Botox can be used in adults with neurogenic detrusor overactivity due to subcervical spinal cord injury (traumatic or non-traumatic) or multiple sclerosis (MS), who are not adequately managed with anticholinergics. Patients should be already catheterised or willing and able to catheterise if required.
Two randomised, double-blind, placebo-controlled, phase III studies assessed the efficacy and safety of Botox in this setting; the first enrolled 419 patients and the second enrolled 275 patients. Participants were randomised to receive 200 Units of toxin (n=227), 300 Units of toxin (n=223), or placebo (n=241).
Assessment at 6 weeks showed that weekly incontinence episodes (the primary endpoint) had declined by 20.0 in the 200 Unit group compared with 10.5 in the placebo group (p<0.001), from a baseline of 32.4 and 31.5, respectively. Maximum cystometric capacity increased significantly more with Botox than placebo (+140.4ml for the 200 Unit dose vs +6.9ml). The median duration of response (defined as a <50% reduction in incontinence episodes) was 42 weeks with the 200 Unit dose. No clinically relevant benefit was identified for the 300 Unit dose over the 200 Unit dose.
For all efficacy endpoints, patients experienced a consistent response on re-treatment (n=116). Investigators detected no neutralising antibodies after one or two treatments in any of the 475 patients analysed.
In the patients with MS, the annualised MS exacerbation rate (ie, the number of MS exacerbation events per patient year) was 0.23 in the 200 Unit group and 0.20 in the placebo group. With repeated treatments, including data from a long-term study, the exacerbation rate was 0.19 during each of the first two treatment cycles.