Overactive Bladder (OAB)
First line therapy for OAB are behavioral therapy, biofeedback and physical therapy. 2nd line treatment is oral medications. Sacral neuromodulation, PTNM and Botox are next line therapy. Patients treated with 82% have therapeutic success at 5 years and 86% at 1 year, defined as >50% reduction in number of voids per day (or less than 8) or >50% reduction in number of daily leak episodes.(2)
OAB resolves spontaneously sometimes, as shown when 480 men with nonneurogenic OAB were evaluated. One in three older men with non-neurogenic OAB had sustained remission of symptoms without medical or surgical interventions. No significant predictor of sustained remission was identified. (1)
ONABOTULINUMTOXIN A
A RCT of 21 patients observing intratrigonal onabotulinumtoxinA showed they had significantly reduced pain at 12 weeks compared with saline (mean ± SD –3.8 ± 2.5 vs –1.6 ± 2.1, p <0.05). The proportion of patients who achieved a 50% or greater reduction in the pain visual analog scale was 60% for onabotulinumtoxinA vs 22% for placebo. Urinary tract infections developed in 3 patients who received onabotulinumtoxinA vs 2 who received saline. Mean post-void residual urine at week 12 was 5 ± 13 ml for onabotulinumtoxinA vs 0 ml with saline. This study had the limitations inherent to a single center trial with a small number of patients enrolled. The authors conclude that onabotulinumtoxinA 100 U caused significant and clinically relevant improvements in bladder pain and quality of life in patients with bladder pain syndrome/interstitial cystitis refractory to common therapy. (3) A meta-analysis comparing mirabegron with botox showed botox had a higher rate of UTI but more effective at reducing number of micturations and incontinent episodes. (7)
Several studies have given rates of retention, however depending on the definition of retention determines the rate. One study found a rate of CIC of 1.6% based on their definition of retention requiring CIC. (8) \
A small study showed comparable efficacy using 3-4 injection sites of botox. (9)
MIRABEGRON AND SOLIFENACIN COMBO
FDA approved combo therapy of mirabegron and solifenacin in 2018 based on the SYNERGY I, SYNERGY II and BESIDE studies.
SYNERGY I - 6,991 patients, 435 locations, 42 countries. Combo of mirabegron and solifenacin succinate compared with each drug as monotherapy and placebo in patients w/ wet OAB for at least 3 months. (4)
SYNERGY II - 2,084 patients, 251 locations, 32 countries. Combination of mirabegron 50 mg and solifenacin succinate 5 mg compared with each drug as monotherapy in patients who had experienced symptoms of "wet" OAB for at least 3 months. (5)
BESIDE - 2,174 patients, 281 locations, 31 countries. Mirabegron 50 mg as an add-on therapy with solifenacin succinate 5 mg versus solifenacin succinate 5 mg and 10mg alone in OAB patients who had inadequate response to treatment with solifenacin succinate monotherapy. (6)
OAB resolves spontaneously sometimes, as shown when 480 men with nonneurogenic OAB were evaluated. One in three older men with non-neurogenic OAB had sustained remission of symptoms without medical or surgical interventions. No significant predictor of sustained remission was identified. (1)
ONABOTULINUMTOXIN A
A RCT of 21 patients observing intratrigonal onabotulinumtoxinA showed they had significantly reduced pain at 12 weeks compared with saline (mean ± SD –3.8 ± 2.5 vs –1.6 ± 2.1, p <0.05). The proportion of patients who achieved a 50% or greater reduction in the pain visual analog scale was 60% for onabotulinumtoxinA vs 22% for placebo. Urinary tract infections developed in 3 patients who received onabotulinumtoxinA vs 2 who received saline. Mean post-void residual urine at week 12 was 5 ± 13 ml for onabotulinumtoxinA vs 0 ml with saline. This study had the limitations inherent to a single center trial with a small number of patients enrolled. The authors conclude that onabotulinumtoxinA 100 U caused significant and clinically relevant improvements in bladder pain and quality of life in patients with bladder pain syndrome/interstitial cystitis refractory to common therapy. (3) A meta-analysis comparing mirabegron with botox showed botox had a higher rate of UTI but more effective at reducing number of micturations and incontinent episodes. (7)
Several studies have given rates of retention, however depending on the definition of retention determines the rate. One study found a rate of CIC of 1.6% based on their definition of retention requiring CIC. (8) \
A small study showed comparable efficacy using 3-4 injection sites of botox. (9)
MIRABEGRON AND SOLIFENACIN COMBO
FDA approved combo therapy of mirabegron and solifenacin in 2018 based on the SYNERGY I, SYNERGY II and BESIDE studies.
SYNERGY I - 6,991 patients, 435 locations, 42 countries. Combo of mirabegron and solifenacin succinate compared with each drug as monotherapy and placebo in patients w/ wet OAB for at least 3 months. (4)
SYNERGY II - 2,084 patients, 251 locations, 32 countries. Combination of mirabegron 50 mg and solifenacin succinate 5 mg compared with each drug as monotherapy in patients who had experienced symptoms of "wet" OAB for at least 3 months. (5)
BESIDE - 2,174 patients, 281 locations, 31 countries. Mirabegron 50 mg as an add-on therapy with solifenacin succinate 5 mg versus solifenacin succinate 5 mg and 10mg alone in OAB patients who had inadequate response to treatment with solifenacin succinate monotherapy. (6)
- Noguchi, Naomi, et al. "Natural history of non‐neurogenic overactive bladder and urinary incontinence over 5 years in community‐dwelling older men: The concord health and aging in men project." Neurourology and urodynamics 36.2 (2017): 443-448.
- Siegel, Steven, et al. "Five-year followup results of a prospective, multicenter study of patients with overactive bladder treated with sacral neuromodulation." The Journal of urology 199.1 (2018): 229-236.
- Pinto, Rui Almeida, et al. "Intratrigonal Onabotulinum Toxin A Improves Bladder Symptoms and Quality of Life in Bladder Pain Syndrome/Interstitial Cystitis Patients: A Pilot, Single Center, Randomized, Double-Blind, Placebo Controlled Trial." The Journal of urology (2017).
- Herschorn S, Chapple CR, Abrams P, et al. Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study). BJU Int 2017;120(4):562-75.
- ClinicalTrials.gov. A Randomized, Double-Blind, Parallel-Group, Active-Controlled, Multi-center Study to Evaluate the Long-Term Safety and Efficacy of Combination of Solifenacin Succinate With Mirabegron Compared to Solifenacin Succinate and Mirabegron Monotherapy in Subjects With Overactive Bladder (09-21-2017). https://clinicaltrials.gov/ct2/show/study/NCT02045862. Accessed 02-22-2018.
- Drake MJ, Chapple C, Esen AA, et al. Efficacy and safety of mirabegron add-on therapy to solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4-week solifenacin monotherapy: a randomised double-blind multicentre phase 3B study (BESIDE). Eur Urol 2016;70(1):136-45.
- Lozano-Ortega, G., Walker, D., Rogula, B., Deighton, A., Johnston, K., Hawkins, N., & Dmochowski, R. (2019). The Relative Efficacy and Safety of Mirabegron and OnabotulinumtoxinA in Patients With Overactive Bladder who Have Previously Been Managed With an Antimuscarinic: A Network Meta-analysis. Urology.
- Patel, Devin N., et al. “What Is the True Catheterization Rate after Intravesical OnabotulinumtoxinA Injection.” International Urogynecology Journal, vol. 29, no. 7, 2018, pp. 1005–1009.
- Martínez-Cuenca, Esther, et al. "Onabotulinumtoxina Re-Injection for Refractory Detrusor Overactivity Using 3-4 Injection Sites: Results of a Pilot Study." Urology (2019).