What is the efficacy and safety of botulinum toxin injections to treat neurogenic detrusor overactivity?

Updated: Mar 06, 2019
  • Author: Pamela I Ellsworth, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Kuo, in a study assessing whether suburothelial injection of different doses of botulinum toxin A would have a similar therapeutic effect to but less side effects than the use of 200 U botulinum toxin-A in patients with refractory detrusor overactivity, found that a dose of 100 U, compared with 150 or 200 U, achieved a similar rate of excellent results and had significantly fewer adverse events; the dose also affected the duration of therapeutic effectiveness. [2]

In this study, 75 patients were enrolled and randomized to receive 100, 150, or 200 U botulinum toxin-A injected suburothelially at 40 sites. [2] Of the 75, 40 had NDO. Of these 40, 22 had chronic cerebrovascular accidents or Parkinson disease and 18 a spinal cord injury or multiple sclerosis. All patients voided by reflex or abdominal stimulation and had baseline postvoid residual volumes smaller than 150 mL.

When patients with NDO were compared with those with idiopathic detrusor overactivity (IDO), the former had significantly greater rates of excellent (patient achieved continence with a voiding difficulty grade increased by less than 2) and improved (incontinence grade improved by 1 or more points compared to baseline and voiding difficulty increased by less than 2) results (97.5% versus 77.1%).

When NDO and IDO patients were considered together, cystometric bladder capacity at 1 month increased by 1.8 times, 1.73 times, and 1.56 times the baseline value for patients treated with 200, 150, and 100 U of botulinum toxin A, respectively; capacity at 3 months increased by 1.5, 1.4, and 1.3 times the baseline value. [2] Mean postvoid residual volume increased by 3-4 times the baseline value at 1 month in all treatment groups and remained significantly increased at 3 months in patients who received 150 and 200 U of botulinum toxin A.

A randomized, double-blind phase III study by Tullman et al reported that onabotulinumtoxinA significantly reduced urinary incontinence at week 6 compared to the placebo in noncatheterizing patients with multiple sclerosis. The study also reported that 53% of patients treated with onabotulinumtoxinA achieved 100% reduction of urinary incontinence comparted to 10.3% in the placebo group. Significant improvements in quality of life and lower clean intermittent catheterization rates than were previously reported were also seen. [3]

 

Schurch et al, in a double-blind, randomized, placebo-controlled, parallel-group study aimed at determining the safety and efficacy of 200 and 300 U botulinum toxin A injections into the detrusor in patients with NDO (primarily related to spinal cord injury [SCI]), found that such injections provided rapid, well-tolerated, clinically significant decreases in the signs and symptoms of urinary incontinence. [4]

In this study, 59 patients (53 with SCI and 6 with multiple sclerosis) with NDO and incontinence requiring clean intermittent catheterization were randomized to either 200 or 300 U of botulinum toxin A or to placebo. [4] Endpoints included changes in daily frequency of urinary incontinence episodes (primary endpoint), urodynamic parameters, and impact on quality of life (QoL) as determined by the Incontinence Quality of Life questionnaire.

Significant posttreatment decreases in incontinence episodes from baseline occurred in both treatment groups but not in the placebo group. [4] Significant decreases in incontinence episodes at all time points were seen in the 2 botulinum toxin A groups (except for weeks 12 and 18 in the 200 U group) but not in the placebo group. Compared with placebo, the difference between treatment groups was significantly in favor of the 300 U group at weeks 2 and 6 and the 200 U group at week 24. Anticholinergic use remained similar throughout.

The mean maximal cystometric bladder capacity increased significantly from baseline in each botulinum toxin A treatment group at all posttreatment time points, although no significant changes were noted in the placebo group. [4] Mean changes from baseline in the 2 treatment groups were significantly higher as compared with the placebo group at every time point except week 24 in the 300 U group.

The overall incidence of patients experiencing at least 1 adverse event was not significantly different among the treatment groups, and no such events were considered to be related to the study group. [4] No cases of autonomic dysreflexia were noted.

Giannantoni et al evaluated the effectiveness and safety of intravesical resiniferatoxin and botulinum toxin A injections into the detrusor muscle in a group of SCI patients with NDO unresponsive to conventional anticholinergic therapy and found that botulinum A toxin injections provided superior clinical and urodynamic benefits. [5]

In this study, 25 patients were randomly assigned to receive either resiniferatoxin 0.6 µM diluted in 30 mL of 0.9% sodium chloride or intradetrusor injections of botulinum toxin A 300 U diluted in 30 mL 0.9% sodium chloride. [5] Patients were asked to decrease the daily dosage of anticholinergics within 15 days of the beginning of treatment.

The frequency of incontinence episodes in the botulinum toxin A arm significantly decreased compared with the resiniferatoxin arm at 6, 12, and 18 months’ follow-up. [5] In addition, the uninhibited detrusor contractions threshold and the maximum bladder capacity significantly increased; the maximum pressure of uninhibited detrusor contractions in the botulinum toxin A arm significantly decreased as compared to the resiniferatoxin arm at 6, 12, and 18 months’ follow-up.

The investigators did not identify any local side effects during and after intradetrusor injections. [5] One patient experienced mild asthenia soon after the first treatment, which persisted for 10 days. Seven patients in the botulinum toxin A arm continued to take anticholinergics during follow-up, but the dosage was decreased by an average of 62.5% compared with 10 patients who continued anticholinergic therapy during the entire observation; dosage in the resiniferatoxin group decreased by an average of 56.4%.

A study by Kim et al reported that preoperative bladder compliance and open bladder neck were important predictors of outcome after botulinum toxin-A intradetrusor injection. [6]

A study by Peyronnet et al found that after failure of a first detrusor injection of botulinum toxin for neurogenic detrusor overactivity, a switch to a different toxin seems to be more effective than a second injection of the same toxin. [7]


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