One treatment with onabotulinumtoxinA relieves symptoms of overactive bladder in patients refractory to one or more oral medications.

INTRODUCTION AND HYPOTHESIS: Patients with overactive bladder (OAB) often undergo prolonged treatment with one or more oral OAB medications. OnabotulinumtoxinA (onabotA), a type A botulinum toxin, may provide an appropriate alternative to oral treatments in patients intolerant of or refractory to one or more oral OAB medications. The GRACE study demonstrated real-world benefits of onabotA treatment for OAB in patients refractory to oral medications. This exploratory post hoc analysis of data from the GRACE study aims to determine if treatment history impacts benefit from treatment with onabotA. METHODS: This is a subanalysis of the GRACE study, a prospective observational study (NCT02161159) that enrolled patients with symptomatic OAB inadequately managed by at least one oral OAB medication. Patients had a treatment history of one or more anticholinergics (AC) and/or ß-3 adrenoreceptor agonists (ß-3) for relief of OAB; results were stratified according to treatment history. Patients in this analysis elected to discontinue oral medications upon treatment with onabotA. Safety was followed for 12 months in all patients that received at least 1 dose of onabotA; efficacy was determined over a 12-week period. RESULTS: Compared to baseline levels, significant reductions in urinary incontinence (UI), urgency, micturition, and nocturia were noted as early as 1 week and were sustained at 12 weeks, regardless of the type and number of oral medications taken before treatment with onabotA. At 12 weeks post-onabotA, the mean change from baseline UI episodes/day for those with a treatment history of only one AC was -2.4 (n = 43, p ≤ 0.001); more than one AC, -2.4 (n = 52, p ≤ 0.001); one ß-3, -3.3 (n = 12, p < 0.05); at least one AC and at least one ß-3, -3.2 (n = 56, p ≤ 0.001). Pad and liner use was significantly decreased at 12 weeks post-onabotA across all treatment history groups. Reductions in diaper pant use varied, with less of a reduction in patients with a treatment history of more than one AC compared to patients with a history of at least one AC and one ß-3 (p < 0.05) or those with a history of only one AC (p < 0.05). Overall, a total of 253/288 of patients (88%) reported improvements on the treatment benefit scale 12 weeks after treatment with onabotA, regardless of type and number of prior oral medications. In the population of patients that received at least one dose of onabotA (N = 504), 57 adverse events were reported in 38 patients (7.5%); 9 were serious (1.8%). Urinary retention was reported in 5 patients (1.0%); 1 was severe (0.2%). Symptomatic urinary tract infection was reported in 2 patients (0.4%). CONCLUSIONS: In this exploratory post hoc analysis of real-world data from the GRACE study, there were few significant differences in outcomes based on the type and number of prior oral medications. Thus, patients who are refractory to one or more oral OAB medications may benefit from earlier treatment with onabotA.

OnabotulinumtoxinA is a well tolerated and effective treatment for refractory overactive bladder in real-world practice.

INTRODUCTION AND HYPOTHESIS: In randomized clinical trials onabotulinumtoxinA was demonstrated to be an effective and well-tolerated treatment for overactive bladder (OAB) with urinary incontinence (UI). However, data reporting onabotulinumtoxinA use in everyday clinical practice are limited. Here, we present the results from a large, first-of-its-kind real-world study in patients with OAB. METHODS: This was a prospective, observational, multinational study (GRACE; ClinicalTrials.gov , NCT02161159) performed in four European countries. Patients (N = 504) aged ≥ 18 years with OAB inadequately managed with ≥ 1 anticholinergic received onabotulinumtoxinA per their physician's normal clinical practice. RESULTS: Physicians primarily used rigid cystoscopes for onabotulinumtoxinA injection; anesthesia/analgesia was utilized during most treatment procedures. Significant reductions in UI episodes/day from baseline to weeks 1 and 12 were observed as well as in micturition, urgency, and nocturia episodes/day. These improvements in urinary symptoms corresponded to higher scores on the treatment benefit scale at week 12. The use of other OAB medications dropped from baseline to weeks 1 and 12 and was sustained to week 52, which paralleled a reduction in the number of incontinence products used during that time frame. Adverse reactions were reported in 2.6% of patients throughout the study. CONCLUSIONS: In this real-world study, significant improvements in urinary symptoms were seen following onabotulinumtoxinA treatment as early as week 1 and sustained to at least week 12. This was accompanied by a reduced reliance upon incontinence products and reduction in concomitant OAB medication use. OnabotulinumtoxinA was well tolerated with no new safety signals.

The Stockholm Spinal Cord Uro Study: Changing patterns of urological surgery in a regional prevalence group through 50 years - Outcomes and lessons learned.

AIMS: To examine the number and types of urological surgical procedures carried out in a regional prevalence population of patients with traumatic spinal cord injury (SCI) during five decades, evaluate objective and patient-reported outcomes and to consider lessons learned for further improvement of surgical treatment in this patient group. METHODS: In a cross-sectional study of 412 patients with traumatic SCI, one-third had undergone urological surgery through a period of up to 50 years. Data on types of surgery, complications, follow-up and outcomes were collected in a retrospective review of patient files. S-creatinine, S-cystatin-C, renal ultrasound and a questionnaire regarding complications during the preceding year were assembled as part of a yearly follow-up. Descriptive statistics were calculated. Logistic regression was used to determine risk profiles for the incidence of urological surgery. RESULTS: A total of 137 patients had undergone 262 urological surgical interventions. The incidence was highest amongst persons with a cervical-thoracic neurological level of spinal cord lesion and during the first 2 years after SCI. Surgery for urinary stones constituted 29% of all procedures. One-fourth of the patients had undergone 47% of all procedures, notably urinary diversion and ensuing complications, implants and revisions, repeated stone interventions or bladder outlet procedures. After reconstructive surgery functional outcomes and patient-reported satisfaction were generally favourable, but long-term signs of renal complications were frequent. CONCLUSIONS: Urological surgery after SCI involves imperative as well as reconstructive procedures, some of which are challenging and call for centralisation to devoted teams. Prospective studies of reconstructive urology are warranted, including more extensive patient-reported outcomes.

The Stockholm Spinal Cord Uro Study: 3. Urodynamic characteristics in a regional prevalence group of persons with spinal cord injury and indications for improved follow-up.

AIMS: Examine the outcome of urodynamic studies in a regional prevalence group of patients with traumatic spinal cord injury (SCI), explore relationships between urodynamic parameters and renal complications/other SCI-related dysfunctions, assess the role of urodynamics in SCI follow-up. METHODS: In a cross-sectional study, 211 patients were included, who attended a yearly check-up and had urodynamics performed as part of the follow-up in addition to S-creatinine, S-cystatin-C, renal ultrasound, and a questionnaire regarding complications. Relationships between urodynamic parameters and renal complications/other SCI-related dysfunctions were explored by descriptive and comparative statistics. RESULTS: Neurogenic detrusor overactivity (NDO) was found in 150, underactive/acontractile detrusor in 44, normal detrusor function in 17 patients. Maximum detrusor pressures during filling/voiding in NDO attained mean levels of >40 cm H2O in 68% of patients and >25 cm H2O in 83%. Reduced compliance of the bladder wall, cystometric bladder capacity <250 mL, and detrusor overactivity leakage during filling were associated with higher detrusor pressures. Detrusor overactivity during more than one-third of the filling phase was significantly related to signs of renal complications among patients with SCI duration 11-20 years. No significant relationships were found between other urodynamic parameters and renal/other SCI-related complications. Renal complications in underactive/acontractile and normal detrusor function co-varied with evidence of previous NDO and other co-morbidities which may negatively influence kidney function. CONCLUSIONS: Maximum detrusor pressures during the filling/voiding phases attained high levels in a majority of patients. Detrusor overactivity during more than one-third of the filling phase was significantly related to signs of renal complications.

The Stockholm Spinal Cord Uro Study: 2. Urinary tract infections in a regional prevalence group: frequency, symptoms and treatment strategies.

Objective: To examine symptomatic urinary tract infections (UTI) in a regional prevalence group of patients with traumatic spinal cord injury (SCI), to assess risk factors for recurring infections and to identify a high-risk sub-population for frequently recurring and severe febrile UTIs.Materials and Methods: Four hundred and twelve patients who attended a yearly check-up at the Spinalis SCI clinic were included. A regional programme for neurogenic bladder dysfunction was applied, including S-creatinine and S-cystatin-C, urine culture, residual urine, ultrasound of kidneys, urodynamic studies and a questionnaire regarding complications during the preceding year. Descriptive statistics and regression analysis were used to estimate risk factors.Results: Nearly half of all patients reported ≥1 UTI during the preceding year with a mean number of 3.6. Persons who use normal voiding had the lowest frequency, while those with catheter-assisted voiding reported the highest numbers. A sub-group of patients had more frequent and severe UTIs. They were characterized by a cervical or thoracic neurological level lesion and a more severe injury and the presence of SCI-related complications such as spasticity, neuropathic pain and autonomic dysreflexia. The most common signs and symptoms of UTI were smelly and cloudy urine, feelings of malaise and increased spasticity.Conclusions: Risk profiles for recurring and severe UTIs were catheter-assisted voiding, cervical or thoracic levels and more complete neurological lesions and the co-existence of other SCI-related complications. There is a need for an increased understanding of the special symptoms of UTI in this patient group and a strategy to avoid unspecific antibiotic treatment.

The Stockholm Spinal Cord Uro Study: 1. Basic characteristics and problem inventory.

Objective: To assess urinary tract function and complications in a regional prevalence group of patients with traumatic spinal cord injury (SCI), and to estimate risk factors for recurring complications.Materials and methods: A total of 412 patients who attended a yearly check-up at the Spinalis SCI clinic were included. A regional follow-up programme for neurogenic bladder dysfunction was applied, including S-creatinine and S-cystatin-C, urine culture, residual urine, ultrasound of kidneys, urodynamic studies, and a questionnaire regarding complications during the preceding year. Descriptive statistics and logistic regression were used to estimate risk factors.Results: All patients completed blood tests and the questionnaire. A urine culture was completed by 96%, ultrasound by 88%, residual urine by 75%, urodynamics by 51%, and all parts of the study by 47%. One quarter of patients displayed pathological findings regarding kidney function. Urodynamics verified neurogenic overactive bladder in a majority, and a high proportion with intravesical filling pressures above 40 cm H2O, a commonly used cut-off level for kidney safety. Subjectively, 47% of patients reported complications during the past year with urinary tract infection (UTI) as the most common one. Other complications were rare.Conclusions: With the aid of a regular follow-up programme, SCI patients can achieve a relatively stable situation regarding urinary tract function. UTI is the most common complication. Indicators of renal complications are frequent but not clearly related to the number of UTIs, nor to intravesical filling pressures. Main risk factors for complications are cervical levels and more complete neurological lesions.

Efficacy and impact of botulinum toxin A on quality of life in patients with neurogenic detrusor overactivity: a randomised, placebo-controlled, double-blind study.

OBJECTIVE: To evaluate the effect of a single injection of 500 U of botulinum toxin A (BTX-A; Dysport) on use of oral rescue medication, bladder compliance, continence and quality of life in a randomized, placebo-controlled, double-blind study in patients with incontinence due to neurogenic detrusor overactivity. As this group of patients often have severe symptoms, oral tolterodine was allowed as rescue medication and the amount of tolterodine consumed was our primary endpoint. MATERIAL AND METHODS: A total of 31 patients with urinary leakage due to spinal cord injury, myelomeningocele, trauma at birth, multiple sclerosis and myelitis of another cause were randomized to intravesical injections of either 500 U of BTX-A or placebo. Intake of tolterodine and episodes of urinary leakage were registered. Cystometry was performed after 6, 12 and 26 weeks and quality of life was assessed. RESULTS: Patients in the BTX-A group had a significantly lower intake of tolterodine throughout the study compared to those in the placebo group (p=0.003). Cystometric capacity was significantly higher at 6 (p<0.001) and 12 weeks (p=0.026) and maximum detrusor pressure and frequency of urinary leakage were significantly (p<0.01) lower during follow-up in the BTX-A group compared to the placebo group. In addition, many quality-of-life parameters were significantly improved in the BTX-A group compared to the placebo group. CONCLUSIONS: Intravesical injection of 500 U of BTX-A in patients with neurogenic detrusor instability was shown to be an effective treatment which reduced use of oral medication, high detrusor pressure and frequency of urinary leakage during the overall study period of 26 weeks. Quality of life was also significantly improved.

Treatment of stress urinary incontinence using a copolymer system: impact on quality of life.

OBJECTIVE: To investigate the effect on quality of life (QoL) of a novel system for treatment of stress urinary incontinence (SUI). PATIENTS AND METHODS: In an open, prospective, multicentre study, 42 women not previously treated by invasive therapy and with urodynamically verified SUI received 4 x 1.0 mL or 4 x 0.7 mL of non-animal stabilized hyaluronic acid/dextranomer copolymer injected transurethrally into the urethra via the Implacer device (Zuidex system, Q-Med AB, Uppsala, Sweden). QoL was assessed using the King's Health Questionnaire. The patients' perception of treatment benefit and the number of incontinence episodes/24 h were also investigated. RESULTS: There were significant improvements over baseline in seven of 10 domains of the King's Health Questionnaire at 3 months, and these improvements were sustained at 1 year. For the change from baseline to 1 year, eight of 10 domains showed a significant positive correlation with the number of incontinence episodes/24 h. In terms of treatment benefit, most of the women perceived an improvement at 1, 3, 6 and 12 months. Of the 18 women requiring re-treatment, most perceived an improvement at 3, 6 and 12 months. CONCLUSION: Treatment with the Zuidex system produced significant improvements over a year in both subjective QoL and objective incontinence measures, with a significant positive correlation between them.

Efficacy and safety of a novel system (NASHA/Dx copolymer using the Implacer device) for treatment of stress urinary incontinence.

OBJECTIVES: To investigate the efficacy and safety of non-animal-stabilized hyaluronic acid/dextranomer (NASHA/Dx) copolymer for transurethral injection using a new guiding instrument (the Implacer) for stress urinary incontinence. METHODS: In an open, prospective, multicenter study, 42 invasive therapy-naive female patients with stress urinary incontinence were given 4 x 1.0 mL or 4 x 0.7 mL of NASHA/Dx copolymer using the Implacer. The efficacy parameters, measured at baseline and 1, 3, 6, and 12 months after treatment, included cough-induced leak point pressure, urine leakage by provocation test, number of incontinence episodes in 24 hours, and patient perception of bladder condition, rated on a 6-point scale. RESULTS: The collected cough-induced leak point pressure data were not judged to be valid and reliable. Statistically significant reductions in median urine leakage were observed (P <0.0001), from 36 g (range 0.0-300) after 20 "jumping jacks" or vigorous coughs at baseline to 5.5 g (range 0.0-98) at 3 months and sustained at 12 months (7.0 g, range 0.0-98). Of the 42 patients, 32 (76%) demonstrated a degree of improvement in urine leakage at 3 and 12 months. The median number of incontinence episodes in 24 hours decreased significantly from 1.9 (range 0.0-24) at baseline to 0.4 (range 0.0-24) at 12 months (P <0.0001). At both 3 and 12 months, 29 patients (69%) had improved by at least one category on the 6-point patient perception scale. Treatment was well tolerated, and no complications were reported with use of the Implacer. CONCLUSIONS: The results of this study indicate that a novel system (NASHA/Dx copolymer insertion using the Implacer) is an effective and well-tolerated treatment for invasive therapy-naive patients with stress urinary incontinence, with improvement sustained for at least 12 months. These encouraging results warrant additional study.

Treatment of stress urinary incontinence: recent developments in the role of urethral injection.

Stress urinary incontinence is prevalent in adult women and has a considerable impact on quality of life. However, it often remains undiagnosed and therefore untreated. Non-invasive treatment is likely to be offered in mild cases and may entail physiotherapy, minimally invasive devices or pharmacotherapy. Surgical intervention is widely considered as the only effective option for more severe cases. These strategies are not suitable for all patients, and urethral injection represents an alternative, minimally invasive procedure. The choice of the bulking agent is the key to the success of this treatment: the most extensively studied are silicone, polytetrafluoroethylene and bovine collagen. However, doubts regarding the safety and efficacy of these materials has led to the development of carbon-coated zirconium beads, calcium hydroxylapatite and dextranomer/hyaluronic acid (Dx/HA) copolymer. Of these, the most clinical experience has been gained with Dx/HA copolymer. Until 2 years ago, urethral injection could only be administered endoscopically. The recent development of devices for 'blind' injection has increased the speed and convenience of urethral injection, removing the need for surgical facilities. Although few data are yet available, it is conceivable that urethral injection administered 'blind' may in future be considered as an option for all patients failing non-invasive treatment.