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The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled analysis.

ABSTRACT: 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.

SUBMITTER: Matharu M

PROVIDER: S-EPMC5539058 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled analysis.

Matharu Manjit M Halker Rashmi R Pozo-Rosich Patricia P DeGryse Ronald R Manack Adams Aubrey A Aurora Sheena K SK

The journal of headache and pain 20170801 1

<h4>Background</h4>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.<h4>Methods</h4>Data from the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trial program (a 24-week, 2-t ...[more]

PMID: 28766236

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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:IntroductionThe phase 3 PREEMPT trials demonstrated efficacy and tolerability of onabotulinumtoxinA for headache prevention in adults with chronic migraine. OnabotulinumtoxinA significantly reduced headache frequency from baseline vs. placebo at 24 weeks; however, this measure may not fully capture the benefits of treatment. We evaluated the impact of onabotulinumtoxinA on patient-reported outcomes according to headache responder status.MethodsA post hoc analysis pooled 24-week data from the placebo-controlled, randomized, double-blind treatment phases of the PREEMPT trials. Patients were stratified by randomized treatment (onabotulinumtoxinA vs. placebo) and headache day responder status (responder vs. nonresponder). Headache day responders had a ≥ 50% headache day reduction from baseline measured at weeks 21-24. Outcomes evaluated were patient-reported reductions in moderate-to-severe headache days, Headache Impact Test, and Migraine-Specific Quality of Life Questionnaire. Missing values were estimated using a modified last-observation-carried-forward approach.ResultsIn the pooled analysis population (N = 1384; onabotulinumtoxinA, n = 688; placebo, n = 696), headache day responder rates were 308/688 (45%) for onabotulinumtoxinA- and 238/696 (34%) for placebo-treated patients. At 24 weeks compared with baseline, onabotulinumtoxinA nonresponders showed significantly (all P < 0.01) greater mean (standard error) reductions vs. placebo nonresponders in moderate-to-severe headache days (- 3.5 [0.2] vs. - 2.4 [0.2]) and Headache Impact Test scores (- 2.3 [0.3] vs. - 0.8 [0.2]), and greater mean improvements in Migraine-Specific Quality of Life Questionnaire domains (Restrictive, 8.8 [1.0] vs. 2.9 [0.8]; Preventive, 6.0 [1.0] vs. 1.8 [0.8]; Emotional, 8.5 [1.3] vs. 2.8 [1.1]). Moderate-to-severe headache day and headache impact differences between nonresponder groups were evident at week 4 and sustained through week 24.ConclusionsRelative to placebo nonresponders, onabotulinumtoxinA nonresponders experienced significant reductions in moderate-to-severe headache days and disability and improvement in quality of life, implying that the full benefits of onabotulinumtoxinA are not captured by headache day reduction.Trial registrationClinicalTrials.gov identifiers, NCT00156910 (PREEMPT 1) and NCT00168428 (PREEMPT 2).

Project description:IntroductionMigraine is the most common neurological disorder and one of the major causes of years lived with disability. Its treatment (especially of chronic forms) is often challenging and accompanied with adverse effects. Although new therapeutic approaches have recently emerged (eg, calcitonin gene-related peptide antibodies), these are linked to strict prescribing guidelines and therefore limited to only a minority of patients. Recently, randomised controlled trials have demonstrated that open-label placebo treatments can lead to significant and clinically relevant improvements of chronic pain conditions.Methods and analysisThis multicentre, randomised controlled clinical trial following a parallel group between-subject design aims to systematically investigate the impact of a 12-week open-label placebo treatment on moderate to severe headache days (primary outcome) in patients with episodic and chronic migraine in addition to treatment as usual. Secondary outcomes comprise the number of migraine days, pain intensity, intake of acute medication, quality of life, disability, global impression of change, tolerability and a responder rate. To systematically address potential predictors of placebo responses in patients with migraine, this study assesses potential psychometric predictors, salivary cortisol and alpha-amylase awakening responses, catechol-o-methyltransferase Val158Met polymorphisms, as well as functional and structural brain connectivity (ie, resting state functional MRI, diffusion tensor imaging). The data analysis will be performed on basis of the general linear model considering repeated measures (mixed model).Ethics and disseminationThis protocol and all corresponding documents were approved with regard to their content and compliance with ethical regulations by the Ethics Committee of the Medical Faculty of the University Duisburg-Essen, Germany and the Ethics Committee of the Landesärztekammer Hessen. The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numberGerman Clinical Trials Register (DRKS00021259).

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.

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The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled analysis.

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The impact of onabotulinumtoxinA on severe headache days: PREEMPT 56-week pooled analysis.

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