Journal ArticleDOI
OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Analyses of the 56-Week PREEMPT Clinical Program
Sheena K. Aurora,Paul Winner,Marshall C. Freeman,Egilius L.H. Spierings,Jessica O. Heiring,Ronald E. DeGryse,Amanda M. VanDenburgh,Marissa E. Nolan,Catherine C. Turkel +8 more
TLDR
The objective is to evaluate safety and efficacy of onabotulinumtoxinA (BOTOX®) as headache prophylaxis in adults with chronic migraine.Abstract:
Objective.— To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX®) as headache prophylaxis in adults with chronic migraine.
Background.— Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. OnabotulinumtoxinA is the only approved prophylactic therapy in this highly disabled patient population.
Design and Methods.— Two phase III, 24-week, double-blind, parallel-group, placebo-controlled studies, followed by a 32-week, open-label, single-treatment, onabotulinumtoxinA phase, were conducted (January 23, 2006 to August 11, 2008). Qualified subjects were randomized (1:1) to injections of onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for 5 cycles (double-blind: 2, open-label: 3). The pooled primary variable was mean change from baseline in frequency of headache days. Secondary variables included proportion of patients with severe Headache Impact Test-6 score (≥60) and mean changes from baseline in frequencies of migraine days, moderate/severe headache days, and migraine episodes; cumulative hours of headache on headache days; and acute headache medication intakes. The primary time point was week 24. Assessments for the open-label phase (all patients treated with onabotulinumtoxinA) compared double-blind treatment groups (onabotulinumtoxinA/onabotulinumtoxinA vs placebo/onabotulinumtoxinA) and are summarized to give a descriptive view of consistent study results, with inferences regarding statistical significance only examined for week 56.
Results.— A total of 1384 patients were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696) in the double-blind phase; 607 (88.2%) onabotulinumtoxinA/onabotulinumtoxinA and 629 (90.4%) placebo/onabotulinumtoxinA patients continued into the open-label phase. OnabotulinumtoxinA/onabotulinumtoxinA treatment statistically significantly reduced headache-day frequency vs placebo/onabotulinumtoxinA in patients with chronic migraine at week 56 (−11.7 onabotulinumtoxinA/onabotulinumtoxinA, −10.8 placebo/onabotulinumtoxinA; P = .019). Statistically significant reductions also favored onabotulinumtoxinA/onabotulinumtoxinA for several secondary efficacy variables at week 56, including frequencies of migraine days (−11.2 onabotulinumtoxinA/onabotulinumtoxinA, −10.3 placebo/onabotulinumtoxinA; P = .018) and moderate/severe headache days (−10.7 onabotulinumtoxinA/onabotulinumtoxinA, −9.9 placebo/onabotulinumtoxinA; P = .027) and cumulative headache hours on headache days (−169.1 onabotulinumtoxinA/onabotulinumtoxinA, −145.7 placebo/onabotulinumtoxinA; P = .018). After the open-label phase (all treated with onabotulinumtoxinA), statistically significant within-group changes from baseline were observed for all efficacy variables. Most patients (72.6%) completed the open-label phase; few discontinued because of adverse events. No new safety or tolerability issues emerged.
Conclusions.— Repeated treatment with ≤5 cycles of onabotulinumtoxinA was effective, safe, and well tolerated in adults with chronic migraine.read more
Citations
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Journal ArticleDOI
Chronic migraine: risk factors, mechanisms and treatment.
Arne May,Laura H. Schulte +1 more
TL;DR: The pathophysiology of migraine chronification can be understood as a threshold problem: certain predisposing factors, combined with frequent headache pain, lower the threshold of migraine attacks, thereby increasing the risk of chronic migraine.
Journal ArticleDOI
Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study
Marcelo E. Bigal,David W. Dodick,Alan M. Rapoport,Stephen D. Silberstein,Yuju Ma,Ronghua Yang,Pippa S. Loupe,Rami Burstein,Lawrence C. Newman,Richard B. Lipton +9 more
TL;DR: TEV-48125, at doses of 225 mg and 675 mg given once every 28 days for 12 weeks, was safe, well tolerated, and effective as a preventive treatment of high-frequency episodic migraine, thus supporting advancement of the clinical development programme to phase 3 clinical trials.
Journal ArticleDOI
Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study
Marcelo E. Bigal,Lars Edvinsson,Alan M. Rapoport,Richard B. Lipton,Egilius L.H. Spierings,Hans-Christoph Diener,Rami Burstein,Pippa S. Loupe,Yuju Ma,Ronghua Yang,Stephen D. Silberstein +10 more
TL;DR: Efficacy endpoints were change from baseline in the number of headache-hours during the third treatment cycle (weeks 9-12) and safety and tolerability during the study, thus supporting the further development of TEV-48125 for the preventive treatment of chronic migraine in a phase 3 trial.
Journal ArticleDOI
Episodic and Chronic Migraine Headache: Breaking Down Barriers to Optimal Treatment and Prevention
TL;DR: Identifying persons who require migraine prophylaxis and selecting and initiating the most appropriate treatment strategy may prevent progression from episodic to chronic migraine and alleviate the pain and suffering associated with frequent migraine.
Journal ArticleDOI
Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial
Daniel A. Leffler,Ciaran P. Kelly,Peter H.R. Green,Richard N. Fedorak,Anthony J. DiMarino,Wendy Perrow,Henrik S. Rasmussen,Chao Wang,Premysl Bercik,Natalie M. Bachir,Joseph A. Murray +10 more
TL;DR: This study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a gluten-free diet, and results were mixed.
References
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Journal ArticleDOI
The International Classification of Headache Disorders: 2nd edition
A Randomized Double-blind Placebo-controlled Trial
TL;DR: The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferons.
Journal ArticleDOI
Prevalence and Burden of Migraine in the United States: Data From the American Migraine Study II
TL;DR: The prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 population‐based study employing identical methods are described.
Journal ArticleDOI
New Appendix Criteria Open for a Broader Concept of Chronic Migraine
Jes Olesen,Marie-Germaine Bousser,Hans-Christoph Diener,David W. Dodick,M. First,Peter J. Goadsby,H. Gobel,Miguel J. A. Láinez,James W. Lance,Richard B. Lipton,G. Nappi,F Sakai,Jean Schoenen,Stephen D. Silberstein,Timothy J. Steiner +14 more
TL;DR: The International Headache Classification Committee has worked out the more inclusive criteria for CM and MOH and it is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication over use.
Journal ArticleDOI
OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial
Hans-Christoph Diener,David W. Dodick,Sheena K. Aurora,Catherine C. Turkel,Ronald E. DeGryse,Richard B. Lipton,Stephen D. Silberstein,MF Brin,MF Brin +8 more
TL;DR: Significant reductions from baseline were observed for onabotulinumtoxinA for headache and migraine days, cumulative hours of headache on headache days and frequency of moderate/severe headache days, which in turn reduced the burden of illness in adults with disabling chronic migraine.
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