Intravesical onabotA instillation safe, but with no clear benefit in urinary incontinence

The intravesical instillation of onabotulinumtoxinA (onabotA) for refractory overactive bladder in urinary incontinence is generally safe and well-tolerated, but demonstrates no significant efficacy advantage over placebo, according to a recent study.

The study included 252 participants who were randomly assigned to receive 100- (n=50), 300- (n=53), 400- (n=50) and 500-U (n=50) onabotA doses or placebo (n=49). In all groups, the treatment was admixed with a hydrogel and delivered via instillation. The primary endpoint of interest was the 12-week change in the number of urinary incontinence episodes; secondary outcomes included micturition, urinary urgency, and nocturia episodes per day.

After 12 weeks, the number of incontinence episodes dropped in all groups. The least squares (LS) mean change values from baseline ranged from –0.9 to –1.9 episodes per day across the three onabotA groups. These were not significantly better than that in placebo comparators, which saw an LS mean change of –2.7 urinary incontinence episodes per day from baseline. [J Urol 2022;doi:10.1097/JU.0000000000002800]

Similarly, secondary efficacy endpoints could not significantly differentiate onabotA instillation from placebo. At 12 weeks, the proportion of patients with a ≥50-percent reduction in daily incontinence episodes ranged from 46.9 percent to 53.8 percent across all three instillation groups, as opposed to 65.2 percent in placebo counterparts.

In addition, the number of daily micturition episodes per day had LS mean changes ranging from –0.9 to –1.1 episodes per day in the onabotA groups as compared with an LS mean change of –1.6 episodes per day in placebo controls. Similar trends were reported for nocturia episodes per day and volume per void.

Nevertheless, the intravesical instillation approached proved safe. The proportion of participants with treatment-emergent adverse events ranged from 43.1 percent to 63.3 percent in the onabotA groups, none of which were significantly higher than the 43.9-percent emergence rate in the placebo group. Asymptomatic bacteriuria was the most common side effect reported, arising in 6.7 percent to 15.5 percent of patients across all treatment groups.

“Delivery of an admixture of onabotA and hydrogel via instillation is expected to allow for prolonged drug residence time in the bladder. This could result in a more accessible, simpler, and convenient mode of administration compared to injections, and may lead to lower rates of urinary retention and urinary tract infection,” the researchers said.

However, the present study found no significant efficacy benefit to such an approach, which often yielded symptomatic improvements that were of lower magnitude than those observed in the placebo group.

“The observed lack of efficacy was perhaps due to onabotA size being too large to diffuse across the urothelium. Future injection-free studies for the delivery of onabotA to the bladder should focus on a more effective delivery method,” the researchers added.