1970 COMPARISON STUDY OF ONABOTULINUMTOXINA 300U AND 200U IN PATIENTS WITH DETRUSOR OVERACTIVITY

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Most of the reinterventions (47 %) occurred during the first 2 years of followup. Reintervention rate drops after two years of followup, with exception of battery exchange for depletion which starts to occur after 5 years after implantation. CONCLUSIONS: Data from this retrospective long term followup study, demonstrates a high reintervention rate after Interstim therapy. 41 %of patients needed a surgical reintervention during follow up, with a median reintervention rate of 1.7. 47 % of reinterventions were done the first two years of follow up. Reintervention rate drops after two years of follow up with exception of battery exchange for depletion. Interstim therapy offers a successful therapy in up to 71% of patients refractory to any other therapies. A high reintervention rate is the price for this success. Source of Funding: None

1968 THE ROLE OF URINARY NEUROTROPHIC FACTORS IN OVERACTIVE BLADDER SYNDROME Tiago Antunes-Lopes*, Rui Pinto, Se´rgio Carvalho-Barros, Francisco Botelho, Paulo Diniz, Carlos Martins-Silva, Ce´lia Duarte-Cruz, Francisco Cruz, Porto, Portugal INTRODUCTION AND OBJECTIVES: Most well known neurotrophic factors (NFs) include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). While NGF and BDNF are committed with a peptidergic subpopulation of primary afferents, GDNF is important to maintain the non-peptidergic subpopulation, both in central and peripheral nervous system. The aims of our study were: 1) to investigate urinary levels of NGF, BDNF and GDNF in OAB patients and in healthy controls, 2) to assess urinary levels of NGF, BDNF and GDNF in OAB patients, after lifestyle counseling (LSC) and antimuscarinic treatment (AMT) and 3) to correlate urinary levels of NFs with the severity of symptoms. METHODS: Urine samples from 25 female OAB patients were collected at baseline, 3 months (after LSC) and 6 months (after 3-month AMT: oxybutynin chloride ER, 10 mg/d). Urine samples from 20 healthy women were also collected. Samples were processed for ELISA analysis of NGF, BDNF and GDNF. Urinary content of NFs was normalized against creatinine concentration. All patients completed a 7-day bladder diary combined with modified Indevus Urgency Severity Scale at baseline, 3 months and 6 months. Bladder condition was assessed using the number of urgency episodes per week (NUE/w). RESULTS: At baseline, urinary NGF and BDNF were significantly higher in patients, compared to controls (NGF: 485⫾493 vs 188⫾290, p⫽0.006; BDNF: 792⫾641 vs 110⫾160, p⬍0.001). In contrast, urinary GDNF showed no statistical significant differences between both groups (790⫾788 vs 1220⫾514). After LSC, there was a decrease in urinary NGF (485⫾493 to 320⫾332) and BDNF (792⫾641 to 432⫾589, p⫽0.013). After AMT, NGF decreased to 180⫾238, while BDNF had a further reduction to 147⫾265. At 6 months, NGF and BDNF were significantly lower than at baseline (p⬍0.05). On the contrary, there was no significant variation in GDNF. At baseline, the mean NUE/w was 68⫾9. After LSC, there was a decrease to 56⫾9 (p⬍0.05), and, after AMT, there was a further reduction to 35⫾14 (p⬍0.05). A significant correlation was only found between BDNF and NUE/w variations, from baseline to 6 months (r⫽0.607, p⬍0.01). Using ROC analysis, the area under the curve was higher for BDNF (0.88) compared to NGF (0.75). CONCLUSIONS: In OAB patients, urinary NGF and BDNF levels were significantly higher, compared to controls, while no significant differences were found for GDNF. Urinary NGF and BDNF sig-

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nificantly decreased after AMT. This variation was more pronounced for BDNF. These data suggest NFs as key elements in the pathogenesis of OAB. Source of Funding: Funded by INComb FP7 HEALTH project no 223234

1969 DIABETES MELLITUS DOES NOT AFFECT THE EFFICACY AND SAFETY OF INTRAVESICAL BOTUNILUM TOXIN TYPE A INJECTION ON PATIENTS WITH OAVERACTIVE BLADDER Chung-Cheng Wang*, Taipei, Taiwan; Hann-Chorng Kuo, Hualien, Taiwan INTRODUCTION AND OBJECTIVES: Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). Diabetic patients have more OAB symptoms and may be more refractory to behavioral and pharmacological therapy. Intravesical botulinum toxin type A (BoNTA) injection has been considered as a new therapy option for OAB patients when conventional treatment failed. However, whether diabetes is a poor prognostic factor for BoNTA treatment was not fully understood. Thus, we investigated the efficacy and safety of BoNTA injection for patients with DM and OAB. METHODS: A total of 217 patients who received intravesical BoNTA injection for refractory OAB were enrolled into this study. Of them, 48 patients have DM. Videourodynamics was performed at baseline and was repeated at 3 months after intravesical BoNTA injection. Patients with moderate and marked improved defined as the patient¡s perception of bladder condition improved by 2 and 3 points were considered as exhibiting a successful result. The procedurerelated adverse effects including acute urinary retention, large postvoiding residuals, straining to void, urinary tract infection, hematuria and general weakness were recorded. Forty-eight age-matched patients were randomly selected from non-diabetic groups and compared. RESULTS: The mean age of diabetic and non-diabetic patients were 73.08⫾8.80 and 71.98⫾9.33 (p⫽0.552), respectively. The similar successful results were noted at 6 months follow-up (DM 56% versus non-DM 61%, p⫽0.128). The changes of urodynamic parameters were comparable between two groups. Compared with non-diabetic patients, diabetic patients had significant higher incidence of large post-voiding residuals (60.4% in DM versus 33.3% in non-DM, p⫽ 0.007) and general weakness (10.4% in DM versus 0% in non-DM, p⫽0.03) after BoNTA injection. However, baseline urodynamic parameters in diabetic patients could not predict the happening of adverse effects. No major complications were noted in both groups. CONCLUSIONS: Though intravesical BoNTA injection increased the incidence of large post-voiding residuals and general weakness in diabetic patients, diabetes itself did not influence the treatment outcomes and other adverse effects. BoNTA injection was a safe and effective treatment for patients with OAB and diabetes. Source of Funding: None

1970 COMPARISON STUDY OF ONABOTULINUMTOXINA 300U AND 200U IN PATIENTS WITH DETRUSOR OVERACTIVITY. Manar Malki*, Altaf Mangera, Sheilagh Reid, Richard Inman, Chris Chapple, Sheffield, United Kingdom INTRODUCTION AND OBJECTIVES: OnabotulinumtoxinA (Botox) remains off-license for treating patients with detrusor overactivity (DO) in the UK. Regulatory approval is anticipated in many countries for 200U in patients with neurogenic detrusor overactivity (NDO). The optimum dose for patients with idiopathic detrusor overactivity (IDO) is still undergoing evaluation. METHODS: An earlier study was performed in our urology unit of all the patients that had received 300U onabotulinumtoxinA until June

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2008 (n⫽79). Thereafter since July 2008 we began to inject Botox 200U in all patients with DO. We reviewed the case notes of patients that had received both 200u and 300u to assess differences in outcomes. RESULTS: Forty four patients (36 female and 8 male) had received both 300 and 200U onabotulinumtoxinA, 28 for IDO and 16 for NDO. Of these; 37 patients reported continued improvement with 200U onabotulinumtoxinA, 4 received no benefit and 3 had worsening in their symptoms. Percentage improvement in urgency and urgency incontinence episodes per day were 82% and 72% in patients who were receiving 200U. Table 1 shows a comparison of outcomes for onabotulinumtoxinA 300 and 200U in the same group of patients. Of the 44 patients 39 continued to receive 200U, 4 went back to 300U (decreased effect) and 1 did not attend after the 1st treatment. After switching to 200u three patients were commenced on CISC for de novo voiding difficulty. CONCLUSIONS: 80% of patients were happy with their symptoms after switching form 300 to 200U onabotulinumtoxinA. Only 9% of patients (all with NDO) went back to receiving 300U. This is the first study to compare 200U and 300U onabotulinumtoxinA in the same patients and our results show similar efficacy and longevity in the majority of patients (90%) using 200U in both NDO and IDO. However some patients may require the higher dose of 300U especially with NDO. Parameter % patients with subjective efficacy

NDO 300u

NDO 200u

IDO 300u

IDO 200u

83.3%

93.7%

81.6%

78.5%

Median longevity

4-5 months

4-5 months

6-7 months

6-7 months

Need for catheter

93%

93%

42.9%

53.5%

UTI

23%

37.5%

26.5%

32.1%

Other complications

10%

6.2%

6.1%

7.1%

Table. 1 Outcomes of injecting OnabotulinumtoxinA 300U and 200U in patients with NDO and IDO.

Source of Funding: None

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Future studies with larger groups and longer follow up time are needed to help characterize the utility of BoNT in treating OAB secondary to BPH. Table 1: Baseline characteristics Placebo Botulinum Variable (n⫽6) (n⫽7) Age (years), mean ⫾ SD 66.7 ⫾ 9.6 70 ⫾ 13.2 BMI (lbs/in2), mean ⫾ SD

p-value 0.62

32.7 ⫾ 3.1

26.8 ⫾ 2.3

0.02

21 (9-24)

16 (13-23)

0.72

Baseline IPSS, median (IQR) Baseline irritative IPSS subdomain, median

11.5 (6-13)

10 (7-14)

0.89

Baseline Qmax, (mL/s) mean ⫾ SD

16.4 ⫾ 6.5

21.8 ⫾ 15.4

0.44

Baseline voided volume (mL) mean ⫾ SD

214.3 ⫾ 93.1

227.3 ⫾ 125.8

0.84

PVR (mL), mean ⫾ SD

42.8 ⫾ 35.6

38.3 ⫾ 37.9

0.83

Prostate volume (cm3), mean ⫾ SD

43.3 ⫾ 28.6

87.1 ⫾ 40.1

0.34

Voiding frequency preprocedure, median (IQR)

12 (10-12)

9 (8-12)

0.28

Table 2: Voiding outcomes after BoNT vs. placebo injections in patients with overactive bladder and BPH.

Variable Baseline

Median % Urinary change Frequency from (IQR) baseline

PVR

Median % change from baseline

Qmax

Median % change from baseline

IPSS (IQR)

Placebo 12 (10-12)

42.8 ⫾ 35.6

16.4 ⫾ 6.5

21 (9-24)

BoNTA

9 (8-12)

38.3 ⫾ 37.9

21.8 ⫾ 15.4

16 (13-23)

p-value

0.28

0.83

0.44

Median % change from baseline

0.72

Day 30 Placebo 10 (8-13) BoNTA

9 (9-15)

p-value

0.4

16.7% 0 0.99

166.5 ⫾ 102.6 197% 260 ⫾ 291.4 109%

8.7 ⫾ 3.7

44.7% 18.5 (12-25.5)

⫺3.5%

17.5 ⫾ 10.8

42.3%

0.18

0.64

0.86

30.6% 10.4 ⫾ 3.1

31.2%

20 (10.5-24.5)

14%

19.8 ⫾ 2.2

14.5%

14 (13-21)

⫺5%

⬍0.01

0.48

0.57

0.99

22 (19-23)

⫺43.8% 0.29

Day 90 25 ⫾ 50

1971

Placebo

RANDOMIZED DOUBLE-BLIND PLACEBO CONTROLLED TRIAL OF INTRADETRUSOR INJECTIONS OF BOTULINUM TOXIN FOR THE TREATMENT OF REFRACTORY OVERACTIVE BLADDER SECONDARY TO BENIGN PROSTATIC HYPERPLASIA

BoNTA

87.2 ⫾ 195

p-value

0.56

Daniel J. Lee*, Seema Sheth, Bilal Chughtai, Richard K. Lee, Steven Kaplan, Alexis Te, New York, NY INTRODUCTION AND OBJECTIVES: Options for idiopathic overactive bladder (OAB) refractory to medical and surgical management are limited. We assessed the efficacy of botulinum toxin A (BoNT, Botox®, Allergan, Inc., Irvine, CA) in patients with refractory OAB secondary to benign prostatic hyperplasia (BPH). METHODS: This was a phase III, multi-center, randomized, double-blinded study conducted in 2 institutions. The following data represent the results from a single institution. Inclusion criteria included patients with OAB secondary to BPH, refractory to anticholinergic medication and persistent after surgical intervention to relieve obstruction, with an International Prostate Symptom Score (IPSS)⬎12. Patients were randomized in 1:1 fashion to either 20 injections of intradetrusor 10U BoNT vs. placebo. Six patients received BoNT vs. 7 placebo. Follow-up was performed at 1 week and then 1, 3, 6, and 9 months. Voiding diaries, maximum flow rate (Qmax), post-void residuals (PVR), and IPSS scores were reviewed. The primary endpoint was frequency of mictruition, with PVR, IPSS, Qmax as secondary endpoints. RESULTS: Baseline characteristics were similar between the treatment groups, although body mass index was higher in the placebo group (32.7 vs. 26.8, p⫽0.02, See Table 1). The median age was 67 years, with a median IPSS of 20, Qmax of 13.5mL/s, PVR of 49cc, and 12 voids/day. Patients receiving BoNT demonstrated higher Qmax compared to placebo (p⬍0.01, See Table 2) at the 90 days follow-up. Urinary frequency, IPSS, and PVR were unchanged postoperatively in both groups. CONCLUSIONS: Patients receiving BoNT showed a significantly higher Qmax than those receiving placebo. No significant changes in urinary frequency or symptom scores were seen however.

100% 0.99

0.62

0.33

Source of Funding: None

1972 THE ZURICH EXPERIENCES INCLUDING 10 YEAR RESULTS OF 253 CASES TREATED WITH BOTULINUM-A TOXIN INJECTIONS INTO THE DETRUSOR MUSCLE FOR OVERACTIVE BLADDER REFRACTORY TO ANTICHOLINERGICS Daniel Max Schmid*, Zurich, Switzerland; Sharmistha Roy-Guggenbuehl, Zollikerberg, Switzerland; Tullio Sulser, Zurich, Switzerland INTRODUCTION AND OBJECTIVES: Aim of this prospective study was to evaluate the efficacy and long-term results of low-dose (100 U) Botulinum-A toxin (BoNT-A) injections into the detrusor to treat patients suffering from severe non-neurogenic overactive bladder (OAB). METHODS: 253 patients (68 m, 185 f; mean age 57 y., 18-87 y.) were treated by injections of 100 U of BoNT-A. Micturition diary, urodynamics, and neurological status were performed before treatment. Clinical and urodynamic checks and quality of life assessment (QoL) were performed at baseline and 12 weeks after BoNT-A treatment. Follow-up included duration of effect, re-injection rate and intervals between treatments. RESULTS: Overall, 83 % of patients showed a significant (p⬍0.001) improvement of their bladder function in regard to symptoms as well as to urodynamic parameters: Urgency completely disappeared in 75% and incontinence in 85% within 2 weeks, whereas daily pad usage dropped from 5 to 0.5 pads/day. Frequency decreased from 16 to 7 micturitions and nocturia from 5 to 2.5 (-50%), respectively. MCC increased from mean 230 to 395 ml (⫹71%), BC rised from 20 to 44 ml/cmH2O. FDV increased from mean 120 to 215 ml.