OnabotulinumtoxinA: A Review in the Prevention of Chronic Migraine.
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ABSTRACT:
SUBMITTER: Frampton JE
PROVIDER: S-EPMC5915521 | biostudies-other | 2018 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundMonoclonal antibodies (mAbs) targeting the CGRP pathway are safe and efficacious therapies for the prevention of migraine. In this study we assessed the effects of discontinuation of preventive erenumab and galcanezumab treatment in patients with chronic migraine.MethodsThis retrospective pooled analysis included completers of the open-label extension study phase for the preventive treatment of chronic migraine with galcanezumab (NCT02614261; 9 months) and erenumab (NCT02174861; 12 months) in a single headache center. We compare migraine data until week 12 after open-label treatment completion, when patients did not have any pharmacological preventive medication, to study baseline values of the double-blind trial period, and to the last 4 weeks of the open-label extension. The assessment included changes in monthly migraine days, headache hours, days with severe headache and acute headache medication use.ResultsData from 16 patients after galcanezumab (n = 9) and erenumab (n = 7) open-label treatment completion were analyzed. The mean number of monthly migraine days was 18.38 ± 3.74 at baseline, and 12.19 ± 4.53 in the last 4 weeks of the open-label extension (p < 0.001). Monthly migraine days remained significantly reduced compared to baseline during the entire 12-week observation period after open-label termination (p = 0.002), with a reduction of 5.38 ± 4.92 in weeks 1-4 (p = 0.001), 4.75 ± 4.15 in weeks 5-8 (p = 0.001), and 3.93 ± 5.45 in weeks 9-12 (p = 0.014). There was no significant difference in monthly migraine days between the 12 weeks after open-label termination and the last 4 weeks of the open-label phase (p = 0.228). All other analyses revealed numerical improvement through week 12 in comparison to baseline.ConclusionsIn this small, self-selected cohort, the results indicate a therapeutic effect of monoclonal antibodies targeting the CRGP pathway in chronic migraine prevention after treatment termination up to 12 weeks.
| S-EPMC6734267 | biostudies-literature
Project description:BackgroundChronic migraine is a highly debilitating condition that is often difficult to manage, particularly in the presence of medication overuse headache. Drugs targeting the calcitonin gene-related peptide (CGRP), or its receptor have shown promising results in treating this disorder.MethodsWe searched Pubmed and Embase to identify randomized clinical trials and real-world studies reporting on the use of medication targeting the calcitonin gene-related peptide in patients with chronic migraine.ResultsA total of 270 records were identified. Nineteen studies qualified for the qualitative analysis. Most studies reported on monoclonal antibodies targeting CGRP (anti-CGRP mAbs), that overall prove to be effective in decreasing monthly migraine days by half in about 27.6-61.4% of the patients. Conversion from chronic to episodic migraine was seen in 40.88% of the cases, and 29-88% of the patients stopped medication overuse. Obesity seems to be the main negative predictor of response to anti-CGRP mAbs. There is no evidence to suggest the superiority of one anti-CGRP mAb. Despite the lack of strong evidence, the combination of anti-CGRP medication with onabotulinumtoxinA in chronic migraine is likely to bring benefits for resistant cases. Atogepant is the first gepant to demonstrate a significant decrease in monthly migraine days compared to placebo in a recent trial. Further, anti-CGRP mAb and gepants have a good safety profile.ConclusionThere is strong evidence from randomized trials and real-world data to suggest that drugs targeting CGRP are a safe and effective treatment for chronic migraine.
| S-EPMC10996229 | biostudies-literature
Project description:ObjectiveTo evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks.MethodsIn this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use.ResultsFifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were -1.4 (nVNS) and -0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was -7.9 (95% confidence interval -11.9 to -3.8; p < 0.01).ConclusionsTherapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed.Clinicaltrialsgov identifierNCT01667250.Classification of evidenceThis study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS.
| S-EPMC4970666 | biostudies-literature
Project description:Aims:Migraine is a global phenomenon, affecting more than 10% of the world's population. It is characterized by unilateral headache that may be accompanied by vomiting, nausea, photophobia and phonophobia. Some patients with chronic migraine respond to extra-cranial botulinum toxin type A injection, although the benefits observed are temporary. The rationale for surgical trigger site deactivation is to achieve lasting symptomatic improvement or permanent relief from migraine. Methods:We performed a PRISMA-compliant systematic review of clinical studies evaluating surgical intervention for migraine by searching Ovid MEDLINE and EMBASE databases from inception to June 2017. Studies were independently screened by two authors. Data were extracted on study characteristics, migraine outcomes, adverse events and recurrence. The quality of evidence was assessed using the GRADE approach. The review protocol was prospectively registered on the PROSPERO database (CRD42017068577). Results:The search strategy identified 789 articles; of them, 18 studies (4 RCTs and 14 case series) were eligible for analysis. Surgical interventions were heterogeneous and variably involved peripheral nerve decompression by myectomy or foraminotomy, nerve excision, artery resection and/or nasal surgery. All studies reported significant reductions in migraine intensity, frequency, duration and composite headache scores following surgery. Study heterogeneity precluded formal meta-analysis. Where reported, adverse event rates varied markedly between studies. The quality of included studies was consistently low or very low. Conclusion:There is insufficient evidence to support the effectiveness of any specific surgical intervention for chronic migraine, especially with regard to permanent relief; however, all included studies report improvements in key outcomes following migraine surgery. A definitive, well-powered RCT with objective surgical and patient-reported outcome measures and robust adverse event reporting is required.
| S-EPMC7061614 | biostudies-literature
Project description:BACKGROUND:Health economic models are critical tools to inform reimbursement agencies on health care interventions. Many clinical trials report outcomes using the frequency of an event over a set period of time, for example, the primary efficacy outcome in most clinical trials of migraine prevention is mean change in the frequency of migraine days (MDs) per 28?days (monthly MDs [MMD]) relative to baseline for active treatment versus placebo. Using these cohort-level endpoints in economic models, accounting for variation among patients is challenging. In this analysis, parametric models of change in MMD for migraine preventives were assessed using data from erenumab clinical studies. METHODS:MMD observations from the double-blind phases of two studies of erenumab were used: one in episodic migraine (EM) (NCT02456740) and one in chronic migraine (CM) (NCT02066415). For each trial, two longitudinal regression models were fitted: negative binomial and beta binomial. For a thorough comparison we also present the fitting from the standard multilevel Poisson and the zero inflated negative binomial. RESULTS:Using the erenumab study data, both the negative binomial and beta-binomial models provided unbiased estimates relative to observed trial data with well-fitting distribution at various time points. CONCLUSIONS:This proposed methodology, which has not been previously applied in migraine, has shown that these models may be suitable for estimating MMD frequency. Modelling MMD using negative binomial and beta-binomial distributions can be advantageous because these models can capture intra- and inter-patient variability so that trial observations can be modelled parametrically for the purposes of economic evaluation of migraine prevention. Such models have implications for use in a wide range of disease areas when assessing repeated measured utility values.
| S-EPMC6343253 | biostudies-literature
Project description:OBJECTIVE:As a post-approval commitment, this dose-ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents. BACKGROUND:In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010. METHODS:This multicenter, double-blind, parallel-group, randomized trial assessed a single treatment of onabotulinumtoxinA (155 U or 74 U) vs placebo (intramuscular saline) administered via the recommended fixed-dose fixed site paradigm in adolescents with CM aged 12 to <18 years. The primary efficacy measure was change in frequency of headache days from baseline at week 12; other measures included change in frequency of headache days at weeks 4 and 8 and change in frequency of severe headache days. Safety and tolerability were assessed. RESULTS:Of 125 randomized patients (onabotulinumtoxinA 155 U, n = 45; onabotulinumtoxinA 74 U, n = 43; placebo, n = 37), all were included in the primary efficacy analysis, and 115 (92.0%) completed the study. Lack of efficacy was the primary reason for discontinuing (n = 4; 3.2%); no patients discontinued because of adverse events. All treatments reduced frequency of headache days at week 12, with no significant differences between treatments. The mean (95% confidence interval) changes from baseline in the frequency of headache days during the 28-day period ending at week 12 (primary endpoint) were -6.3 (-8.5, -4.2), -6.4 (-8.8, -4.0), and -6.8 (-9.6, -4.1) days in the onabotulinumtoxinA 155 U, onabotulinumtoxinA 74 U, and placebo groups, respectively (P ? .474). All treatments reduced frequency of severe headache days and were well-tolerated; serious adverse events (n = 3) were considered unrelated to treatment and resolved without sequelae. The most commonly reported treatment-emergent adverse events were neck pain (n = 8), upper respiratory tract infection (n = 7), migraine, and nasopharyngitis (n = 5 each). CONCLUSION:Although this study did not meet its efficacy endpoints, onabotulinumtoxinA was well tolerated in this adolescent population. Given previous data demonstrating the benefits of onabotulinumtoxinA in adults with CM, additional studies with design modifications, including adequate statistical power, to assess the efficacy of multiple treatment cycles of onabotulinumtoxinA for CM prevention in adolescents may be informative.
| S-EPMC7065250 | biostudies-literature
Project description:ObjectivesTo assess the effects of botulinum toxin for prevention of migraine in adults.DesignSystematic review and meta-analysis.Data sourcesCENTRAL, MEDLINE, Embase and trial registries.Eligibility criteriaWe included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache.Data extraction and synthesisCochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed.ResultsTwenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of -2.0 migraine days/month (95% CI -2.8 to -1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of -2.70 cm (95% CI -3.31 to -2.09, n=75) and -4.9 cm (95% CI -6.56 to -3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes.ConclusionsIn chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.
| S-EPMC6661560 | biostudies-literature
Project description:BackgroundChronic migraine is a debilitating headache disorder that has significant impact on quality of life. Stimulation of peripheral nerves is increasingly being used to treat chronic refractory pain including headache disorders. This systematic review examines the effectiveness and adverse effects of occipital nerve stimulation (ONS) for chronic migraine.MethodsDatabases, including the Cochrane Library, MEDLINE, EMBASE, CINAHL and clinical trial registers were searched to September 2014. Randomized controlled trials (RCTs), other controlled and uncontrolled observational studies and case series (n? 10) were eligible. RCTs were assessed using the Cochrane risk of bias tool. Meta-analysis was carried out using a random-effects model. Findings are presented in summary tables and forest plots.ResultsFive RCTs (total n=402) and seven case series (total n=115) met the inclusion criteria. Pooled results from three multicenter RCTs show that ONS was associated with a mean reduction of 2.59 days (95% CI 0.91 to 4.27, I2=0%) of prolonged, moderate to severe headache per month at 3 months compared with a sham control. Results for other outcomes generally favour ONS over sham controls but quantitative analysis was hampered by incomplete publication and reporting of trial data. Lead migration and infections are common and often require revision surgery. Open-label follow-up of RCTs and case series suggest long-term effectiveness can be maintained in some patients but evidence is limited.ConclusionsWhile the effectiveness of ONS compared to sham control has been shown in multiple RCTs, the average effect size is modest and may be exaggerated by bias as achieving effective blinding remains a methodological challenge. Further measures to reduce the risk of adverse events and revision surgery are needed.Systematic review registrationthis systematic review is an update and expanded work of part of a broader review registered with PROSPERO. Registration No. CRD42012002633.
| S-EPMC4368787 | biostudies-literature
Project description:OBJECTIVE:To compare the methods and baseline characteristics of the American Migraine Prevalence and Prevention (AMPP) and Chronic Migraine Epidemiology and Outcomes (CaMEO) studies. BACKGROUND:The AMPP and CaMEO studies are the largest longitudinal efforts designed to improve our understanding of episodic and chronic migraine in the United States. The studies have complementary strengths and weaknesses. METHODS:This analysis compares and contrasts the study methods and participation rates of the AMPP and CaMEO studies. We then compare and contrast baseline results in terms of demographic characteristics, headache features, and disability as measured by the Migraine Disability Assessment Scale (MIDAS) among people with episodic and chronic migraine. RESULTS:AMPP and CaMEO sampled from panels constructed to be representative of the US population. The AMPP Study collected data using a mailed questionnaire while CaMEO relied on a web survey methodology. Response rates were higher in AMPP (64.8%) than in CaMEO (16.5%). Both studies assessed headache features using the American Migraine Study/AMPP diagnostic module. Both identified persons with episodic (<15 headache days/month) and chronic migraine (?15 headache days/month) based on the International Classification of Headache Disorders. AMPP collected data annually over 5 years, while CaMEO collected data quarterly over 15 months. Baseline demographic distribution was generally similar, indicating that each study was broadly representative of the US population. The proportion of persons with migraine who had chronic migraine was similar (AMPP, 6.6%; CaMEO, 8.8%). Respondents had similar median headache frequency (days/month) by sex for chronic migraine (AMPP: men?=?21.7, women?=?20.0; CaMEO: men?=?20.0, women?=?20.0) and episodic migraine (AMPP: men?=?1.7, women?=?2.0; CaMEO: men?=?2.0, women?=?3.0). Median MIDAS scores were substantially higher in both studies for chronic migraine (severe disability [Grade IV]; AMPP: men?=?33.0, women?=?45.0; CaMEO: men?=?32.0, women?=?38.0) than episodic migraine (little/mild disability [Grade I/II]; AMPP: men?=?3.0, women?=?6.0; CaMEO: men?=?4.0, women?=?7.0). Rates of moderate/severe disability (Grade III/IV) were substantially higher in both studies for chronic migraine (AMPP: men?=?66.9%, women?=?78.9%; CaMEO: men?=?71.0%, women?=?82.6%) than episodic migraine (AMPP: men?=?23.0%, women?=?31.8%; CaMEO: men?=?26.7%, women?=?37.9%). More women than men respondents in both studies experienced moderate/severe disability. CONCLUSIONS:AMPP and CaMEO are longitudinal cohort studies that used different methods, but yielded similar results for demographic features, headache frequency, and headache-related disability. Both studies found more severe headache-related disability in those with chronic versus episodic migraine.
| S-EPMC5132024 | biostudies-literature
Project description:BACKGROUND:PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24?weeks of treatment. METHODS:Patients received up to two 30-min IV administrations of eptinezumab 100?mg, 300?mg, or placebo separated by 12?weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). RESULTS:A total of 1072 adults received treatment: eptinezumab 100?mg, n?=?356; eptinezumab 300?mg, n?=?350; placebo, n?=?366. The reduction in mean monthly migraine days observed during the first dosing interval (100?mg, -?7.7?days; 300?mg, -?8.2?days; placebo, -?5.6?days) was further decreased after an additional dose (100?mg, -?8.2?days; 300?mg, -?8.8?days; placebo, -?6.2?days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ?50% and???75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (?50% MRRs weeks 13-24: 100?mg, 61.0%; 300?mg, 64.0%; placebo, 44.0%; and???75% MRRs weeks 13-24: 100?mg, 39.3%; 300?mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. CONCLUSION:Eptinezumab 100?mg or 300?mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24?weeks and demonstrated an acceptable safety profile in patients with chronic migraine. TRIAL REGISTRATION:ClinicalTrials.gov (Identifier: NCT02974153 ). Registered November 23, 2016.
| S-EPMC7539382 | biostudies-literature