A Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot Study

Background.— There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective.— To compare the efficacy and safety of onabotulinumtoxinA (BOTOX^®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX^®, Ortho‐McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods.— In this single‐center, double‐blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed‐site and 100 U follow‐the‐pain), plus an oral placebo, or topiramate, 4‐week titration to 100 mg/day with option for additional 4‐week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9‐point scale (+4 = clearance of signs and symptoms and ?4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT‐6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4‐week screening period and a 2‐week optional final safety visit. Follow‐up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results.— Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment‐related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between‐group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi‐square). In both groups, HA/migraine days decreased and MIDAS and HIT‐6 scores improved. Patient‐reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ≥50% reduction in HA/migraine days. Forty‐one treatment‐related AEs were reported in 18 onabotulinumtoxinA‐treated patients vs 87 in 25 topiramate‐treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions.— OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations.     

Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program

Chronic migraine (CM) is a prevalent and disabling neurological disorder. Few prophylactic treatments for CM have been investigated. OnabotulinumtoxinA, which inhibits the release of nociceptive mediators, such as glutamate, substance P, and calcitonin gene-related peptide, has been evaluated in randomized, placebo-controlled studies for the preventive treatment of a variety of headache disorders, including CM. These studies have yielded insight into appropriate patient selection, injection sites, dosages, and technique. Initial approaches used a set of fixed sites for the pericranial injections. However, the treatment approach evolved to include other sites that corresponded to the location of pain and tenderness in the individual patient in addition to the fixed sites. The Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) injection paradigm uses both fixed and follow-the-pain sites, with additional specific follow-the-pain sites considered depending on individual symptoms. The PREEMPT paradigm for injecting onabotulinumtoxinA has been shown to be safe, well-tolerated, and effective in well-designed, controlled clinical trials and is the evidence-based approach recommended to optimize clinical outcomes for patients with CM.     

Botulinum toxin in urology: a review of clinical potential in the treatment of urologic and sexual conditions

Introduction: In recent years, there has been an increased interest in the use of botulinum neurotoxin (BoNT) to treat medical conditions refractory to conventional treatment. The following article provides an overview of the clinical use and efficacy of BoNT in the treatment of various urologic and sexual conditions.

Areas covered: BoNT has been accepted and/or explored as novel treatment for various lower urinary tract and sexual dysfunctions such as overactive bladder/detrusor overactivity (DO), detrusor-sphincter dyssynergia (DSD), benign prostatic hyperplasia, interstitial cystitis/painful bladder syndrome, chronic pelvic pain and more recently premature ejaculation. The following terms ‘botulinum toxin’, ‘BoNT’, ‘botulinum toxin A’, ‘Botox’, ‘Dysport’, ‘Xeomin’, ‘botulinum toxin B’, ‘Myobloc’, ‘OnabotulinumA’, ‘RimabotulinumA’, ‘IncobotulinumA’ and ‘AbobotulinumA’ were used to search several databases including MEDLINE, Pubmed, EMBASE, CINAHL and clinicaltrials.gov for inclusion in this review article. Only English language articles were considered and all studies were limited to BoNT therapy in urological conditions in the adult population.

Expert opinion: BoNT-A has received regulatory approval for use in neurogenic DO and overactive bladder, but its use remains unlicensed in other lower urinary tract conditions such as non-neurogenic lower urinary tract symptoms in men with benign prostatic hyperplasia, bladder pain syndrome and DSD. Published literature shows that BoNT can be effective in carefully selected patient groups, has minimal adverse event profile and is generally well tolerated by many patients. However, many questions remain unanswered and larger scale multi-institutional studies are required to determine the key factors in BoNT treatment success.     

Chronic migraine: a therapeutic challenge for clinicians

Chronic migraine is a common disabling condition. Severe migraine attacks should be treated with triptans, but these agents are contraindicated in patients with vascular problems and may not be effective or tolerated in around one third of the patients. New acute migraine therapies without vasoconstrictive activity and triptan-specific side effects are emerging. For the prophylaxis of chronic migraine, only topiramate and OnabotulinumtoxinA have been shown to be effective in placebo-controlled randomized trials, so novel therapeutic strategies are needed. The growing understanding of the pathophysiology of chronic migraine will contribute to the identification of new treatment targets.