OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Results From the Double-Blind, Randomized, Placebo-Controlled Phases of the PREEMPT Clinical Program

Department of Neurology, Mayo Clinic Arizona, Phoenix, AZ, USA.
Headache The Journal of Head and Face Pain (Impact Factor: 2.71). 06/2010; 50(6):921-36. DOI: 10.1111/j.1526-4610.2010.01678.x
Source: PubMed


To assess the efficacy, safety, and tolerability of onabotulinumtoxinA (BOTOX) as headache prophylaxis in adults with chronic migraine.
Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. Few preventive treatments have been investigated and none is specifically indicated for chronic migraine.
The 2 multicenter, pivotal trials in the PREEMPT: Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy clinical program each included a 24-week randomized, double-blind phase followed by a 32-week open-label phase ( identifiers NCT00156910, NCT00168428). Qualified patients were randomized (1:1) to onabotulinumtoxinA (155-195 U) or placebo injections every 12 weeks. Study visits occurred every 4 weeks. These studies were identical in design (eg, inclusion/exclusion criteria, randomization, visits, double-blind phase, open-label phase, safety assessments, treatment), with the only exception being the designation of the primary and secondary endpoints. Therefore, the predefined pooling of the results was justified and performed to provide a complete overview of between-group differences in efficacy, safety, and tolerability that may not have been evident in individual studies. The primary endpoint for the pooled analysis was mean change from baseline in frequency of headache days at 24 weeks. Secondary endpoints were mean change from baseline to week 24 in frequency of migraine/probable migraine days, frequency of moderate/severe headache days, total cumulative hours of headache on headache days, frequency of headache episodes, frequency of migraine/probable migraine episodes, frequency of acute headache pain medication intakes, and the proportion of patients with severe (> or =60) Headache Impact Test-6 score at week 24. Results of the pooled analyses of the 2 PREEMPT double-blind phases are presented.
A total of 1384 adults were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696). Pooled analyses demonstrated a large mean decrease from baseline in frequency of headache days, with statistically significant between-group differences favoring onabotulinumtoxinA over placebo at week 24 (-8.4 vs -6.6; P < .001) and at all other time points. Significant differences favoring onabotulinumtoxinA were also observed for all secondary efficacy variables at all time points, with the exception of frequency of acute headache pain medication intakes. Adverse events occurred in 62.4% of onabotulinumtoxinA patients and 51.7% of placebo patients. Most patients reported adverse events that were mild to moderate in severity and few discontinued (onabotulinumtoxinA, 3.8%; placebo, 1.2%) due to adverse events. No unexpected treatment-related adverse events were identified.
The pooled PREEMPT results demonstrate that onabotulinumtoxinA is an effective prophylactic treatment for chronic migraine. OnabotulinumtoxinA resulted in significant improvements compared with placebo in multiple headache symptom measures, and significantly reduced headache-related disability and improved functioning, vitality, and overall health-related quality of life. Repeat treatments with onabotulinumtoxinA were safe and well tolerated.

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    • "The PREEMPT clinical trials showed that OnabotulinumtoxinA is a safe, well-tolerated, and effective prophylactic therapy for CM patients[13,14]. To date, the PREEMPT clinical program is the largest (1384 patients) and longest (24-week, double-blind period followed by a 32-week, open-label phase) study in CM[15]. Its remarkable results led to the worldwide specific indication of OnabotulinumtoxinA for the prevention of headache in CM patients[16]. "
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    ABSTRACT: The efficacy and safety of OnabotulinumtoxinA (BOTOX®) in adults with chronic migraine (CM) were demonstrated in the PREEMPT program. However, the dosage used in this study was flexible from 155 U to 195 U at the physician’s discretion. Therefore, the objective of this prospective study was to compare the efficacy and safety of OnabotulinumtoxinA 195 U vs. 155 U for the treatment of CM and medication overuse headache (MOH) during a 2-year period. We prospectively evaluated the mean reduction in headache days, migraine days, acute pain medication intake days and Headache Impact Test (HIT)-6 score in 172 patients injected with OnabotulinumtoxinA 195 U. Successively, we compared the efficacy measures with data of 155 patients injected with OnabotulinumtoxinA 155 U and followed up for 2 years. All patients were affected by CM and MOH, and failed one or more previous detoxification and preventative therapies. Both OnabotulinumtoxinA 195 U and 155 U reduced significantly the number of headache and migraine days, acute pain medication intake days and HIT-6 score, when compared with the baseline measures. Nevertheless, OnabotulinumtoxinA 195 U proved to be superior of 155 U in all efficacy measures since the first injection and for all the 2 years of treatment, with the exception of the reduction in pain medication intake days that resulted significantly larger with 195 U only after the 4th injection. The safety and tolerability of the two doses were similar and treatment related adverse events were transient and mild-moderate. This study represents the largest and longest post-marketing studies of doses comparison with OnabotulinumtoxinA in a real-life clinical setting. Here, we demonstrate the superior efficacy of OnabotulinumtoxinA 195 U compared to 155 U in CM patients with MOH during a 2-year treatment period with similar safety and tolerability profile.
    Full-text · Article · Dec 2015 · The Journal of Headache and Pain
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    • "The efficacy and safety of OnabotulinumtoxinA in adults with chronic migraine was shown in the phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical programme [18,26-29]. These data led to the licensing authorities granting approval for this toxin in chronic migraine. "
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    ABSTRACT: Background Chronic migraine affects 2% of the population. It results in substantial disability and reduced quality of life. Medications used for prophylaxis in episodic migraine may also work in chronic migraine. The efficacy and safety of OnabotulinumtoxinA (BOTOX) in adults with chronic migraine was confirmed in the PREEMPT programme. However, there are few real-life data of its use. Method 254 adults with chronic migraine were injected with OnabotulinumtoxinA BOTOX as per PREEMPT Protocol between July 2010 and May 2013, their headache data were collected using the Hull headache diary and analysed to look for headache, migraine days decrements, crystal clear days increment in the month post treatment, we looked at the 50% responder rate as well. Results Our prospective analysis shows that OnabotulinumtoxinA, significantly, reduced the number of headache and migraine days, and increased the number of headache free days. OnabotulinumtoxinA Botox also improved patients’ quality of life. We believe that these results represent the largest post-marketing cohort of patients treated with OnabotulinumtoxinA in the real-life clinical setting. Conclusion OnabotulinumtoxinA is a valuable addition to current treatment options in patients with chronic migraine. Our results support findings of PREEMPT study in a large cohort of patients, we believe, is representative of the patients seen in an average tertiary headache centre. While it can be used as a first line prophylaxis its cost may restrict its use to more refractory patients who failed three oral preventive treatments.
    Full-text · Article · Sep 2014 · The Journal of Headache and Pain
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    • "Most individuals with primary CDH report headaches with migrainous features.2,4,5,6,7 The close association between migraine and CDH has prompted proposals for the chronic migraine (CM) criteria.8,9,10 Although CDH is a common problem in clinical practice, no population-based data on CDH have yet been reported in Korea. "
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    ABSTRACT: Background and Purpose Chronic daily headache (CDH) is a commonly reported reason for visiting hospital neurology departments, but its prevalence, clinical characteristics, and management have not been well documented in Korea. The objective of this study was to characterize the 1-year prevalence, clinical characteristics, medical consultations, and treatment for CDH in Korea. Methods The Korean Headache Survey (KHS) is a nationwide descriptive survey of 1507 Korean adults aged between 19 and 69 years. The KHS investigated headache characteristics, sociodemographics, and headache-related disability using a structured interview. We used the KHS data for this study. Results The 1-year prevalence of CDH was 1.8% (95% confidence interval, 1.1-2.5%), and 25.7% of the subjects with CDH met the criteria for medication overuse. Two-thirds (66.7%) of CDH subjects were classified as having chronic migraine, and approximately half of the CDH subjects (48.1%) reported that their headaches either substantially or severely affected their quality of life. Less than half (40.7%) of the subjects with CDH reported having consulted a doctor for their headaches and 40.7% had not received treatment for their headaches during the previous year. Conclusions The prevalence of CDH was 1.8% and medication overuse was associated with one-quarter of CDH cases in Korea. Many subjects with CDH do not seek medical consultation and do not receive appropriate treatment for their headaches.
    Full-text · Article · Jul 2014 · Journal of Clinical Neurology
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