthly dosing arm, and 4.3 in the quarterly arm. The differences between the fremanezumab and placebo arms were statistically significant.
Secondary End Points Favored Fremanezumab
In addition, the number of monthly migraine days decreased significantly during the 12-week period after the first dose in the monthly dosing arm (by 5.0 from 16.0) and the quarterly dosing arm (by 4.9 from 16.2), compared with the placebo arm (by 3.2 from 16.3). The number of monthly migraine days also decreased significantly for both dosing regimens during the four weeks after the first dose.
Furthermore, 37.6% of patients in the quarterly dosing arm and 40.8% of patients in the monthly dosing arm had at least a 50% reduction in headache days of at least moderate severity, compared with 18.1% of the placebo arm. Similarly, 7.5% of patients in the quarterly dosing arm and 9.1% of patients in the monthly dosing arm had at least a 75% reduction in headache days of at least moderate severity, compared with 2.7% of the placebo arm.
Fremanezumab was associated with reductions in work productivity loss, compared with placebo. The change from baseline on the Work Productivity and Activity Impairment Questionnaire was −16.6 days in the quarterly dosing arm, −15.9 in the monthly dosing arm, and −9.1 in the placebo arm. In addition, mean score on the Headache Impact Test-6 decreased by 6.4 in the quarterly dosing arm, 6.8 in the monthly dosing arm, and 4.5 in the placebo arm.
The most common adverse event in the study was injection-site reaction. Discontinuation for adverse events was infrequent. Similar proportions of patients in each treatment group had at least one adverse event, and the frequency of these events was lower among controls.
“These results are consistent with [those of] the prior phase II trials in chronic migraine, with similar efficacy and similar treatment effects,” said Dr. Silberstein. Fremanezumab’s safety, tolerability, early onset of efficacy, and flexible dosing “may increase adherence and improve clinical outcomes for patients with migraine,” he concluded.
LOS ANGELES—Fremanezumab, a fully humanized monoclonal antibody, is a safe and effective therapy for the preventive treatment of chronic migraine, according to phase III data presented at the 70th Annual Meeting of the American Academy of Neurology. The treatment also has a flexible dosing profile.
Monthly and Quarterly Dosing Regimens
Fremanezumab selectively targets the calcitonin gene-related peptide ligand and is administered through subcutaneous injections. Stephen Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate two subcutaneous dose regimens of fremanezumab for the prevention of chronic migraine. Eligible patients were between ages 18 and 70. Exclusion criteria included use of onabotulinumtoxinA in the four months before screening, use of opioids or barbiturates for more than four days during the pretreatment period, and failure of two or more prior preventive medicines.
The investigators assigned 1,130 participants to one of three treatment arms. The first (monthly dosing) arm received 675 mg of fremanuzemab during the first month, followed by 225 mg of fremanezumab at months two and three. The second (quarterly dosing) arm received 675 mg of fremanezumab at month one, followed by placebo injections at months two and three. The third arm received monthly administration of matching placebo. The study’s primary efficacy end point was the mean change in the monthly average number of headache days of at least moderate severity from baseline (ie, a 28-day pretreatment period) to the 12-week double-blind treatment period. Dr. Silberstein and colleagues evaluated this end point using an analysis of covariance method or the Wilcoxon rank sum test.
During the 28-day baseline period, participants’ mean number of headache days of at least moderate severity was 13.1. During the 12-week period after the first dose, the number of monthly headache days of at least moderate severity decreased by 2.5 in the placebo arm, 4.6 in the monthly dosing arm, and 4.3 in the quarterly arm. The differences between the fremanezumab and placebo arms were statistically significant.
Secondary End Points Favored Fremanezumab
In addition, the number of monthly migraine days decreased significantly during the 12-week period after the first dose in the monthly dosing arm (by 5.0 from 16.0) and the quarterly dosing arm (by 4.9 from 16.2), compared with the placebo arm (by 3.2 from 16.3). The number of monthly migraine days also decreased significantly for both dosing regimens during the four weeks after the first dose.
Furthermore, 37.6% of patients in the quarterly dosing arm and 40.8% of patients in the monthly dosing arm had at least a 50% reduction in headache days of at least moderate severity, compared with 18.1% of the placebo arm. Similarly, 7.5% of patients in the quarterly dosing arm and 9.1% of patients in the monthly dosing arm had at least a 75% reduction in headache days of at least moderate severity, compared with 2.7% of the placebo arm.
Fremanezumab was associated with reductions in work productivity loss, compared with placebo. The change from baseline on the Work Productivity and Activity Impairment Questionnaire was −16.6 days in the quarterly dosing arm, −15.9 in the monthly dosing arm, and −9.1 in the placebo arm. In addition, mean score on the Headache Impact Test-6 decreased by 6.4 in the quarterly dosing arm, 6.8 in the monthly dosing arm, and 4.5 in the placebo arm.
The most common adverse event in the study was injection-site reaction. Discontinuation for adverse events was infrequent. Similar proportions of patients in each treatment group had at least one adverse event, and the frequency of these events was lower among controls.
“These results are consistent with [those of] the prior phase II trials in chronic migraine, with similar efficacy and similar treatment effects,” said Dr. Silberstein. Fremanezumab’s safety, tolerability, early onset of efficacy, and flexible dosing “may increase adherence and improve clinical outcomes for patients with migraine,” he concluded.
LOS ANGELES—Fremanezumab, a fully humanized monoclonal antibody, is a safe and effective therapy for the preventive treatment of chronic migraine, according to phase III data presented at the 70th Annual Meeting of the American Academy of Neurology. The treatment also has a flexible dosing profile.
Monthly and Quarterly Dosing Regimens
Fremanezumab selectively targets the calcitonin gene-related peptide ligand and is administered through subcutaneous injections. Stephen Silberstein, MD, Director of the Headache Center at Thomas Jefferson University Hospital in Philadelphia, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate two subcutaneous dose regimens of fremanezumab for the prevention of chronic migraine. Eligible patients were between ages 18 and 70. Exclusion criteria included use of onabotulinumtoxinA in the four months before screening, use of opioids or barbiturates for more than four days during the pretreatment period, and failure of two or more prior preventive medicines.
The investigators assigned 1,130 participants to one of three treatment arms. The first (monthly dosing) arm received 675 mg of fremanuzemab during the first month, followed by 225 mg of fremanezumab at months two and three. The second (quarterly dosing) arm received 675 mg of fremanezumab at month one, followed by placebo injections at months two and three. The third arm received monthly administration of matching placebo. The study’s primary efficacy end point was the mean change in the monthly average number of headache days of at least moderate severity from baseline (ie, a 28-day pretreatment period) to the 12-week double-blind treatment period. Dr. Silberstein and colleagues evaluated this end point using an analysis of covariance method or the Wilcoxon rank sum test.
During the 28-day baseline period, participants’ mean number of headache days of at least moderate severity was 13.1. During the 12-week period after the first dose, the number of monthly headache days of at least moderate severity decreased by 2.5 in the placebo arm, 4.6 in the monthly dosing arm, and 4.3 in the quarterly arm. The differences between the fremanezumab and placebo arms were statistically significant.
Secondary End Points Favored Fremanezumab
In addition, the number of monthly migraine days decreased significantly during the 12-week period after the first dose in the monthly dosing arm (by 5.0 from 16.0) and the quarterly dosing arm (by 4.9 from 16.2), compared with the placebo arm (by 3.2 from 16.3). The number of monthly migraine days also decreased significantly for both dosing regimens during the four weeks after the first dose.
Furthermore, 37.6% of patients in the quarterly dosing arm and 40.8% of patients in the monthly dosing arm had at least a 50% reduction in headache days of at least moderate severity, compared with 18.1% of the placebo arm. Similarly, 7.5% of patients in the quarterly dosing arm and 9.1% of patients in the monthly dosing arm had at least a 75% reduction in headache days of at least moderate severity, compared with 2.7% of the placebo arm.
Fremanezumab was associated with reductions in work productivity loss, compared with placebo. The change from baseline on the Work Productivity and Activity Impairment Questionnaire was −16.6 days in the quarterly dosing arm, −15.9 in the monthly dosing arm, and −9.1 in the placebo arm. In addition, mean score on the Headache Impact Test-6 decreased by 6.4 in the quarterly dosing arm, 6.8 in the monthly dosing arm, and 4.5 in the placebo arm.
The most common adverse event in the study was injection-site reaction. Discontinuation for adverse events was infrequent. Similar proportions of patients in each treatment group had at least one adverse event, and the frequency of these events was lower among controls.
“These results are consistent with [those of] the prior phase II trials in chronic migraine, with similar efficacy and similar treatment effects,” said Dr. Silberstein. Fremanezumab’s safety, tolerability, early onset of efficacy, and flexible dosing “may increase adherence and improve clinical outcomes for patients with migraine,” he concluded.