Dataset Information

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.

ABSTRACT:

Background

Chronic migraine (CM) is associated with high impact and reduced health-related quality of life (HRQoL).

Methods

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) groups, respectively). HRQoL endpoints were assessed over 56 weeks using the Headache Impact Test (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ). HIT-6 score reductions ≥2.3 and ≥5 denoted between-group minimally important difference and within-patient clinically meaningful response, respectively.

Results

A total of 1236 participants (O/O, n = 607; P/O, n = 629) participated in both phases. The DB phase showed significantly reduced HIT-6 and MSQ for onabotulinumtoxinA versus placebo (all p < 0.001). The OL phase showed significantly reduced HIT-6 for O/O versus P/O at weeks 28, 36, and 48, but not 56. All three MSQ domains showed improved HRQoL relative to baseline, but only the role restrictive domain showed a significant difference between O/O and P/O at week 56.

Conclusions

Benefits of onabotulinumtoxinA on HRQoL versus baseline persisted throughout the OL phase. Statistical superiority in favor of O/O was demonstrated for HIT-6 through 48 weeks and for MSQ (role restrictive) at 56 weeks.

SUBMITTER: Lipton RB

PROVIDER: S-EPMC4959035 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

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]

PMID: 27288354

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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).

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.

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.

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.

Dataset Information

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.

Background

Methods

Results

Conclusions

Publications

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.

Similar Datasets

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