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Editorial: Mirabegron the first β3-adrenoceptor agonist for OAB: a summary of the phase III studies

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The study reported in this edition of BJUI details the results of a large phase III study conducted in Japan contrasting 50 mg mirabegron, the new β3-adrenoceptor agonist, to placebo with tolterodine as an active comparator [1]. This adds to the body of knowledge already provided by phase III evaluations reported from Europe [2], where tolterodine was also used as an active comparator and North America [3], where the efficacy of 25–100 mg was compared with placebo [4]. As the first in this new class of compounds with a mechanism of action that is distinct from that of the antimuscarinic agents, which are the mainstay of overactive bladder (OAB) therapy to date, there is clearly interest in the efficacy and in particular the safety of this new class of compound. This has been evaluated in a long-term safety study [5].

This paper [1] confirms the findings evident in these other publications, which suggest a favourable short- and long-term tolerability profile for mirabegron in patients with OAB. In particular, excluding typical anticholinergic side-effects, such as dry mouth, which occurred with a similar incidence with mirabegron as placebo, but was reported in 13.3% of tolterodine patients, there was no evidence of any cardiotoxicity with mirabegron, which is consistent with a previous pooled analysis of the European and North American studies [6]. In this pooled analysis, mirabegron was associated with mean increases of 0.4–0.6 mmHg in blood pressure and ≈1 beat/min in heart rate, both reversible upon treatment discontinuation. In the long-term study, the changes in heart rate seen with mirabegron 50 mg were less than those seen with tolterodine. Changes in vital signs did not result in more cardiovascular-related adverse events in patients treated with mirabegron compared with those treated with placebo or tolterodine in both the pooled 12-week and the 1-year long-term studies. In addition, there was one case of urinary retention with mirabegron in the pooled 12-week studies; the incidence being less than placebo or tolterodine. Clearly from the evidence now available, mirabegron has an efficacy similar to that seen with tolterodine and significantly better than placebo for most of the symptoms of the OAB symptom complex. In conclusion, mirabegron is well-tolerated and as efficacious as anticholinergic therapy. Further analyses of the phase III data has shown that mirabegron is effective in both naïve patients and those that have failed to either tolerate or respond to a previous anticholinergic therapy [7].

Future work should include an adequately powered direct comparison to antimuscarinic therapy. Furthermore, data on the combination of mirabegron and an antimuscarinic have already shown potential benefit in a phase II study, and this should be explored further [8]. Other interesting areas to explore will be the use of this therapy in both male patients and patients with neurogenic bladder dysfunction.

Read the full article
Christopher Chapple
Department of Urology, The Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, UK

 

References

  1. Yamaguchi O, Marui E, Kakizaki H et al. Phase III, randmised, double-blind, placebo-controlled study of the β3 -adrenoceptor agonist mirabegron, 50 mg once daily, in Japanese patients with overactive bladder. BJU Int 2014; 113: 951–960.
  2. Khullar V, Amarenco G, Angulo JC et al. Efficacy and tolerability of mirabegron, a β(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol 2013; 63: 283–295
  3. Nitti VW, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol 2013; 189: 1388–1395
  4. Herschorn S, Barkin J, Castro-Diaz D et al. A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder. Urology 2013; 82: 313–320
  5. Chapple CR, Kaplan SA, Mitcheson D et al. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a β(3)-adrenoceptor agonist, in overactive bladder. Eur Urol 2013; 63: 296–305
  6. Nitti VW, Khullar V, van Kerrebroeck P et al. Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. Int J Clin Pract 2013; 67: 619–632
  7. Khullar V, Cambronero J, Angulo JC et al. Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial. BMC Urol 2013; 13: 45
  8. Abrams P, Kelleher C, Staskin D et al. Combination treatment with mirabegron and solifenacin in patients with overactive bladder: efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (symphony). Eur Urol 2014. doi: 10.1016/j.eururo.2014.02.012

 

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Article of the week: Both men and women with OAB find better relief with fesoterodine

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video by Dr. Ginsberg and colleagues.

If you only have time to read one article this week, it should be this one.

Efficacy of fesoterodine compared with extended-release tolterodine in men and women with overactive bladder

David Ginsberg, Tim Schneider*, Con Kelleher†, Philip Van Kerrebroeck‡, Steven Swift§, Dana Creanga and Diane L. Martire**

Department of Urology, University of Southern California, Los Angeles, CA, §Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, Consultant to Pfizer Inc, **Pfizer Inc, New York, NY, USA, *Praxisklinik Urologie Rhein/Ruhr, Mülheim, Germany, †St. Thomas’ Hospital, London, UK, and ‡Department of Urology, Maastricht University Medical Center, Maastricht, The Netherlands

Read the full article
OBJECTIVE

• To assess the efficacy of fesoterodine 8 mg vs extended-release (ER) tolterodine 4 mg for overactive bladder (OAB) symptoms in terms of patient-reported outcomes in women and in men.

SUBJECTS AND METHODS

•  Pooled data from two 12-week, randomized, double-blind, double-dummy studies were analysed.

• Participants eligible for the studies were ≥18 years old, had self-reported OAB symptoms for ≥3 months in 3-day baseline diaries and had ≥8 micturitions and ≥1 urgency urinary incontinence (UUI) episode per 24 h.

• Individuals were randomized to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks), ER tolterodine (4 mg), or placebo.

• Changes from baseline in 3-day bladder diary variables and scores from the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q), were assessed, as was the ‘diary-dry’ rate (the proportion of subjects with >0 UUI episodes according to baseline diary and no UUI episodes according to post-baseline diary).

• The primary endpoint was the change from baseline to week 12 in UUI episodes.

RESULTS

• At week 12, women showed significantly greater improvement with fesoterodine 8 mg (n = 1374) than with ER tolterodine 4 mg (n= 1382) and placebo (n = 679) in UUI episodes (primary endpoint), micturition frequency, urgency episodes, and all other diary endpoints (except nocturnal micturitions versus ER tolterodine), and also in scores on the PPBC, UPS, and all OAB-q scales and domains (all P < 0.005).

• Diary-dry rates in women were significantly greater with fesoterodine (63%) than with tolterodine (57%; P = 0.002) or placebo (48%; P < 0.0001).

• In men, there were no significant differences in improvement in UUI episodes between any treatment groups at week 12. Improvements in men were significantly greater with fesoterodine 8 mg (n = 265) than with ER tolterodine (n = 275) for severe urgency and the OAB-q Symptom Bother domain and were also significantly greater with fesoterodine than with placebo (n = 133) for micturition frequency, urgency episodes, severe urgency episodes, PPBC responses and scores on all OAB-q scales and domains at week 12 (all P < 0.04).

• The most frequently reported treatment-emergent adverse events in both genders were dry mouth (women: fesoterodine, 29%; ER tolterodine, 15%; placebo, 6%; men: fesoterodine, 21%; ER tolterodine, 13%; placebo, 5%) and constipation (women: fesoterodine, 5%; ER tolterodine, 4%; placebo, 2%; men: fesoterodine, 5%; ER tolterodine, 3%; placebo, 1%).

• Urinary retention rates were low in women (fesoterodine, <1%; ER tolterodine, <1%; placebo, 0%) and men (fesoterodine, 2%; ER tolterodine <1%; placebo, 2%).

CONCLUSION

• This analysis supports the superiority of fesoterodine 8 mg over ER tolterodine 4 mg on diary endpoints, including UUI, symptom bother and health-related quality of life in women.

• In men, fesoterodine 8 mg was superior to ER tolterodine 4 mg for improving severe urgency and symptom bother.

 

Read Previous Articles of the Week

 

Editorial: Fesoterodine is superior to extended-release tolterodine for OAB

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The treatment of overactive bladder (OAB) is still based on antimuscarinics, although the recent introduction of β3 agonists and botulinum toxin A has opened a window of new opportunities, the range of which is yet to be defined.

The clinical development of fesoterodine has taken the Urological community by surprise and raised levels of expectation. From a pharmacological standpoint fesoterodine is just a ‘smart drug’ because it is the pro-drug of 5-hydroxymethyl tolterodine (5-HMT) the active metabolite of tolterodine that is metabolised into 5-HMT by cytochrome P450 (CYP) enzymes, the activity of which is known to suffer significant genetic variability. Fesoterodine is transformed into 5-HMT by nonspecific esterase pathways. Pharmacokinetic studies of fesoterodine have shown highly predictable plasma levels of the 5-HMT after fesoterodine administration. Whether or not the better bioavailability offered by the esterase-related activation pathway translates into a larger clinic benefit for our patients with OAB was initially unclear. A phase II study showed a good safety profile and suggested that two different doses of fesoterodine could be proposed with a good balance between efficacy and adverse events. Results of the pivotal phase III study confirmed how the two different doses: 4 and 8 mg, tended to separate with a larger benefit observed with the larger dose, although a slightly larger incidence of adverse events was observed. As long as the comparison between 4 and 8 mg of fesoterodine was not part of the pre-planned analysis, the results of thepost hoc analysis had to be confirmed in a properly design prospective randomised trial.

The assumption that a higher drug dose brings a larger therapeutic effect is very often just wishful thinking and clinical pharmacology has often disproved such a belief. What is instead clear, from the paper of David Ginsberg et al., which pools data from two randomised trials (BJU Int 2010, BJU Int 2011), is that the flexible dosage available with fesoterodine brings a clinically relevant advantage in our daily practice.

The question is whether there is a real need for dose flexibility in the management of OAB. After a couple of decades in this area, I strongly believe that flexible dosing is crucial, in general, and even more so in functional urology. This is in fact an area where storage and voiding function needs to be rebalanced; a too weak or too strong effect may easily lead to a therapeutic failure. Reaching the right balance between therapeutic effect and adverse events is crucial while using antimuscarinics. If 40% of patients who withdraw from anticholinergic medications do so because of insufficient benefit, another large proportion (22%) discontinues treatment because of side-effects.

The question in real-life practice, provided treatment should be initiated with a 4 mg dose because of regulatory issues, is whether the dose should be upgraded and when, should this be left to the individual patient’s decision or should it be guided by the treating physician? There is no ‘golden’ rule and in my opinion is a matter of patient expectations. Most patients expect drugs to cure the conditions they are prescribed for, although we know this is rarely the case. When patients are properly informed about the effect of antimuscarinics treatment they will often choose their goal, some patients will look for reducing OAB symptoms while avoiding dry mouth and constipation as much as possible, others will want to become dry and accept higher levels of adverse events. Furthermore, because of body distribution, different doses of drugs may be required in a 45 kg lady and in a 90 kg man, although this may depend on the drug bioavailability at the target organ. The same applies to patients with normal detrusor contractility and patients with a weak bladder, such as patients with multiple sclerosis. The ‘one dose fits all’ approach does not seem to be the way to go.

The larger therapeutic effect achieved in the 8 mg fesoterodine group is obtained at the expense of almost doubling the incidence of dry mouth (from 15% to 28%), although the increase in the constipation rate is just 1%. Whether or not the observed differential improvement between tolterodine 4 mg and fesoterodine 8 mg is clinically relevant is matter for discussion for the investigators but looking at the parallel improvement in all patients reported outcomes, the difference seems to be of importance from the patient perspective.

The therapeutic area of storage disorders, e.g. OAB, is experiencing a number of paradigm changes, including the availability of flexible dosing of antimuscarinics, β3 agonists and botulinum toxin A. What once used to be a neglected area of functional urology is now an exciting area of basic and clinical research.

Andrea Tubaro and Cosimo De Nunzio*
Urology Unit, Department of Clinical and Molecular Medicine, Faculty of Health Sciences, Sapienza University, and *Urology Unit, Sant’Andrea Hospital, Rome, Italy

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Video: Fesoterodine vs tolterodine in men and women with OAB

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Efficacy of fesoterodine compared with extended-release tolterodine in men and women with overactive bladder

David Ginsberg, Tim Schneider*, Con Kelleher†, Philip Van Kerrebroeck‡, Steven Swift§, Dana Creanga and Diane L. Martire**

Department of Urology, University of Southern California, Los Angeles, CA, §Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, Consultant to Pfizer Inc, **Pfizer Inc, New York, NY, USA, *Praxisklinik Urologie Rhein/Ruhr, Mülheim, Germany, †St. Thomas’ Hospital, London, UK, and ‡Department of Urology, Maastricht University Medical Center, Maastricht, The Netherlands

Read the full article
OBJECTIVE

• To assess the efficacy of fesoterodine 8 mg vs extended-release (ER) tolterodine 4 mg for overactive bladder (OAB) symptoms in terms of patient-reported outcomes in women and in men.

SUBJECTS AND METHODS

•  Pooled data from two 12-week, randomized, double-blind, double-dummy studies were analysed.

• Participants eligible for the studies were ≥18 years old, had self-reported OAB symptoms for ≥3 months in 3-day baseline diaries and had ≥8 micturitions and ≥1 urgency urinary incontinence (UUI) episode per 24 h.

• Individuals were randomized to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks), ER tolterodine (4 mg), or placebo.

• Changes from baseline in 3-day bladder diary variables and scores from the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q), were assessed, as was the ‘diary-dry’ rate (the proportion of subjects with >0 UUI episodes according to baseline diary and no UUI episodes according to post-baseline diary).

• The primary endpoint was the change from baseline to week 12 in UUI episodes.

RESULTS

• At week 12, women showed significantly greater improvement with fesoterodine 8 mg (n = 1374) than with ER tolterodine 4 mg (n= 1382) and placebo (n = 679) in UUI episodes (primary endpoint), micturition frequency, urgency episodes, and all other diary endpoints (except nocturnal micturitions versus ER tolterodine), and also in scores on the PPBC, UPS, and all OAB-q scales and domains (all P < 0.005).

• Diary-dry rates in women were significantly greater with fesoterodine (63%) than with tolterodine (57%; P = 0.002) or placebo (48%; P < 0.0001).

• In men, there were no significant differences in improvement in UUI episodes between any treatment groups at week 12. Improvements in men were significantly greater with fesoterodine 8 mg (n = 265) than with ER tolterodine (n = 275) for severe urgency and the OAB-q Symptom Bother domain and were also significantly greater with fesoterodine than with placebo (n = 133) for micturition frequency, urgency episodes, severe urgency episodes, PPBC responses and scores on all OAB-q scales and domains at week 12 (all P < 0.04).

• The most frequently reported treatment-emergent adverse events in both genders were dry mouth (women: fesoterodine, 29%; ER tolterodine, 15%; placebo, 6%; men: fesoterodine, 21%; ER tolterodine, 13%; placebo, 5%) and constipation (women: fesoterodine, 5%; ER tolterodine, 4%; placebo, 2%; men: fesoterodine, 5%; ER tolterodine, 3%; placebo, 1%).

• Urinary retention rates were low in women (fesoterodine, <1%; ER tolterodine, <1%; placebo, 0%) and men (fesoterodine, 2%; ER tolterodine <1%; placebo, 2%).

CONCLUSION

• This analysis supports the superiority of fesoterodine 8 mg over ER tolterodine 4 mg on diary endpoints, including UUI, symptom bother and health-related quality of life in women.

• In men, fesoterodine 8 mg was superior to ER tolterodine 4 mg for improving severe urgency and symptom bother.

Article of the week: Botulinum toxins are not interchangeable for overactive bladder

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Miss Ravindra and colleagues discussing their article.

If you only have time to read one article this week, it should be this one.

Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox®) or abobotulinumtoxinA (Dysport®) make a difference?

Pravisha Ravindra, Benjamin L. Jackson and Richard J. Parkinson

Nottingham Urology Centre, Nottingham University Hospitals, NHS Trust, Nottingham, UK

Read the full article
OBJECTIVE

• To compare the clinical effects of two different commercially available botulinum toxin type A products, onabotulinumtoxinA (Botox®; Allergan Inc., Irvine, CA, USA) and abobotulinumtoxinA (Dysport®; Ipsen Ltd, Slough, UK), on non-neurogenic overactive bladder (OAB).

PATIENTS AND METHODS

• We included 207 patients, who underwent treatment with botulinum toxin type A for non-neurogenic OAB from January 2009 to June 2012 at our institution, in a prospective database that recorded details of their presentation, treatment and outcomes.

• In December 2009, our institution switched from using onabotulinumtoxinA to using abobotulinumtoxinA.

RESULTS

• Results from the onabotulinumtoxinA cohort (n = 101) and the abobotulinumtoxinA cohort (n = 106) were compared.

• Similar reductions in daytime frequency, nocturia and incontinence episodes were observed after treatment, with no difference in duration of effect.

• The abobotulinumtoxinA cohort had almost twice the rate of symptomatic urinary retention (23 vs 42%) requiring intermittent self-catheterisation (ISC).

CONCLUSIONS

• AbobotulinumtoxinA use was complicated by a significantly higher risk of requiring ISC.

• The study suggests that these two toxins are not interchangeable at the doses used.

 

Read Previous Articles of the Week

 

Editorial: Botulinum toxin-A for overactive bladder: formulations, dosing and clean intermittent catheterisation

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The article by Ravindra et al., in this issue of the BJUI, tries to address an important question of comparing the 2 commonest types of botulinum toxin-A (BTX-A), Ona- and AbobotulinumtoxinA. In their institution they changed from OnbotulinumtoxinA to AbobotulinumtoxinA and thus compared results of their different case series for patients with overactive bladder syndrome. Very few studies have tried to address this issue for botulinum toxin-A use in the urinary tract and to my knowledge there are no head to head studies. The authors found the 2 types of BTX-A equivalent in terms of voiding diary parameters, ICIQ questionnaires, patient reported global satisfaction and duration of effect but noted a significant difference for clean intermittent self catheterisation (CISC) rates (23% OnabotulinutoxinA vs 42% AbobotulinumtoxinA). The dose used for OnabotuliumtoxinA was 200 IU and for AbobotulinumtoxinA was 500 IU initially and then later 300 IU. One must bear in mind some important considerations which limit the impact of the result. Namely the non-randomised, retrospective nature of the study and the fact that the study was not designed or powered to assess the BTX-A formulations in this way. The primary endpoint in this case was a patient reported satisfaction measure indicating that 85% had ‘better’ or ‘much better’ symptoms which I think is a fair reflection in my experience. Furthermore there were significant gaps in data acquisition particularly for voiding diary, PVR and ICIQ data which again is not that uncommon in retrospective studies. No urodynamic data was included which I think may also have been interesting to look at when assessing outcomes and CISC rates.

None the less the study generates some interesting discussion about the formulations, optimal dosing and the dosing equivalence. The study is one of the first to report on the use of AbobotulinumtoxinA at 300 IU as most studies utilised 500 IU. In view of the move to lower doses of OnabotulinumtoxinA to treat refractory OAB of 100–150 IU, this dose seems appropriate. Evidence from a large dose ranging RCT using OnabotulinumtoxinA suggests no further efficacy beyond doses of 150 IU but an increase in voiding dysfunction. Interestingly CISC rates are still high at 300 IU in this study. A recent systematic review tried to assess the 2 formulations in aspects of BTX-A use for various lower urinary tract dysfunction. Due to the heterogenousity of the studies, a lack of standardised or high quality data a direct comparison between the 2 was not formally possible. It was noted that OnabotulinumtoxinA has been studied more extensively compared to AbobotulinumtoxinA and with both formulations CISC rates could be high at the doses used in this study (OnabotulinumtoxinA 43%; AbobotulinumtoxinA 35%). Assessing the compound muscle action potential of the extensor digitorum brevis muscle in healthy volunteers has suggested an AbobotulinumtoxinA to OnabotulinumtoxinA ratio of 1.57:1 (95% confidence interval: 0.77–3.20 units) with the data indicating that a dose-equivalence ratio of 3:1 was just within statistical error limits but ratios over 3:1 were too high. The same author following a review of the literature in treatments outside the urinary tract suggest a ratio of 2–2.5:1 maybe the most appropriate. An animal model of spinal cord injury and neurogenic detrusor overactivity to compare the 2 formulations has recently been published. The minimal effective dose of Abo- and OnabotulinumtoxinA was found to be 10 IU and 7.5 IU, respectively, for significant changes in cystometry.

When should CISC be instigated? Practice seems to vary considerably and thus results difficult to compare. Many clinicians will base CISC decisions on a cut off, typically 100–200 mL or on whether patients are symptomatic with their PVR. Chapple has suggested >40% of the functional capacity as a significant PVR and this to me seems entirely logical. Future studies should consider this as an endpoint regarding CISC.

At present, the decision as to which formulation is used in clinical practice is often based on local pharmacy regulation and financial considerations. Licensing is undoubtedly going to have a significant influence on this practice. OnabotulinumtoxinA is now licensed for use in many parts of the world to treat neurogenic detrsuor overactivity and has recently been approved by the FDA in the USA to treat refractory OAB. At the time of writing this editorial, no formulation is currently approved for refractory OAB in the UK.

Arun Sahai
Consultant Urologist & Honorary Senior Lecturer, Department of Urology, Guy’s Hospital MRC Centre for Transplantation, King’s College London, King’s Health Partners

Read the full article

Video: botox course the preferred choice for non-neurogenic OAB

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Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox®) or abobotulinumtoxinA (Dysport®) make a difference?

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Pravisha Ravindra, Benjamin L. Jackson and Richard J. Parkinson

Nottingham Urology Centre, Nottingham University Hospitals, NHS Trust, Nottingham, UK

Read the full article
OBJECTIVE

• To compare the clinical effects of two different commercially available botulinum toxin type A products, onabotulinumtoxinA (Botox®; Allergan Inc., Irvine, CA, USA) and abobotulinumtoxinA (Dysport®; Ipsen Ltd, Slough, UK), on non-neurogenic overactive bladder (OAB).

PATIENTS AND METHODS

• We included 207 patients, who underwent treatment with botulinum toxin type A for non-neurogenic OAB from January 2009 to June 2012 at our institution, in a prospective database that recorded details of their presentation, treatment and outcomes.

• In December 2009, our institution switched from using onabotulinumtoxinA to using abobotulinumtoxinA.

RESULTS

• Results from the onabotulinumtoxinA cohort (n = 101) and the abobotulinumtoxinA cohort (n = 106) were compared.

• Similar reductions in daytime frequency, nocturia and incontinence episodes were observed after treatment, with no difference in duration of effect.

• The abobotulinumtoxinA cohort had almost twice the rate of symptomatic urinary retention (23 vs 42%) requiring intermittent self-catheterisation (ISC).

CONCLUSIONS

• AbobotulinumtoxinA use was complicated by a significantly higher risk of requiring ISC.

• The study suggests that these two toxins are not interchangeable at the doses used.

Article of the week: Bladder and bowel: the link between OAB and IBS

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one

Relationship between overactive bladder and irritable bowel syndrome: a large-scale internet survey in Japan using the overactive bladder symptom score and Rome III criteria

Seiji Matsumoto, Kazumi Hashizume, Naoki Wada, Jyunichi Hori, Gaku Tamaki, Masafumi Kita, Tatsuya Iwata and Hidehiro Kakizaki

Asahikawa Medical University, Renal and Urological Surgery, Asahikawa, Hokkaidou, Japan

Read the full article
OBJECTIVE

• To investigate the association between overactive bladder (OAB) and irritable bowel syndrome (IBS) by using an internet-based survey in Japan.

SUBJECTS AND METHODS

• Questionnaires were sent via the internet to Japanese adults.

• The overactive bladder symptom score was used for screening OAB, and the Japanese version of the Rome III criteria for the diagnosis of IBS was used for screening this syndrome.

RESULTS

• The overall prevalence of OAB and IBS was 9.3% and 21.2%, respectively.

• Among the subjects with OAB, 33.3% had concurrent IBS.

• The prevalence of OAB among men was 9.7% and among women it was 8.9%, while 18.6% of men and 23.9% of women had IBS.

• Concurrent IBS was noted in 32.0% of men and 34.8% of women with OAB.

CONCLUSION

• Taking into account a high rate of concurrent IBS in patients with OAB, it seems to be important for physicians to assess the defaecation habits of patients when diagnosing and treating OAB.

In cases of early detection seek ibs treatment right away.

Read Previous Articles of the Week

Editorial: Think irritable bowel syndrome when treating overactive bladder

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The bladder and bowel are functionally related organs; they lie in close proximity, have similar innervations and some structural similarities, albeit having different functional characteristics; they are both critical for the storage, collection and expulsion of waste products. Several previous clinical reports have suggested that LUTS, such as overactive bladder syndrome (OAB), can occur concurrently with disorders of the colon, such as irritable bowel syndrome (IBS).

In the study entitled ‘Relationship between overactive bladder and irritable bowel syndrome: a large-scale internet survey in Japan using the overactive bladder symptom score and Rome III criteria’, Matsumoto et al. investigate the prevalence of OAB and IBS in Japan using a large scale internet based survey. In all, 10 000 randomly selected participants completed the surveys with equal numbers of men and women. Subjects were grouped according to age and gender and the prevalence and severity of OAB was assessed using the OAB symptom score (OABSS). The OABSS as an assessment tool combines OAB symptoms into a single score. Four main criteria were examined (daytime frequency, night-time frequency, urgency and urgency incontinence) and disease severity was assessed by overall score value (5, mild; 6–11, moderate; and >12 severe). Similar epidemiological studies have been conducted in the past; however, this is the first study to use the OABSS to assess OAB in a general population. IBS was assessed using the IBS module of the ROME III criteria.

The study found that in the population studied, the overall prevalence of OAB was 9.3% (with 9.7% of men and 8.9% of women affected) and increased with advancing age. Of those affected, 59% reported mild symptoms, 40% reported moderate symptoms and 1% reported sever symptoms. The prevalence of IBS was greater, with 21.2%  of people reporting symptoms (18.6% of men and 23.9% of women); however, conversely the incidence of IBS was reduced with age. Consistent with previous epidemiological studies conducted in Europe and the USA, 33.3% of participants reporting OAB symptoms also had concurrent IBS (32.0% men and 34.8% women), interestingly though, the prevalence of concurrent IBS and OAB was unaffected by age, suggesting that age is not a contributing factor to this relationship.

The exact aetiology of OAB and IBS, by virtue of the non-specific nature of both symptom syndromes, cannot be clearly defined. However, both disorders are characterised by at least increased frequency of visceral emptying due to increased sensation and in many cases motor hyperactivity. In the LUT this takes the form of urgency with associated detrusor overactivity in 40–90% of patients and in the bowel it manifests as pain and discomfort. Experimental studies in rodent models have shown that initiation of bladder overactivity using chemical agents, such as cyclophosphamide, can induce hypersensitivity of the colon and conversely induction of colitis can lead to altered bladder function resembling OAB (Bielefeldt K et al., Brumovsky PR et al., Pezzone MA et al.). The concurrence of these disorders suggests that there may be a common underlying pathology or dysfunction at least in a subset of patients.

One theory put forward to explain the concurrence of OAB and IBS is that of cross-organ sensitisation, whereby sensory innervation of the bladder and bowel interact. These interactions can occur at multiple levels. In the periphery, there is evidence for afferent fibres, which extensively branch and innervate multiple target structures. These dichotomising afferents converge at a single neurone in the dorsal root ganglion (DRG). Studies using retrograde tracers injected into the colon and bladder wall have identified specific DRGs neurones that receive projections from both organs, although the numbers or these neurones are low. Sensitisation of the endings in one organ by local inflammation damage or injury would probably impact on overall sensitivity after upregulation in excitability in all terminal receptive fields.

In addition to peripheral mechanisms, sensitisation of central pathways could also be a contributing factor in cross-organ sensitisation. Spinal neurones receiving afferent input from the bladder have been shown to respond to afferent input from other pelvic structures including the colon. Second-order neurones in the spinal cord therefore receive convergent input from various visceral structures, as well as somatic inputs. This theory provides an explanation for the phenomenon of referred pain, where sensations from the viscera are experienced in the associated somatic sensory fields. Such viscero-somatic convergence has been extensively investigated (the most common example of this is angina), but only recently has viscero-visceral referral received attention. Clearly much research is still required to understand these interactions; however; this study clearly highlights the concurrence of bladder and bowel disorders. Understanding the mechanism(s) involved could have important implications for future therapeutic interventions aimed at treating both OAB and IBS.

Donna Daly and Christopher Chapple*

Department of Biomedical Science, University of Sheffeld and *Department of Urology, The Royal Hallamshire Hospital, Sheffeld Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Article of the week: Prolonged SNM testing effective despite bacteria presence

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Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Prolonged percutaneous SNM testing does not cause infection-related explanation

Bastian Amend, Jens Bedke, Mahmoud Khalil, Arnulf Stenzl and Karl-Dietrich Sievert

Department of Urology, Eberhard Karls University Tuebingen, Tuebingen, Germany

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OBJECTIVE

• To evaluate the impact of prolonged stage 1 testing on bacterial electrode colonization, infection and treatment success.

MATERIALS AND METHODS

• In all, 21 patients who underwent sacral neuromodulation (SNM) for periods 1 month were prospectively evaluated; nine patients had overactive bladder syndrome (OAB), 10 had urinary retention, two had faecal incontinence (FI), and 13 had diabetes and overweight/obesity.

• After stage 1 testing electrode extension leads were microbiologically analysed to assess bacterial colonization.

• The primary measurements were pre- and post-SNM treatment comparisons based on patient-agreed criteria using an increased 70% minimum improvement rate; secondary measurements were bacterial colonization and impact of infection.

RESULTS

• The mean stage 1 evaluation period was 52.3 days; 16 patients (76%) progressed to stage 2, and five patients were explanted due to inadequate improvement (<70%).

• There was bacterial colonization in 42.9% of patients and 38.2% of extension leads.

• Stage 2 patients showed no infection or wound-healing disorders at a mean follow-up of 33.9 months.

• The success rate for stage 2 implantation treatment was 94%.

CONCLUSIONS

• There are few studies in the literature evaluating SNM testing periods vs the risk of clinically relevant implant infection rates. The present study shows that prolonged testing could potentially enhance treatment efficacy without infection-related explantations of the chronic implant, despite the identification of bacteria.

• SNM-implanted patients with diabetes mellitus or obesity should be followed closely.

• Clinicians might consider using prolonged testing under everyday conditions.

• Prolonged SNM stage 1 testing is a very effective minimally invasive treatment option to evaluate pelvic-related dysfunction.

 

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