Chronic migraine (CM) is a severely disabling neurological condition characterized by episodes of pulsating unilateral or bilateral headache. The United States Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox) for the prophylactic treatment of CM in 2010. It has been shown that onabotulinumtoxinA is effective in the reduction of headache frequency and severity in patients with CM. Treatment is well tolerated by the patients. This review reports on the history of botulinum neurotoxin (BoNT) in CM and presents the current clinical evidence for the use of onabotulinumtoxinA in the treatment of CM.

Botulinum toxin (BT) therapy is the treatment of choice for blepharospasm (BPS). Currently available BT type A drugs include Botox(®), Dysport(®) and Xeomin(®). Until now, there are few long-term studies on BT therapy for BPS. This is the first long-term study comparing all three major BT drugs. We collected treatment, efficacy and adverse effect data on BPS patients treated with either Botox(®), Dysport(®) or Xeomin(®) for at least eight consecutive treatments. Two hundred and eighty-eight patients (208 females, 80 males, age 62 ± 12 years) were included in this study. The treatment time was 11.2 ± 4.1 years covering 10,701 injection series. Doses were 47 ± 10 MU for Botox(®), 120 ± 35 MU for Dysport(®) and 62 ± 11 MU for Xeomin(®) (Botox(®) dose vs Xeomin(®) dose: p < 0.001, unpaired t test). 85 % of all patients had stable doses. The onset of the therapeutic effect was after 6.1 ± 3.3 days and its duration lasted 10.2 ± 3.5 weeks. The Global Clinical Improvement (GCI, 0 = no, 1 = slight, 2 = moderate, 3 = marked improvement in severity and function) as estimated by the patient was 2.5 ± 0.6. It was stable in 90% of the patients. Adverse effect frequency was 3.0% (ptosis 2.3%, dry eye 0.5%, diplopia 0.2%). None of these findings was significantly different between Botox(®), Dysport(®) and Xeomin(®). Our study, one of the largest studies on BT therapy of BPS and the study with the longest follow-up, confirms that BT therapy produces robust clinical improvement which is stable throughout the treatment time. Therapeutic effects start after 6.1 days and last for about 10 weeks before they start to vanish. With this, they are approximately 2 weeks shorter than the recommended inter-injection interval. Adverse effects were rare, mild and always transient. BT therapy is a safe and effective treatment for BSP. Shorter inter-injection intervals may improve therapeutic results.

These data confirm the efficacy and safety of BoNT-A treatment in CD over an extended period of up to 14 years.

Botulinum toxin is considered the treatment of choice for hemifacial spasm (HFS) and reinnervation synkinesias (RS). We present 133 patients with HFS (n = 97) and RS (n = 36) who have been treated with either Botox (n = 78) or Dysport (n = 55) exclusively for 6 years (range 2-12 years). The Botox dose was 21 +/- 8 MU, the Dysport dose 46 +/- 22 MU. The therapeutic effect started after 7.1 +/- 2.3 days and lasted for 12.5 +/- 3.9 weeks. It was stable throughout the observation period in 85% of all patients. Adverse effects occurred in 5.4% of injection series. No patient terminated treatment because of unsatisfactory results. Secondary therapy failure did not occur. With an effective conversion ratio of Botox:Dysport = 1:2.56 there were no differences between both drugs with respect to therapeutic efficacy and adverse effects thus confirming the hypothesis that there may not be intrinsic differences between both products.

Botulinum toxin (BT) used for dystonia and spasticity is dosed according to the number of target muscles and the severity of their muscle hyperactivities. With this no other drug is used in a broader dose range than BT. The upper end of this range, however, still needs to be explored. We wanted to do this by a prospective non-interventional study comparing a randomly selected group of dystonia and spasticity patients receiving incobotulinumtoxinA (Xeomin(®)) high-dose therapy (HD group, n = 100, single dose ≥400 MU) to a control group receiving incobotulinumtoxinA regular-dose therapy (RD group, n = 30, single dose ≤200 MU). At the measurement point all patients were evaluated for systemic BT toxicity, i.e. systemic motor impairment or systemic autonomic dysfunction. HD group patients (56.1 ± 13.8 years, 46 dystonia, 54 spasticity) were treated with Xeomin(®) 570.1 ± 158.9 (min 400, max 1,200) MU during 10.2 ± 7.0 (min 4, max 37) injection series. In dystonia patients the number of target muscles was 46 and the dose per target muscle 56.4 ± 19.1 MU, in spasticity patients 35 and 114.9 ± 67.1 MU. HD and RD group patients reported 58 occurrences of items on the systemic toxicity questionnaire. Generalised weakness, being bedridden, feeling of residual urine and constipation were caused by the underlying tetra- or paraparesis, blurred vision by presbyopia. Dysphagia and dryness of eye were local BT adverse effects. Neurologic examination, serum chemistry and full blood count did not indicate any systemic adverse effects. Elevated serum levels for creatine kinase/MB, creatine kinase and lactate dehydrogenase were most likely iatrogenic artefacts. None of the patients developed antibody-induced therapy failure. Xeomin(®) can be used safely in doses ≥400 MU and up to 1,200 MU without detectable systemic toxicity. This allows expanding the use of BT therapy to patients with more widespread and more severe muscle hyperactivity conditions. Further studies-carefully designed and rigorously monitored-are necessary to explore the threshold dose for clinically detectable systemic toxicity.

Botulinum toxin was shown to be effective in treatment of chronic migraine. We wanted to explore its efficacy and tolerability in chronic application under real-life conditions. For this, 27 consecutive patients (age 45.6 ± 10.8 years, 25 females, 2 males) received altogether 176 injection series (IS) with 189.7 ± 45.8MU onabotulinumtoxinA (Botox(®)) according to the PREEMPT scheme. During the study period altogether 6.5 ± 2.9 (min 4, max 13) IS were applied per patient (total treatment time of 73.1 ± 36.9 weeks). 96 % of the patients reported benefit. Monthly headache days were reduced from 18.9 ± 3.9 to 8.7 ± 4.5 (p < 0.001, -53.7 %), migraine days from 16.8 ± 4.9 to 7.4 ± 4.6 (p < 0.001, -55.1 %), autonomic days from 8.6 ± 7.5 to 2.7 ± 4.2 (p < 0.001, -71.9 %) and medication days from 14.2 ± 4.6 to 8.3 ± 4.2 (p < 0.001, -71.1 %). Health-related quality of life improved by 0.6-1.5 standard deviations (SD) (Short Form Health Survey), migraine-related quality of life by 1.4-2.0 SD (Migraine-Specific Quality of Life Questionnaire) and by 1.9 SD (Headache Impact Test), depression by 1.1 SD (Beck Depression Inventory). Subjective global clinical improvement was 2.6 ± 0.6 (Global Clinical Improvement Scale). All improvements were stable throughout the entire study period. Adverse effects were infrequent, mild and transient. Botulinum toxin provides highly effective and safe long-term treatment of chronic migraine.

Our data confirm the safety and efficacy of BoNT-A treatment of spasticity of different etiologies over a long period of time. Furthermore, the data imply that BoNT-A treatment should be started early after appearance of spasticity to obtain better treatment response.

Background Chronic 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. Methods REPOSE 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. Results Overall, 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. Conclusions Real-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 registration NCT01686581. Name of registry: ClinicalTrials.gov. URL of registry: Date of retrospective registration: September 18, 2012. Date of enrolment of first patient: July 23, 2012.