OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program.
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SUBMITTER: Lipton RB
PROVIDER: S-EPMC4959035 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
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OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program.
Lipton Richard B RB Rosen Noah L NL Ailani Jessica J DeGryse Ronald E RE Gillard Patrick J PJ Varon Sepideh F SF
Cephalalgia : an international journal of headache 20160610 9
<h4>Background</h4>Chronic migraine (CM) is associated with high impact and reduced health-related quality of life (HRQoL).<h4>Methods</h4>Patients with CM from PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) were randomized (1:1) to receive onabotulinumtoxinA or placebo for two 12-week cycles in the double-blind (DB) phase, followed by three 12-week cycles of open-label (OL) onabotulinumtoxinA (onabotulinumtoxinA/onabotulinumtoxinA (O/O) and placebo/onabotulinumtoxinA (P/O) g ...[more]
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Project description:IntroductionThe double-blind, phase 3 PREEMPT trials demonstrated the efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. This post hoc analysis evaluated the effect of onabotulinumtoxinA on clinically meaningful changes in headache severity, headache-related impact, and quality of life.MethodsPooled, 24-week data were used to determine percentages of patients meeting responder criteria for the change in headache days (≥ 50% reduction in headache-day frequency), Headache Impact Test (HIT-6; ≥ 5-point improvement), MSQ Role Function-Restrictive (MSQ-RFR; ≥ 10.9-point improvement), and Average Daily Headache Severity (ADHS; ≥ 1-point improvement on a 4-point ordinal scale [0 = no pain, 3 = severe pain]).ResultsIn the pooled analysis population (N = 1384; onabotulinumtoxinA, n = 688; placebo, n = 696), significantly more patients treated with onabotulinumtoxinA compared with placebo were responders on HIT-6 (40.8 vs. 25.3%), MSQ-RFR (59.0 vs. 40.2%), and ADHS (35.5 vs. 22.4%) measures, and achieved traditional ≥ 50% reduction in headache days (44.8 vs. 34.2%; all P < 0.001). At least one responder criterion was met by 72.1% and 56.6% of onabotulinumtoxinA- and placebo-treated patients, respectively; all four were met by 20.4% and 8.6%, respectively (P < 0.001). Linear regression analysis showed that approximately 20% of the variance in HIT-6 and MSQ-RFR improvement was explained by improvement in headache days.ConclusionsTreatment with onabotulinumtoxinA for 24 weeks was associated with clinically meaningful benefits beyond reduction in headache days; including reductions in headache severity and headache-related impact, and improved quality of life. While 45% of patients met responder criteria for monthly headache days, over 70% had clinically meaningful improvements on at least one outcome measure.Trial registrationClinicalTrials.gov identifier, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2).
| S-EPMC7648806 | biostudies-literature
Project description:OnabotulinumtoxinA has been shown to reduce headache-days among patients with chronic migraine (CM). The objective of this analysis was to determine whether onabotulinumtoxinA has an impact on headache-day severity in patients with CM among those patients who were deemed non-responders based on reduction in the frequency of headache days alone.Data from the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trial program (a 24-week, 2-treatment cycle, double-blind, randomized, placebo-controlled, parallel-group phase, followed by a 32-week, 3-treatment cycle, open-label phase) were pooled for analysis. Patients kept a daily diary to record headache severity on a 4-point scale (from none to severe), and a 6-domain Headache Impact Test (HIT-6) was used to determine the clinical impact of headaches. Analysis was undertaken to assess whether the subset of patients that were headache-day frequency non-responders at week 24 (patients with <50% reduction in headache-day frequency) experienced a reduction in headache severity whilst receiving onabotulinumtoxinA.For headache-day frequency non-responders, significant reductions in the number of severe headache days, average daily headache severity, pooled percentage of severe headache days and headache severity score were observed at week 24 for patients who had received onabotulinumtoxinA compared with those who had received placebo. The between-group differences were reduced and non-significant at week 56. Similarly, headache-day frequency non-responders receiving onabotulinumtoxinA were found to have an improvement in the clinical impact of headaches using results from the HIT-6.These results suggest that even those patients with CM who are deemed non-responders based on analysis of headache frequency alone experience clinically meaningful relief from headache intensity following treatment with onabotulinumtoxinA.
| S-EPMC5539058 | biostudies-literature
Project description:The 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.Pooled 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.Among 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.A 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.NCT00156910, NCT00168428.
| S-EPMC4552933 | biostudies-literature
Project description:ObjectiveChronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study.Materials and methodsPREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported.ResultsOf 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials.ConclusionsThis subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.
| S-EPMC4033567 | 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: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:OnabotulinumtoxinA (Botox®; 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 impact and/or disability and migraine-specific health-related quality of life over a period of 1 year (in the pivotal PREEMPT 1 and 2 studies) and 2 years (in the phase IV COMPEL study). The efficacy and safety of BoNT/A therapy have been confirmed in a number of large, prospective, real-world studies conducted in Europe, including the 2-year REPOSE study. Intramuscular BoNT/A has also demonstrated greater clinical utility than the oral prophylactic medication topiramate in a clinical practice setting (FORWARD study).
| S-EPMC7772159 | biostudies-literature
Project description:Background: Existing data suggest that after returning to sports post-concussion, athletes are at an increased risk of sustaining a subsequent injury. Exploring methods that may reduce injury risk following successful post-concussion return-to-play may lead to new treatment approaches. Hypothesis/Purpose: Our purpose was to examine the efficacy of a neuromuscular training (NMT) intervention on acute, time-loss sport-related injury over the subsequent year relative to standard-of-care among adolescent athletes, using a prospective randomized clinical trial design. We hypothesized the hazard of injury over the year after concussion RTP would be greater for those randomized to standard-of-care relative to those randomized to the NMT intervention. Methods: Twenty-seven youth athletes were assessed initially post-concussion (median=7; interquartile range [IQR]=5-10 days post-concussion) and following return-to-play clearance (median=40, IQR=15-52 days post-concussion). After return-to-play clearance, they were randomly assigned to NMT intervention (n=11, mean=14.7±1.7 years; 36% female; Table 1) or standard-of-care (n=16, mean=15.3±1.8 years; 44% female; Table 1) groups. The intervention (duration=8 weeks; frequency=2x/week) included guided strength, landing, and stability exercises with landing stabilization focus. Standard-of-care received no recommendations. Randomization strata included age and sex. For the subsequent year, athletes prospectively completed a monthly log documenting sport-related injuries and the number/hours of organized sport competitions. Clinical Trial Registration Number: NCT03917290. Results: During the first year after post-concussion return-to-play clearance, time-loss sport-related injuries were more common among standard-of-care relative to neuromuscular training intervention (75% vs. 36%). After adjusting for the randomization strata (age and sex), the hazard of subsequent injury in the standard-of-care group was 3.56 [95% CI=1.11, 11.49, p=0.0334] times the hazard of subsequent injury in the neuromuscular training intervention group. Sport participation was similar between neuromuscular training intervention and standard-of-care groups during the year-long monitoring period (median=12 [IQR=2.6, 32.1] vs. 15.6 [IQR=3.5, 105.9] hours of organized sports/month; p=0.55). The incidence of injuries was 10.2 per 1,000 competitive exposures [95% CI: 3.7 to 28.4] in the standard-of-care group compared to 3.4 per 1,000 competitive exposures [95% CI: 0.9 to 13.4] in the NMT intervention group. Conclusion: A NMT intervention initiated after post-concussion return-to-play clearance provided significant efficacy in reducing time-loss sport-related injuries over the subsequent year. NMT interventions may be feasibly applied by sports medicine clinicians as a part of return-to-play protocols after concussion to minimize injury risk. Given the relatively small sample size, the findings should be considered preliminary until further definitive trials can be conducted within different geographical locations and/or age groups.Table 1. Comparison of NMT intervention and standard-of-care participant characteristics.Figure 2. Injury free survival in the standard-of-care and NMT intervention groups.
| S-EPMC9112684 | biostudies-literature
Project description:BackgroundMigraine is one of the most common types of headache, and it is the second most common cause of neurological disorders, with an annual prevalence of about 15% of the population. This study aimed to evaluate the effect of BoNT-A on the duration and intensity of migraine attacks. In addition, we investigated the effective injection sites.MethodsAccording to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, we searched online databases, including Web of Science, PubMed, EMBASE, Scopus, Cochrane Library, ProQuest, ClinicalTrials.gov, and Google Scholar from 2011 to 2021.ResultsA total of 24 articles were included in the study. The use of BoNT-A in individuals suffering from chronic migraine (CM) decreases the frequency of migraine attacks per month, pain intensity, medication use, emergency visits, and migraine-related disabilities. The BoNT-A was well tolerated and leads to improved performance and better quality of life (QoL). Overall, treatment with BoNT-A in adults with CM is beneficial. In addition, the use of BoNT-A in individuals with vestibular migraine (VM) reduces the frequency of migraines and brings about the improvement of disability status caused by migraine headaches. Meanwhile, the use of BoNT-A reduces the frequency of migraine attacks per month among individuals with chronic refractory migraine (CRM).ConclusionsThe use of BoNT-A is a low-cost option for the treatment of various kinds of migraines, including chronic, episodic, unilateral, and vestibular types. BoNT-A can reduce the frequency of migraine attacks per month and diminish the severity of pain.
| S-EPMC8989603 | biostudies-literature