Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long‐term extension study

Aims

To present final efficacy/safety results from a prospective, long‐term extension trial of onabotulinumtoxinA for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO); patients received treatment for up to 4 years.

Methods

Patients who completed a 52‐week, phase III trial of onabotulinumtoxinA for NDO were eligible to enter a 3‐year, multicenter, open‐label extension study of intradetrusor onabotulinumtoxinA (200U or 300U). Patients were treated “as needed” based on their request and fulfillment of prespecified qualification criteria (≥12 weeks since previous treatment and a UI episode threshold). Assessments included change from study baseline in UI episodes/day (primary efficacy measure), volume/void, and Incontinence Quality of Life (I‐QOL) total score (week 6); duration of effect; adverse events (AEs); and initiation of de novo clean intermittent catheterization (CIC). Data are presented for up to six treatments.

Results

OnabotulinumtoxinA 200U consistently reduced UI episodes/day; reductions from baseline ranged from –3.2 to –4.1 across six treatments. Volume/void consistently increased, nearly doubling after treatment. I‐QOL improvements were consistently greater than twice the minimally important difference (+11 points). Overall median duration of effect was 9.0 months (200U). Results were similar for onabotulinumtoxinA 300U. Most common AEs were urinary tract infections and urinary retention. De novo CIC rates were 29.5, 3.4, and 6.0% (200U), and 43.0, 15.0, and 4.8% (300U) for treatments 1–3, respectively; de novo CIC rates were 0% for treatments 4–6.

Conclusions

OnabotulinumtoxinA treatments consistently improve UI, volume/void, and QOL in patients with UI due to NDO in this 4‐year study, with no new safety signals. Neurourol. Urodynam. 36:368–375, 2017. © 2015 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.     

Insights into the mechanism of onabotulinumtoxinA in chronic migraine

OnabotulinumtoxinA has recently been approved by regulatory agencies in the UK and United States for treatment of chronic migraine based on data generated from the PREEMPT studies. As such, onabotulinumtoxinA is the only prophylactic therapy specifically approved for chronic migraine. Most headache clinicians would agree that acute episodic migraine and chronic migraine differ in their pathophysiology, etiology, diagnosis, and response to pharmacological as well as nonpharmacological therapies. Of the 7 botulinum neurotoxin serotypes, botulinum neurotoxin type A (onabotulinumtoxinA) has been the most thoroughly investigated in preclinical and clinical studies. Based on preclinical studies, onabotulinumtoxinA is known to inhibit the release of excitatory neurotransmitters from both motor and sensory neurons by preventing vesicle fusion to the cell membrane. In addition to the well-documented myorelaxant effects of this neurotoxin, onabotulinumtoxinA can exert a direct analgesic effect that likely involves inhibition of primary and secondary nociceptive neurons. The inhibitory effects of onabotulinumtoxinA are also likely to involve suppressing the activity of myogenic trigger points and decreasing the persistent nociceptive barrage that promotes and maintains central sensitization. This article describes possible mechanisms to explain how onabotulinumtoxinA functions as a therapy for chronic migraine and considers why treatment with the neurotoxin is not effective in some chronic migraineurs.     

Trajectory of health care resources among adults stopping or reducing treatment frequency of botulinum toxin for chronic migraine treatment in Alberta,Canada

Objective

Understand health resource, medication use, and cost of adults with chronic migraine who received guideline-recommended onabotulinumtoxinA (botulinum toxin) treatment frequency and then continued or reduced/stopped.

Background

Botulinum toxin may be a beneficial treatment for chronic migraine; the trajectory of health resources utilization among those with continued or reduced/stopped use is unclear.

Methods

A retrospective population-based cohort study utilizing administrative data from Alberta, Canada (2012–2020), was performed. A cohort of adults who received ≥5 botulinum toxin treatment cycles for chronic migraine over 18 months (6-month run-in; 1-year pre-index period) were grouped into those who (1) continued use (≥3 treatments/year), or (2) stopped or reduced use (stopped for 6 months then received 0 or 1–2 treatments/year, respectively) over a 1-year post-index period. Health resources and medication use were described, and pre–post costs were assessed. A second cohort that received ≥3 treatments/year immediately followed by 1 year of stopped or reduced use was considered in sensitivity analysis.

Results

Pre–post health resource, medication use, and costs were similar among those with continued use (n = 3336). Among those who stopped or reduced use (n = 1099; 756 stopped, 343 reduced), health resource, medication use, and costs were lower in the post- (total median per-person cost [IQR]: all-cause $4851 [$8090]; migraine-related $835 [$1915]) versus pre- (all-cause $6096 [$7207]; migraine-related $2995 [$1950]) index period (estimated cost ratios [95% CI]: total all-cause 0.86 [0.79, 0.95]; total migraine-related 0.44 [0.40, 0.48]). In the second cohort (n = 3763), return to continued use (≥3 treatments/year) occurred in up to 70.4% in those with reduced use.

Conclusions

Of adults treated with botulinum toxin for chronic migraine, 75.2% had continued use, stable health resource and medication use, and costs over a 2 year period. In those that stopped/reduced use, the observed lower health resource and migraine medication use may indicate improved symptom control, but the resumption of guideline-recommended treatment intervals after reduced use was common.     

Drug-resistant epicrania fugax: Responding to onabotulinumtoxinA

Epicrania fugax (EF) is a primary headache consisting of brief paroxysms of pain, lasting 1–10 s, that move through different nerve territories of one hemicranium with a linear or zigzag trajectory, although there are some clinical variants. Preventive therapy with anti-seizure medication such as gabapentin and lamotrigine are most commonly used in patients presenting with frequent and non-remitting attacks. In some cases, greater occipital nerve blockades are used for short- or long-term relief. Here, we report two patients with a paroxysmal EF-type pain who meet the criteria for EF of the International Classification of Headache Disorders, 3rd edition, with clear triggers and autonomic ocular signs and who failed multiple preventive treatments, but had a sustained response to onabotulinumtoxinA.