Low-Dose Botox May Reduce Urinary Symptoms in Patients With Multiple Sclerosis

Symptoms of urinary incontinence (UI) in patients with multiple sclerosis (MS) can be alleviated via treatment with low-dose onabotulinumtoxinA (Botox) injections, according to a phase 3 trial.

The study, published in Neurology, noted that the majority of patients with MS develop neurogenic detrusor overactivity (NDO). The MS patient population can frequently develop demyelinating lesions above the level of the pons or in reticulospinal pathways, which can cause uninhibited bladder contractions that result in urinary urgency, frequent micturition, and UI, the authors wrote.

The trial recruited 144 noncatheterized patients between July 2012 and March 2015 with clinically stable MS who experienced NDO for more than 3 months. Patients’ NDO symptoms were inadequately managed by an anticholinergic, defined as either an inadequate response after more than 4 weeks of treatment or intolerable adverse effects (AEs) following 2 weeks of therapy with an optimized dose.

Sixty-six patients were randomized to receive 1-mL injections of Botox (100 units) administered evenly into the detrusor muscle and 78 patients received a placebo. Patients were followed for 52 weeks, with follow up at weeks 2, 6, 12, 24, and 52. The primary endpoint of the trial was the mean change in UI episodes per day from baseline at week 6.

The researchers observed a significant reduction in UI episodes in patients treated with Botox as early as 2 weeks following the injection, which continued through week 12. At 6 weeks, more patients administered Botox experienced a greater than 50% reduction or total reduction in UI episodes per day compared with the placebo group, according to the study.

Treatment with Botox was also found to improve urinary urgency and the point that patients can no longer delay urination compared with placebo. The treatment not only reduced the symptoms of UI, but also improved bladder function, according to the study.

The Botox treatment group also experienced greater improvements in incontinence-related quality of life (QOL) across all 3 measures—avoidance and limiting behavior, psychosocial impact, and social embarrassment.

The duration of efficacy was reported as 51.7 weeks in the Botox group compared with 12.6 weeks in the placebo cohort, with 45.5% of patients in the Botox cohort requesting a second dose versus 85.9% of patients in the placebo group.

AEs were mostly limited to the urinary tract, with the most commonly reported AE being urinary tract infections (UTI), which were experienced in 25.8% of Botox-treated patients and 6.4% of patients in the placebo group.

Notably, since the study was funded by Allergan and only evaluated Botox, the results may not be similar with other botulinum toxin treatments, which are not interchangeable.

“This trial demonstrates that in noncatheterizing patients with MS and NDO, treatment with onabotulinumtoxinA 100 U results in significant and clinically relevant improvements in UI and other urinary symptoms, urodynamics, and QOL with lower [clean intermittent catheterization] and UTI rates than previously reported with onabotulinumtoxinA 200 U,” the authors concluded.

Reference

Tullman M, Chartier-Kastler E, Kohan A, et al. Low-dose onabotulinumtoxinA improves urinary symptoms in noncatheterizing patients with MS. Neurology. 2018.

doi:10.1212/WNL.0000000000005991