The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study.
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ABSTRACT:
SUBMITTER: Silberstein SD
PROVIDER: S-EPMC7507645 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study.
Silberstein Stephen D SD Cohen Joshua M JM Seminerio Michael J MJ Yang Ronghua R Ashina Sait S Katsarava Zaza Z
The journal of headache and pain 20200921 1
<h4>Background</h4>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).<h4>Methods</h4>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 (m ...[more]
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Project description:ObjectiveTo evaluate the efficacy of fremanezumab in patients with chronic migraine (CM) and moderate to severe depression.BackgroundFremanezumab, 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.MethodsThe 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.ResultsFor 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.ConclusionsFremanezumab demonstrated efficacy in the preventive treatment of CM and reduced headache impact in patients with comorbid depression.
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Project description:BackgroundMigraine preventive medications are used to reduce headache frequency, severity, and duration. In patients with chronic migraine (CM), reversion to episodic migraine (EM) is an important treatment goal.ObjectiveTo evaluate the effect of fremanezumab on the rate of reversion from CM to EM.MethodsThis phase 3, randomized, double-blind, placebo-controlled, parallel-group trial included a 28-day pretreatment period and a 3-month treatment period. Patients with CM received subcutaneous fremanezumab quarterly (675 mg at baseline) or monthly (675 mg at baseline; 225 mg at Weeks 4 and 8), or placebo. Post hoc analyses evaluated the proportion of patients who reverted from CM to EM, defined as either a reduction to an average of <15 headache days per month during the 3-month treatment period or a reduction to <15 headache days per month in all 3 months of the treatment period.ResultsThis analysis included data from 1088 CM patients (quarterly, n = 366; monthly, n = 365; placebo, n = 357). More fremanezumab-treated patients with CM reverted to EM using either the monthly average number of headache days criteria for reversion (quarterly: 50.5% [185/366], P = .108; monthly: 53.7% [196/365], P = .012; vs placebo: 44.5% [159/357]) or the monthly headache day count at Months 1, 2, and 3 criteria for reversion (quarterly: 31.2% [114/366], P = .008; monthly: 33.7% [123/365], P = .001; vs placebo: 22.4% [80/357]). Patients with CM who reported previous topiramate or onabotulinumtoxinA use, concomitant preventive medication use, or medication overuse were less likely to revert to EM.ConclusionsFremanezumab may offer the benefit of reversion from CM to EM, based on a reduction in the number of headache days over 3 months of treatment.
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Project description:ObjectiveTo determine the effect of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody, in patients with chronic migraine and medication overuse.MethodsIn this double-blind, placebo-controlled study, 667 adults with chronic migraine were randomized (3:2:2) to placebo or erenumab (70 or 140 mg), stratified by region and medication overuse status. Data from patients with baseline medication overuse at baseline were used to assess changes in monthly migraine days, acute migraine-specific medication treatment days, and proportion of patients achieving ≥50% reduction from baseline in monthly migraine days.ResultsOf 667 patients randomized, 41% (n = 274) met medication overuse criteria. In the medication overuse subgroup, erenumab 70 or 140 mg groups had greater reductions than the placebo group at month 3 in monthly migraine days (mean [95% confidence interval] -6.6 [-8.0 to -5.3] and -6.6 [-8.0 to -5.3] vs -3.5 [-4.6 to -2.4]) and acute migraine-specific medication treatment days (-5.4 [-6.5 to -4.4] and -4.9 [-6.0 to -3.8] vs -2.1 [-3.0 to -1.2]). In the placebo and 70 and 140 mg groups, ≥50% reductions in monthly migraine days were achieved by 18%, 36% (odds ratio [95% confidence interval] 2.67 [1.36-5.22]) and 35% (odds ratio 2.51 [1.28-4.94]). These clinical responses paralleled improvements in patient-reported outcomes with a consistent benefit of erenumab across multiple measures of impact, disability, and health-related quality of life. The observed treatment effects were similar in the non-medication overuse subgroup.ConclusionsErenumab reduced migraine frequency and acute migraine-specific medication treatment days in patients with chronic migraine and medication overuse, improving disability and quality of life.Clinicaltrialsgov identifierNCT02066415.Classification of evidenceThis study provides Class II evidence that erenumab reduces monthly migraine days at 3 months in patients with chronic migraine and medication overuse.
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Project description:ObjectivesThe management of chronic migraine (CM) with Medication Overuse Headache (MOH) consists of withdrawal therapy, education on medications' use and prescription of prophylaxis. Little attention has been given to patients who fail in achieving a successful short-term outcome after withdrawal: we aim to describe predictors of failure.MethodsPatients with CM and MOH were enrolled at the Neurological Institute C. Besta of Milano, and included if they completed the three months follow-up. Withdrawal failure was defined as the situation in which patients either did not revert from chronic to episodic migraine (EM), were still overusing acute medications, or both did not revert to EM and kept overusing acute medications. Predictors of failure were addressed with a logistic regression, and for all variables, the longitudinal course in the two groups was described.ResultsIn 39, out of 137 patients, withdrawal was unsuccessful: the predictors included day-hospital-based withdrawal (OR: 2.37; 95% CI: 1.06-5.29), emergency room (ER) access before withdrawal (OR: 2.81; 95% CI: 1.13-6.94) and baseline headache frequency >69 days/three months (OR: 2.97; 95% CI: 1.32-6.65). Patients who failed withdrawal did not improve on medications intake, use of prophylactic and non-pharmacological treatments, symptoms of anxiety and depression.ConclusionsPatients who were treated in day-hospital, those who recently attended ER for headache, and those with more than 69 headache/3 months, as well as to those with relevant symptoms of anxiety and depression who did not improve should be closely monitored to reduce likelihood of non-improvement after structured withdrawal.
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Project description:Chronic migraine patients are at risk of developing a medication overuse. Brain functional studies in these patients have demonstrated an orbitofrontal hypometabolism, persistent after overuse cessation. Orbitofrontal dysfunction is also present in addiction and thus could predispose migraineurs to medication overuse. The aim of this study was to investigate if orbitofrontal dysfunction can be demonstrated in patients with chronic migraine and medication overuse by performing a systematic neuropsychological evaluation focused on tests that assess frontal lobe function. Second, to establish whether it is related to the outcome of these patients. We prospectively studied 42 chronic migraine patients with medication overuse, 42 episodic migraineurs and 41 controls on a battery of neuropsychological tasks evaluating the orbitofrontal and dorsolateral functioning. Depression, anxiety, and personality traits were also assessed. Chronic migraineurs with medication overuse showed a significant impairment in orbitofrontal task performance and higher depression scores as compared to episodic migraineurs and controls. Dorsolateral dysfunction was present in both groups of migraneurs, who also had higher rates of anxiety as compared to controls. After 1 year of follow-up, migraine patient's outcome was classified according to their medication overuse status. A negative outcome that included persistent or new-onset medication overuse was present in 34% of migraineurs and was associated with baseline poor orbitofrontal task performance, and with mild dorsolateral dysfunction, higher rates of depression, anxiety and neuroticism-anxiety traits. Formal education and years with migraine did not influence outcome. Orbitofrontal dysfunction is present in patients with chronic migraine and medication overuse, and associates with a poor outcome at 1 year of follow-up. Neuropsychological evaluation in migraine may help to detect patients prone to overuse so that appropriate therapeutic attitudes can be taken.
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Project description:The management of Medication overuse headache (MOH) represents a difficult challenge for clinicians and headache experts, particularly for the responder rate after a successful withdrawal treatment. The purpose of this study was to investigate the role of demographic and clinical characteristics as well as the score of Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Disability Questionnaire and Leeds Dependence Questionnaire in predicting a response after a successful withdrawal treatment in patients with MOH.This ancillary study is part of a randomized trial that demonstrated the safety and the efficacy of a 3-month treatment with sodium valproate (VPA) (800 mg/day vs placebo) in MOH. Demographic and clinical characteristics and questionnaire results were obtained from the entire sample.A significant correlation was found only between MOH relapse and the total MSQ score, the Role Preventive sub-scale and the Emotional Function sub-scale, suggesting a poorer quality of life in non responders.A high MSQ score could be associated with a poor short-term outcome in MOH patients after a successful treatment with detoxification followed by a new treatment.
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Project description:BackgroundIn daily practice, anti-CGRP monoclonal antibodies (MAbs) may be useful in chronic migraine (CM) with medication overuse (MO), but data is limited. We evaluated their effectiveness in a real-life clinical cohort.MethodsThis is a prospective study conducted in CM patients with and without medication overuse treated with monthly MAbs during 6 months (erenumab/galcanezumab). We collected headache characteristics, including acute medication intake, through an electronic diary. We compared patients (1) with and without MO at baseline, (2) with and without ongoing MO after treatment, defining MO resolution as < 10 or 15 days/month of acute medication intake, according to analgesic type, during the 6-month treatment.ResultsOf 139 CM patients completing 6-month treatment with anti-CGRP MAbs, 71.2% (99/139) had MO at baseline. After 6 months, patients with and without MO at baseline had significant and similar proportions of ≥50% reduction in migraine days/month (MO: 63.6% vs. non-MO: 57.5%, p = 0.500). 60.6% (60/99) no longer satisfied MO definition. Reduction in headache frequency compared to baseline occurred in both MO-ongoing and MO-resolution group, although those who stopped overusing had a greater improvement (headache days/month: - 13.4 ± 7.6 vs. -7.8 ± 7.2, p < 0.0001). No differences in MO resolution were observed according to the MAbs used. Baseline lower pain severity was associated with MO resolution (OR [95%]:0.236[0.054-0.975]; p = 0.049).ConclusionsIn real-life anti-CGRP MAbs are as effective in CM patients with MO as in patients without it and facilitate MO cessation. Reduction in headache frequency and acute medication days/month occurs regardless of whether patients stop overusing or not.
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