Intravesical onabotulinumtoxinA (Botox) reduces bladder pain in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), two separate studies show.
Hualien, Taiwan-Intravesical onabotulinumtoxinA (Botox) reduces bladder pain in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), two separate studies show.
According to the results of a randomized, controlled trial presented at the AUA annual meeting in New Orleans, botulinum injections improved clinical symptoms, increased bladder capacity, and provided pain relief in patients who were refractory to conventional treatment.
“The results of this clinical trial demonstrated that intravesical injection of 100 U Botox effectively reduced bladder pain and increased bladder capacity in patients with IC/BPS refractory to treatment. Rates of adverse events are acceptable and they are manageable,” said Yuan-Hong Jiang, MD, a urologist at Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
Although botulinum injections have been demonstrated to be beneficial for the treatment of IC/BPS, therapeutic efficacy has not been validated by a placebo-controlled study. For this trial, the authors recruited IC/BPS patients refractory to conventional treatment.
Sixty patients were randomized in a 2:1 ratio across 20 sites to receive hydrodistention plus intravesical suburothelial injection of botulinum, 100 U, or the equivalent amount of normal saline. The primary endpoint was a decrease in pain assessed using a visual analogue scale (VAS) at week 8 after treatment.
“At week 8,” said Dr. Jiang, “we observed a significantly greater decrease of VAS in the Botox group compared to the normal saline group. Cystometric bladder capacity and post-void residual urine also showed greater increase in the Botox group.”
According to Dr. Jiang, the overall success rates were 63% in the botulinum group and 15% in the control. There was no significant difference in the prevalence of adverse events between the groups.
A separate, pilot study, also presented at the AUA annual meeting, evaluated safety and feasibility of intravesical instillation of Botox in hydrogel-based slow-release delivery system. That approach also showed promise of pain relief for IC/BPS patients.
“The results suggest that intravesical instillation of the novel TCGel and Botox mixture is both safe and tolerable,” reported Amnon Zisman, MD, head of urology at the Assaf-Harofeh Medical Center in Zerrifin, Israel. “No worsening of symptoms was detected.”
The single-arm prospective study included 15 patients (11 females and four males), who received a single intravesical instillation of botulinum, 200 U, premixed with TCGel, 40 mL through a 12F urethral catheter. Median patient age was 48 years, with a body mass index of 26.4 kg/m2.
As Dr. Zisman explained, TCGel (TheraCoat Ltd.), instilled as cold fluid at 4 °C, solidifies in the bladder within 10 minutes and dissolves gradually in urine.
“An intravesical instillation of a mixture of TCGel and Botox is an appealing alternative to intra-detrusor injection,” he said. “There is an increase in active drug dwell time in the bladder in spite of frequent emptying. Therefore, it acts as a slow-release formulation.”
Bladder pain was measured using a VAS, 3-day bladder diary, and the O’Leary-Sant questionnaire. Assessment was reported prior to installation and 2, 6, and 12 weeks after.
All adverse events were recorded according to study protocol
“Interestingly,” said Dr. Zisman, “26% of study subjects reported mild constipation. This adverse event was also reported in other studies where Botox was injected into the bladder wall.”
In the entire group study, a significant pain reduction was noted 2 weeks following instillation. A statistically significant reduction in O’Leary-Sant Symptom and Problem Indexes was shown at all checkpoints. There was also tendency for reduction, although not significant, in the mean number of voids per night and in the mean number of urge episodes per day, he reported.
While these findings suggest sustained efficacy, Dr. Zisman concluded that further investigation would require a group being treated with a sham procedure.
Theracoat, Ltd. provided funding for Dr. Zisman’s study. Dr. Zisman’s co-authors are consultants/advisers for or employees of Theracoat.