OnabotulinumtoxinA in Chronic Migraine: A Profile of Its Use.
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SUBMITTER: Frampton JE
PROVIDER: S-EPMC7772159 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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OnabotulinumtoxinA in Chronic Migraine: A Profile of Its Use.
CNS drugs 20201211 12
OnabotulinumtoxinA (Botox<sup>®</sup>; a formulation of botulinum toxin type A (BoNT/A)] is indicated for the prevention of headaches in adults with chronic migraine (CM) in numerous countries, including those of Europe. In clinical trials, intramuscular administration of BoNT/A (155-195 units at 12-week intervals) to patients with CM was generally well tolerated and associated with sustained and clinically meaningful improvements in multiple assessments of headache symptoms, headache-related im ...[more]
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Project description:An intramuscular formulation of onabotulinumtoxinA (onabotA; Botox®) is currently the only therapy specifically approved for the prevention of headaches in adults with chronic migraine (CM) in the EU and North America. This article provides a narrative review of relevant data on the drug in this indication from an EU perspective. OnabotA was originally approved on the basis of pooled data from two phase III studies (PREEMPT 1 and 2). In these pivotal studies, injection of up to five cycles of onabotA (155-195 U/cycle) at 12-week intervals was generally well tolerated and effective in producing statistically significant and clinically meaningful improvements in headache symptoms, acute headache pain medication usage, headache impact and health-related quality of life in adults with CM, of whom approximately two-thirds were acute medication overusers and approximately one-third had failed to respond to???3 prior oral prophylactic therapies. More recently, the efficacy and tolerability of onabotA over a period of 1 year in the PREEMPT programme has been substantiated and extended by the results of a long-term phase IV study (COMPEL), in which patients received up to nine treatment cycles over a period of 2 years, and by findings from several real-world clinical practice studies from Europe, including the prospective multinational REPOSE and CM-PASS studies. In conclusion, the totality of evidence from clinical trials and real-world studies indicates that onabotA is an effective and generally well tolerated option for the prevention of CM that may be particularly useful for patients who have previously failed to respond to or are intolerant of commonly prescribed oral prophylactics.
| S-EPMC5915521 | biostudies-other
Project description:BackgroundChronic migraine (CM) is associated with substantial economic burden. Real-world data suggests that onabotulinumtoxinA treatment for CM reduces healthcare resource utilisation (HRU) and related costs.MethodsREPOSE was a 2-year prospective, multicentre, non-interventional, observational study to describe the real-world use of onabotulinumtoxinA in adult patients with CM. This analysis examined the impact of onabotulinumtoxinA on HRU. Patients received onabotulinumtoxinA treatment approximately every 12 weeks according to their physicians' discretion, guided by the summary of product characteristics (SPC) and PREEMPT injection paradigm. HRU outcome measures were collected at baseline and all administration visits and included headache-related hospitalizations and healthcare professional (HCP) visits. Health economic data, including family doctor and specialist visits, inpatient treatment for headache, acupuncture, technical diagnostics, use of nonpharmacologic remedies, and work productivity were also collected for patients enrolled at German study centres.ResultsOverall, 641 patients were enrolled at 78 study centres across 7 countries (Germany, UK, Italy, Spain, Norway, Sweden, and Russia), 633 received ≥1 onabotulinumtoxinA dose, and 128 completed the 2-year study. Patients were, on average, aged 45 years, 85% were female, and 60% (n = 377) were from Germany. At the end of the 2-year observation period, significantly fewer patients reported headache-related hospitalizations (p < 0.02) and HCP visits (p < 0.001) within the past 3 months than in the 3 months before baseline. In the German population, reductions were observed across all health services at all follow-up visits compared with baseline. The percentage of patients who saw a family doctor decreased from 41.7% at baseline to 13.5% at administration visit 8 and visits to a medical specialist decreased from 61.7% to 5.2% of patients. Inpatient acute treatment and technical diagnostics declined from 6.4% and 19.7% of patients at baseline to 0.0% and 1.0% at administration 8, respectively. The use of nonpharmacologic remedies and medication for the acute treatment of migraine also decreased with continued onabotulinumtoxinA treatment. Work incapacity, disability, absenteeism, and impaired performance at school/work improved with onabotulinumtoxinA treatment for CM over the 2-year observation period.ConclusionsReal-world evidence from REPOSE demonstrates that onabotulinumtoxinA treatment is associated with decreased HRU and supports the long-term benefits associated with the use of onabotulinumtoxinA for CM in clinical practice.Trial registrationNCT01686581 . Name of registry: ClinicalTrials.gov. URL of registry: Date of retrospective registration: September 18, 2012. Date of enrolment of first patient: July 23, 2012.
| S-EPMC8173963 | biostudies-literature
Project description:BackgroundAnatomical and experimental data indicate that onabotulinimtoxin A could be more efficient and cost-effective for treating chronic migraine with injections targeting the cranial sutures, where collaterals from the meninges penetrate the skull.MethodsA new injection paradigm (FollowTheSutures) was tested for safety, tolerability and feasibility in a Phase II, open-label, non-controlled, single-center pilot study. Ninety units of onabotulinimtoxin A (Botox®), were injected in 18 sites over the area of the cranial sutures. Adverse events and potential beneficial effects were recorded in a headache diary at least 4 weeks before, and for 12 weeks after the injections. A higher dilution than normal of onabotulinimtoxin A was used to get better diffusion.ResultsNineteen (of 20 included) women with chronic migraine received the injections and were evaluable. There was only one treatment-related adverse event (reduced power of chewing for some weeks). Otherwise, the procedure was overall well tolerated. Patients improved on most efficacy parameters after the injections. There was little or no effect on glabellar or forehead lines.ConclusionsThe protocol was safe and well tolerated. Lower risk of unblinding due to the absence of cosmetic effects should make the injection procedure well suited for a large, randomized, placebo-controlled study. If efficacy is confirmed, it will be markedly less costly than the standard procedure.Trial registration: EUDRACT (2017-002516-13), ClinicalTrials.gov (NCT03543254).
| S-EPMC9109235 | biostudies-literature
Project description: Not available
| S-EPMC9300070 | biostudies-literature
Project description:BackgroundThe PREEMPT Studies established onabotulinumtoxinA as preventive treatment for adults with chronic migraine (CM). The purpose of the REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilisation, and Patient-reported OutcomeS observed in practice (REPOSE) Study was to observe real-life, long-term (24-month) use of onabotulinumtoxinA in adults with CM and report on the utilisation, effectiveness, safety, and tolerability.MethodsThe REPOSE Study was a European, open-label, multicentre, prospective, noninterventional study. Patients received onabotulinumtoxinA approximately every 12 weeks according to their physician's usual practice, guided by the summary of product characteristics (SPC). Patients were observed for 24 months after initiating onabotulinumtoxinA treatment. Outcome measures were collected at baseline and all administration visits and included onabotulinumtoxinA injection practices, headache-day frequency, Migraine-Specific Quality-of-Life Questionnaire (MSQ), EuroQol 5-Dimension Questionnaire (EQ-5D), and adverse drug reactions (ADRs) to evaluate safety/tolerability.ResultsOf 641 patients enrolled, 633 received ≥1 dose of onabotulinumtoxinA for a total of 3499 treatment sessions. At baseline, mean (SD) age was 45.4 (11.7) years; patients were predominantly women (85.3%). Injection practices closely followed the SPC in mean dosage (155.1 U) and injection sites per session (31.4), with the exception of a prolongation of the recommended 12-week dosing interval, with 79.1% of patients receiving ≥1 treatment session that was > 13 weeks after the previous treatment session. Headache-day frequency was reduced from a baseline mean (SD) of 20.6 (5.4) to 7.4 (6.6) days at administration visit 8 (P < 0.001). Each MSQ domain (restrictive, preventive, and emotional) was significantly reduced from baseline through each administration visit (P < 0.001). The median EQ-5D total and health state scores were significantly improved from baseline through each administration visit (P < 0.001). Overall, 18.3% of patients reported an ADR; most were mild to moderate intensity, with only 1.3% of patients reporting a serious ADR. Eyelid ptosis (5.4%), neck pain (2.8%), and musculoskeletal stiffness (2.7%) were the most frequently reported.ConclusionsLong-term, real-world preventive treatment of CM with onabotulinumtoxinA showed effectiveness with a sustained reduction in headache-day frequency and significant improvement in quality-of-life measures. ADRs were mild to moderate, with no new safety concerns identified.Trial registrationTrial registration number: NCT01686581. Name of registry: ClinicalTrials.gov. URL of registry: https://clinicaltrials.gov/ct2/show/NCT01686581 . Date of retrospective registration: September 18, 2012. Date of enrolment of first patient: July 23, 2012.
| S-EPMC6734221 | biostudies-literature
Project description:BackgroundThe CGRP antagonists offer a novel therapeutic approach in migraine. Their utility in patients with severe forms of chronic migraine is a subject of particular interest. We present outcomes of 9 months of erenumab treatment in a cohort of patients with difficult-to-control chronic migraine, all of whom had prior unsatisfactory response to onabotulinumtoxinA.MethodsWe offered erenumab to 98 patients with a prior unsatisfactory response to onabotulinumtoxinA. Eighty of 98 had trialled greater occipital nerve injections (82%), 32/98 peripheral neurostimulation (33%) and 18/98 intravenous dihydroergotamine (18%). Thirty eight of 98 (39%) met the definition of triptan overuse and 43/98 (44%) analgesic overuse. All patients met the EHF criteria for 'resistant migraine'. Outcome measures (recorded monthly) included days with headache limiting activities of daily living ("red"), not limiting ("amber"), headache free ("green"), and requiring triptans or other analgesics. Quality of life scores - headache impact test 6 (HIT-6), patient health questionnaire 9 (PHQ-9) and pain disability index (PDI) - were also measured.ResultsMean number of red days improved by - 6.4 days (SE 0.67, 95%CI - 7.7 to - 5.1, p=0.001) at 3 months; - 6.8 days (SE 0.96, 95%CI - 8.80 to - 4.9, p=0.001) at 6 months and - 6.5 days (SE 0.86, 95%CI - 8.3 to - 4.8, p=0.001) at 9 months. Repeated measures ANOVA confirmed improvements in the number of red (p=0.001), green (p=0.001), triptan (p=0.001) and painkiller days (p=0.001) as well as scores of the HIT-6 (p=0.001), PHQ-9 (p=0.001), and PDI (p=0.001) across the duration of study.ConclusionWe observed improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment.
| S-EPMC7797151 | biostudies-literature
Project description:ObjectiveThe approved use of onabotulinumtoxinA for prophylaxis of headaches in patients with chronic migraine (CM) involves treatment every 12 weeks. It is currently unknown whether patients who fail to respond to the first onabotulinumtoxinA treatment cycle will respond to subsequent treatment cycles. To help inform decisions about treating non-responders, we examined the probability of treatment cycle 1 non-responders responding in cycle 2, and cycle 1 and 2 non-responders responding in cycle 3.MethodsPooled PREEMPT data (two studies: a 24-week, 2-cycle, double-blind, randomised (1:1), placebo-controlled, parallel-group phase, followed by a 32-week, 3-cycle, open-label phase) evaluated onabotulinumtoxinA (155-195 U) for prophylaxis of headaches in persons with CM (≥15 days/month with headache ≥4 h/day). End points of interest included the proportion of study patients who first achieved a ≥50% reduction in headache days, moderate/severe headache days, total cumulative hours of headache on headache days, or a ≥5-point improvement in Headache Impact Test (HIT)-6. For treatment cycle 1, all eligible participants were included. For subsequent cycles, responders in a previous cycle were no longer considered first responders.ResultsAmong onabotulinumtoxinA-treated patients (n=688) 49.3% had a ≥50% reduction in headache-day frequency during treatment cycle 1, with 11.3% and 10.3% of patients first responding during cycles 2 and 3, respectively. 54.2%, 11.6% and 7.4% of patients first responded with a ≥50% reduction in cumulative hours of headache, and 56.3%, 14.5% and 7.7% of patients first responded with a ≥5-point improvement in total HIT-6 during treatment cycles 1, 2 and 3, respectively.ConclusionsA meaningful proportion of patients with CM treated with onabotulinumtoxinA who did not respond to the first treatment cycle responded in the second and third cycles of treatment.Trial registration numberNCT00156910, NCT00168428.
| S-EPMC4552933 | biostudies-literature
Project description:Objective The main objective of this pilot study was to investigate the safety of administering onabotulinumtoxinA towards the sphenopalatine ganglion in 10 patients with intractable chronic migraine with an open, uncontrolled design. We also collected efficacy data to provide an indication as to whether future placebo-controlled studies should be performed. Method In a prospective, open-label, uncontrolled study after one-month baseline, we performed bilateral injections of 25 IU onabotulinumtoxinA (total dose 50 IU) toward the sphenopalatine ganglion in a single outpatient session in 10 patients with intractable migraine with a follow-up of 12 weeks. The primary outcome was adverse events and the main efficacy outcome was frequency of moderate and severe headache days in month 2 post-treatment compared to baseline. Results All 10 patients experienced a total of 25 adverse events. The majority of these were different types of local discomfort in the face and jaw, and none were classified as serious. In an intention-to-treat analysis of the main efficacy outcome, a statistically significant reduction of moderate and severe headache days in baseline versus month 2 was observed (16.3 ± 6.2 days baseline versus 7.6 ± 7.6 days month 2, p = 0.009). Eight out of 10 patients experienced an at least 50% reduction of moderate and severe headache days compared to baseline. Conclusion The result warrants randomised, placebo-controlled studies to establish both safety and efficacy of this potential novel treatment of chronic migraine.
| S-EPMC5394468 | biostudies-literature
Project description:Background and purposeOnabotulinumtoxinA was effective and well tolerated for prophylaxis of headache in patients with chronic migraine (CM) in two randomized, double-blind, placebo-controlled, phase 3 trials. To further assess the safety and tolerability of onabotulinumtoxinA in CM prophylaxis in adults, the pooled safety data from four double-blind, placebo-controlled trials were analyzed.MethodsThe pooled analysis included two phase 2 and two phase 3 double-blind, placebo-controlled trials. The safety population was 2436 patients, 1997 of whom received ≥1 dose of onabotulinumtoxinA. The studies shared similar dosing intervals (approximately 12 weeks) with doses between 75 and 260 U. Safety assessments included adverse events (AEs), physical examination and clinical laboratory tests.ResultsOnabotulinumtoxinA was safe and well tolerated, with a low discontinuation rate (3.4%) due to AEs. The majority of patients in this pooled analysis received doses between 150 and 200 U, with an average of 163 U per treatment cycle. Of the 1997 patients who received any onabotulinumtoxinA injections, 1455 patients (72.9%) reported at least one AE. Neck pain (12.6%) was the most common onabotulinumtoxinA-associated AE, followed by muscle weakness (8.0%), musculoskeletal stiffness (6.1%) and eyelid ptosis (4.6%). Serious AEs were infrequent, occurring in 5.4% of patients who received any onabotulinumtoxinA treatment and 3.0% of patients receiving placebo. AEs were consistent with the known tolerability profile of onabotulinumtoxinA.ConclusionsMultiple treatments with onabotulinumtoxinA at doses of 75-260 U administered every 12 weeks, and up to five treatment cycles, were well tolerated for the prophylaxis of headache in adults with CM.
| S-EPMC4233954 | biostudies-literature
Project description:ObjectiveAs a post-approval commitment, this dose-ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents.BackgroundIn 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.MethodsThis 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.ResultsOf 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).ConclusionAlthough 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