Results from a Phase 3 clinical trial show that urinary symptoms can be reduced significantly after treatment with low-dose Botox (100 units) in patients with multiple sclerosis (MS).
That finding was reported in the study “Low-dose onabotulinumtoxinA improves urinary symptoms in noncatheterizing patients with MS,” published in the journal Neurology.
Most patients with MS develop neurogenic detrusor overactivity (NDO). The detrusor muscles are part of the bladder and are involved in bladder contractions. Because of nerve damage caused by MS, the communication between the spinal cord and the bladder is disrupted and the detrusor muscles become overactive. This results in sporadic and frequent urine leakage. Not surprisingly, NDO can severely affect MS patients’ quality of life.
Treatments for NDO are usually invasive, and may include surgery and the use of implantable devices.
Botox (onabotulinumtoxinA), a minimally invasive option, is approved for the treatment of NDO associated with MS. Studies have shown that injections of Botox (200 units) can reduce urinary incontinence and improve the patient’s quality of life. However, high doses of Botox are associated with a potential risk of complications, including urinary retention requiring clean intermittent catheterization (the insertion of a catheter into the bladder to help the person urinate).
A previous Phase 3 trial (NCT00910845) testing Botox in patients with idiopathic overactive bladder with urinary incontinence (non-MS patients) showed that Botox at 100 units (half the dose) could reduce urinary incontinence.
In 2015, researchers completed a Phase 3 trial (NCT01600716) to assess the safety and effectiveness of Botox (marketed by Allergan) at a dose of 100 units in noncatheterizing patients with MS and urinary incontinence due to NDO, to determine if the lower dose could reduce urinary symptoms in these patients.
The trial included 144 noncatheterized patients with clinically stable MS, and a history of NDO for more than three months. These patients were recruited from 58 sites across North America and Europe between July 2012 and March 2015.
In total, 66 patients received 1 mL injections of Botox (100 units) distributed evenly into the detrusor muscle, while 78 patients received injections of a placebo. Patients were followed for 52 weeks (one year), with check-ups at 2, 6, 12, 24, and 52 weeks.
Significant decreases in urinary incontinence episodes in patients treated with Botox were seen as early as two weeks after the injection. This trend continued through week 12. At week six, more patients treated with Botox reported a more than 50% reduction or total reduction in urinary incontinence episodes per day, compared to patients treated with placebo.
Botox treatment also increased the maximum cystometric capacity — referring to the volume at which the patient feels he/she can no longer delay urination — compared to placebo, and significantly decreased the pressure in detrusor muscles.
Results showed that while symptoms of urinary incontinence decreased, bladder function improved.
Regarding incontinence-related quality of life, greater improvements were seen in patients treated with Botox.
Importantly, treatment with Botox was long-lasting. Duration of Botox’s effect (i.e., median time until request for another treatment) was 51.7 weeks, compared to only 12.6 weeks in patients treated with placebo. Only 45.5% of patients treated with Botox requested a second dose, while 85.9% of patients treated with placebo requested a second treatment.
Botox was generally well-tolerated, and adverse effects for this treatment were low. The most common adverse event reported was urinary tract infection (25.8%).
Overall, the team concluded “in noncatheterizing patients with MS and NDO, treatment with onabotulinumtoxinA 100 [units] results in significant and clinically relevant improvements in UI [urinary incontinence] and other urinary symptoms, urodynamics, and QOL [quality of life]…than previously reported with onabotulinumtoxinA 200 U,” they wrote.
The team also emphasized that “more than half the patients (53%) treated with onabotulinumtoxinA became incontinence free (i.e., “dry”) at week 6 after treatment.”
Of note, the study was funded by Allergan, and the results are specific to the Botox formulation used. Other botulinum toxin products may not have the same results.