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PD1-01 LONG-TERM EFFICACY AND SAFETY OF ONABOTULINUMTOXINA IN PATIENTS WITH NEUROGENIC DETRUSOR OVERACTIVITY: ANALYSIS AMONG PATIENTS WHO COMPLETED 4 YEARS OF TREATMENT
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
Urodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction I Podium 1 Friday, May 15, 2015
10:30 AM-12:30 PM
PD1-01 LONG-TERM EFFICACY AND SAFETY OF ONABOTULINUMTOXINA IN PATIENTS WITH NEUROGENIC DETRUSOR OVERACTIVITY: ANALYSIS AMONG PATIENTS WHO COMPLETED 4 YEARS OF TREATMENT Eric Rovner*, Charleston, SC; Alfred Kohan, Bethpage, NY; €nemann, Kiel, Emmanuel Chartier-Kastler, Paris, France; Klaus-Peter Ju Germany; Giulio Del Popolo, Florence, Italy; Sender Herschorn, Toronto, Canada; Manher Joshi, Brenda Jenkins, Irvine, CA; Quanhong Ni, Bridgewater, NJ; Victor Nitti, New York, NY INTRODUCTION AND OBJECTIVES: Long-term outcomes following repeat onabotulinumtoxinA (onabotA) injections for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO) are not well studied. We performed a post-hoc analysis to assess efficacy/ safety outcomes in patients who completed 4 years of onabotA treatment. METHODS: Patients (pts) who completed a 52-week phase 3 study of intradetrusor onabotA for treatment of UI due to NDO were eligible to enter a 3-year extension study in which they could receive multiple onabotA treatments (some pts received 200U for all treatments, while others received 300U and switched to 200U following FDA approval). A total of 227 pts completed the entire 4-year study; this analysis includes data from pts who only received onabotA 200U (n¼122). Efficacy/safety assessments included mean change from baseline (at week 6) in number of daily UI episodes and IncontinenceQuality of Life (I-QOL) total summary score, proportions of pts with 50% and 100% reduction in daily UI episodes, overall median duration of effect, adverse events (AEs), and initiation of de novo clean intermittent catheterization (CIC). Outcomes were assessed by year of treatment. For each patient, the mean value for each 6 week outcome measure was calculated from all treatments received in a given year. The overall cohort mean for the year was then calculated. RESULTS: Pts received an average of 1.5, 1.4, 1.5, and 1.5 onabotA treatments/year in years 1e4. Reductions in the mean number of UI episodes/day were consistent from year 1e4 following onabotA treatment (-3.4, -3.6, -3.8, and -3.7 UI episodes/day, respectively). The majority of pts (88e90%) achieved 50% reduction in UI episodes/day in each year of treatment, and 44e52% of pts experienced 100% reduction. Improvements in I-QOL total scores were consistently 2e3X greater than the minimal important difference (þ11 points) in each year of treatment. Overall median time for pts to request their next treatment was 9.2 months. The most common AE across all groups was UTI with no increase in incidence over time. Among pts who had never catheterized at the start of each year, rates of initiating de novo CIC were 39% (18/46 pts), 11% (3/28 pts), 8% (2/25 pts) and 0% (0/23 pts) (years 1, 2, 3, 4, respectively). CONCLUSIONS: NDO pts who completed 4 years of treatment with onabotA experienced long-term treatment benefit, with consistent improvements year to year in daily UI episodes and QOL; no new safety signals were observed over time. Source of Funding: Supported by Allergan, Inc.
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PD1-02 EFFECT OF DETRUSOR BOTULINUM TOXIN AINJECTION ON THE UROTHELIAL DYSFUNCTION IN CHRONIC SPINAL CORD INJUREDBLADDERS ¡V COMPARISON AMONG BASELINE, 3 MONTHS AND 6 MONTHS AFTER INJECTION Sheng-Fu Chen*, Cheng-Ling Lee, Jia-Hui Chang, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Botulinum toxin A (BoNT-A) has been demonstrated effective in treatment of neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) patients. The aim of this study is to investigate the changes of urothelial junction proteins, apoptosis and suburothelial inflammation at baseline, 3 and 6 months after treatment. METHODS: A total of 26 patients with chronic suprasacral SCI and refractory NDO were enrolled. The urothelium was assessed by cold-cup biopsy at baseline, 3 and 6 months after 300 U BoNT-A detrusor single injections. Immunofluorescence staining of E-cadherin, zonulaoccludens (ZO-1), tryptase for mast cell activation and TUNEL assay for urothelial apoptosis were performed. The differences of the urothelial dysfunction were compared between baseline and 3 months and 6 months after BoNT-A injection. Bladder biopsy from patients undergoing anti-incontinence surgery served as controls. RESULTS: Detrusor BoNT-A injection significantly decreased detrusor pressure and increased bladder compliance at 3 and 6 months after treatment. A significantly lower E-cadherin and ZO-1 expression and increased mast cell counts and apoptotic cells were noted in SCI bladders compared with controls (all P<0.001) (Table 1). Significantly higher distribution of E-cadherin (p<0.001) and ZO-1 (p¼0.05) expressions were noted at 3 months after BoNT-A injection compared to the baseline. However, these changes of E-cadherin and ZO-1 declined at 6 months. The activated mast cells and urothelial apoptosis showed no significant difference between baseline and 3 or 6 months (Fig. 1). CONCLUSIONS: This is the first study to assess the effect of BoNT-A on the urothelial dysfunction in SCI patients. The defective adhesive and junction protein concentrationsin SCI bladders might be recovered after BoNT-A injection. However, this effect would decrease as time goes by. The neurogenic inflammation after SCI could not be adequately relieved after single BoNT-A injection.
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
Urodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction I Podium 1 Friday, May 15, 2015
10:30 AM-12:30 PM
PD1-01 LONG-TERM EFFICACY AND SAFETY OF ONABOTULINUMTOXINA IN PATIENTS WITH NEUROGENIC DETRUSOR OVERACTIVITY: ANALYSIS AMONG PATIENTS WHO COMPLETED 4 YEARS OF TREATMENT Eric Rovner*, Charleston, SC; Alfred Kohan, Bethpage, NY; €nemann, Kiel, Emmanuel Chartier-Kastler, Paris, France; Klaus-Peter Ju Germany; Giulio Del Popolo, Florence, Italy; Sender Herschorn, Toronto, Canada; Manher Joshi, Brenda Jenkins, Irvine, CA; Quanhong Ni, Bridgewater, NJ; Victor Nitti, New York, NY INTRODUCTION AND OBJECTIVES: Long-term outcomes following repeat onabotulinumtoxinA (onabotA) injections for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO) are not well studied. We performed a post-hoc analysis to assess efficacy/ safety outcomes in patients who completed 4 years of onabotA treatment. METHODS: Patients (pts) who completed a 52-week phase 3 study of intradetrusor onabotA for treatment of UI due to NDO were eligible to enter a 3-year extension study in which they could receive multiple onabotA treatments (some pts received 200U for all treatments, while others received 300U and switched to 200U following FDA approval). A total of 227 pts completed the entire 4-year study; this analysis includes data from pts who only received onabotA 200U (n¼122). Efficacy/safety assessments included mean change from baseline (at week 6) in number of daily UI episodes and IncontinenceQuality of Life (I-QOL) total summary score, proportions of pts with 50% and 100% reduction in daily UI episodes, overall median duration of effect, adverse events (AEs), and initiation of de novo clean intermittent catheterization (CIC). Outcomes were assessed by year of treatment. For each patient, the mean value for each 6 week outcome measure was calculated from all treatments received in a given year. The overall cohort mean for the year was then calculated. RESULTS: Pts received an average of 1.5, 1.4, 1.5, and 1.5 onabotA treatments/year in years 1e4. Reductions in the mean number of UI episodes/day were consistent from year 1e4 following onabotA treatment (-3.4, -3.6, -3.8, and -3.7 UI episodes/day, respectively). The majority of pts (88e90%) achieved 50% reduction in UI episodes/day in each year of treatment, and 44e52% of pts experienced 100% reduction. Improvements in I-QOL total scores were consistently 2e3X greater than the minimal important difference (þ11 points) in each year of treatment. Overall median time for pts to request their next treatment was 9.2 months. The most common AE across all groups was UTI with no increase in incidence over time. Among pts who had never catheterized at the start of each year, rates of initiating de novo CIC were 39% (18/46 pts), 11% (3/28 pts), 8% (2/25 pts) and 0% (0/23 pts) (years 1, 2, 3, 4, respectively). CONCLUSIONS: NDO pts who completed 4 years of treatment with onabotA experienced long-term treatment benefit, with consistent improvements year to year in daily UI episodes and QOL; no new safety signals were observed over time. Source of Funding: Supported by Allergan, Inc.
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PD1-02 EFFECT OF DETRUSOR BOTULINUM TOXIN AINJECTION ON THE UROTHELIAL DYSFUNCTION IN CHRONIC SPINAL CORD INJUREDBLADDERS ¡V COMPARISON AMONG BASELINE, 3 MONTHS AND 6 MONTHS AFTER INJECTION Sheng-Fu Chen*, Cheng-Ling Lee, Jia-Hui Chang, Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Botulinum toxin A (BoNT-A) has been demonstrated effective in treatment of neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) patients. The aim of this study is to investigate the changes of urothelial junction proteins, apoptosis and suburothelial inflammation at baseline, 3 and 6 months after treatment. METHODS: A total of 26 patients with chronic suprasacral SCI and refractory NDO were enrolled. The urothelium was assessed by cold-cup biopsy at baseline, 3 and 6 months after 300 U BoNT-A detrusor single injections. Immunofluorescence staining of E-cadherin, zonulaoccludens (ZO-1), tryptase for mast cell activation and TUNEL assay for urothelial apoptosis were performed. The differences of the urothelial dysfunction were compared between baseline and 3 months and 6 months after BoNT-A injection. Bladder biopsy from patients undergoing anti-incontinence surgery served as controls. RESULTS: Detrusor BoNT-A injection significantly decreased detrusor pressure and increased bladder compliance at 3 and 6 months after treatment. A significantly lower E-cadherin and ZO-1 expression and increased mast cell counts and apoptotic cells were noted in SCI bladders compared with controls (all P<0.001) (Table 1). Significantly higher distribution of E-cadherin (p<0.001) and ZO-1 (p¼0.05) expressions were noted at 3 months after BoNT-A injection compared to the baseline. However, these changes of E-cadherin and ZO-1 declined at 6 months. The activated mast cells and urothelial apoptosis showed no significant difference between baseline and 3 or 6 months (Fig. 1). CONCLUSIONS: This is the first study to assess the effect of BoNT-A on the urothelial dysfunction in SCI patients. The defective adhesive and junction protein concentrationsin SCI bladders might be recovered after BoNT-A injection. However, this effect would decrease as time goes by. The neurogenic inflammation after SCI could not be adequately relieved after single BoNT-A injection.