Tag Archive for: overactive bladder

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Residents’ Podcast: Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe UUI related to OAB

Part of the BURST/BJUI Podcast Series

Nikita Bhatt is a Specialist Trainee in Urology in the East of England Deanery and a BURST Committee member @BURSTUrology

Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: post hoc analysis of a randomized, placebo‐controlled, double‐blind, comparative phase 3 study

Masaki Yoshida*, Masayuki Takeda, Momokazu Gotoh, Osamu Yokoyama§, Hidehiro Kakizaki, Satoru Takahashi**, Naoya Masumori††, Shinji Nagai‡‡ and Kazuyoshi Minemura‡‡

*Department of Urology, National Centre for Geriatrics and Gerontology, Obu, Department of Urology, University of Yamanashi, Graduate School of Medical Sciences, Kofu, Japan, Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, §Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Department of Renal and Urological Surgery, Asahikawa Medical University, Asahikawa, Japan, **Department of Urology, Nihon University School of Medicine, Tokyo, ††Department of Urology, Sapporo Medical University School of Medicine, Sapporo, and ‡‡Kyorin Pharmaceutical Co., Ltd., Tokyo, Japan

Abstract

Objective

To evaluate the efficacy of a novel and selective β3‐adrenoreceptor agonist vibegron on urgency urinary incontinence (UUI) in patients with overactive bladder (OAB).

Patients and Methods

post hoc analysis was performed in patients with UUI (>0 episodes/day) who were assigned to receive vibegron or placebo in a vibegron phase 3 study. Patients were subclassified into mild/moderate (>0 to <3 UUI episodes/day) or severe UUI (≥3 UUI episodes/day) subgroup. Changes from baseline in number of UUI episodes/day, in number of urgency episodes/day, and in voided volume/micturition were compared between the groups. The percentage of patients who became UUI‐free (‘diary‐dry’ rate) and the response rate (percentage of patients with scores 1 [feeling much better] or 2 [feeling better] assessed by the Patient Global Impression scale [PGI]) were evaluated.

Results

Changes in numbers of UUI episodes at week 12 in the vibegron 50 mg, vibegron 100 mg and placebo groups, respectively, were −1.35, −1.47 and −1.08 in all patients, −1.04, −1.13 and −0.89 in the mild/moderate UUI subgroup, and −2.95, −3.28 and −2.10 in the severe UUI subgroup. The changes were significant in the vibegron 50 and 100 mg groups vs placebo regardless of symptom severity. Change in number of urgency episodes/day was significant in the vibegron 100 mg group vs placebo in all patients and in both severity subgroups. In the vibegron 50 mg group, a significant change vs placebo was observed in all patients and in the mild/moderate UUI subgroup. Change in voided volume/micturition was significantly greater in the vibegron 50 and 100 mg groups vs placebo in all patients, as well as in the both severity subgroups. Diary‐dry rates in the vibegron 50 and 100 mg groups were significantly greater vs placebo in all patients and in the mild/moderate UUI subgroup. In the severe UUI subgroup, however, a significant difference was observed only in the vibegron 50 mg group. Response rates assessed by the PGI were significantly higher in the vibegron groups vs placebo in all patients and in the both severity subgroups. Vibegron administration, OAB duration ≤37 months, mean number of micturitions/day at baseline <12.0 and mean number of UUI episodes/day at baseline <3.0 were identified as factors significantly associated with normalization of UUI.

Conclusions

Vibegron, a novel β3‐adrenoreceptor agonist, significantly reduced the number of UUI episodes/day and significantly increased the voided volume/micturition in patients with OAB including those with severe UUI, with the response rate exceeding 50%. These results suggest that vibegron can be an effective therapeutic option for OAB patients with UUI.

Article of the week: Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe UUI related to OAB: post hoc analysis of a randomized, placebo‐controlled, double‐blind, comparative phase 3 study

Every week, the Editor-in-Chief selects an 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 this post, there is an editorial written by a prominent member of the urological community and a video produced by the authors. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: post hoc analysis of a randomized, placebo‐controlled, double‐blind, comparative phase 3 study

 

Masaki Yoshida*, Masayuki Takeda, Momokazu Gotoh, Osamu Yokoyama§, Hidehiro Kakizaki, Satoru Takahashi**, Naoya Masumori††, Shinji Nagai‡‡ and Kazuyoshi Minemura‡‡

*Department of Urology, National Centre for Geriatrics and Gerontology, Obu, Department of Urology, University of Yamanashi, Graduate School of Medical Sciences, Kofu, Japan, Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, §Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Department of Renal and Urological Surgery, Asahikawa Medical University, Asahikawa, Japan, **Department of Urology, Nihon University School of Medicine, Tokyo, ††Department of Urology, Sapporo Medical University School of Medicine, Sapporo, and ‡‡Kyorin Pharmaceutical Co., Ltd., Tokyo, Japan

Abstract

Objective

To evaluate the efficacy of a novel and selective β3‐adrenoreceptor agonist vibegron on urgency urinary incontinence (UUI) in patients with overactive bladder (OAB).

Patients and Methods

post hoc analysis was performed in patients with UUI (>0 episodes/day) who were assigned to receive vibegron or placebo in a vibegron phase 3 study. Patients were subclassified into mild/moderate (>0 to <3 UUI episodes/day) or severe UUI (≥3 UUI episodes/day) subgroup. Changes from baseline in number of UUI episodes/day, in number of urgency episodes/day, and in voided volume/micturition were compared between the groups. The percentage of patients who became UUI‐free (‘diary‐dry’ rate) and the response rate (percentage of patients with scores 1 [feeling much better] or 2 [feeling better] assessed by the Patient Global Impression scale [PGI]) were evaluated.

Diary‐dry rate. UUI, urgency urinary incontinence. Data are presented as mean (95% CI). Chi‐squared test, *P < 0.05, **P < 0.001 vs placebo. PBO, placebo group; V 100, vibegron 100 mg group; V 50, vibegron 50 mg group; Wk, week(s).

Results

Changes in numbers of UUI episodes at week 12 in the vibegron 50 mg, vibegron 100 mg and placebo groups, respectively, were −1.35, −1.47 and −1.08 in all patients, −1.04, −1.13 and −0.89 in the mild/moderate UUI subgroup, and −2.95, −3.28 and −2.10 in the severe UUI subgroup. The changes were significant in the vibegron 50 and 100 mg groups vs placebo regardless of symptom severity. Change in number of urgency episodes/day was significant in the vibegron 100 mg group vs placebo in all patients and in both severity subgroups. In the vibegron 50 mg group, a significant change vs placebo was observed in all patients and in the mild/moderate UUI subgroup. Change in voided volume/micturition was significantly greater in the vibegron 50 and 100 mg groups vs placebo in all patients, as well as in the both severity subgroups. Diary‐dry rates in the vibegron 50 and 100 mg groups were significantly greater vs placebo in all patients and in the mild/moderate UUI subgroup. In the severe UUI subgroup, however, a significant difference was observed only in the vibegron 50 mg group. Response rates assessed by the PGI were significantly higher in the vibegron groups vs placebo in all patients and in the both severity subgroups. Vibegron administration, OAB duration ≤37 months, mean number of micturitions/day at baseline <12.0 and mean number of UUI episodes/day at baseline <3.0 were identified as factors significantly associated with normalization of UUI.

Conclusions

Vibegron, a novel β3‐adrenoreceptor agonist, significantly reduced the number of UUI episodes/day and significantly increased the voided volume/micturition in patients with OAB including those with severe UUI, with the response rate exceeding 50%. These results suggest that vibegron can be an effective therapeutic option for OAB patients with UUI.

Editorial: Guidelines on urinary incontinence: it is time to join forces!

Urinary incontinence is not life‐threatening and does not kill patients, but it is highly prevalent affecting millions of people worldwide, it significantly impairs quality of life, and the related health‐care costs are enormous. Thus, guidelines are crucial for helping us to achieve an optimal management of our patients with urinary incontinence.

In this month’s issue of the BJUI, Sussman et al. present a Guideline of Guidelines on urinary incontinence in women. They reviewed the guidelines of the American College of Obstetrics and Gynecology (ACOG) / American Urogynecologic Society (AUGS), American Urological Association (AUA) / Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU), European Association of Urology (EAU), International Consultation on Incontinence (ICI), and National Institute for Health and Care Excellence (NICE). The recommendations of the different guidelines were similar for the initial evaluation and conservative therapies but differed considerably in some points of invasive management. In brief, the most essential issues are the following: Basic work‐up includes detailed history taking and specifying the type of urinary incontinence, urodynamics is performed when it changes management and in cases of recurrent urinary incontinence after interventions, treatment follows a stepwise approach starting with conservative therapy and moving to invasive options as appropriate, and treatment of women with mixed urinary incontinence is focused on the predominant symptom.

Although the management of urinary incontinence is well defined and excellently summarised by Sussman et al., treatment often remains demanding in daily clinical practice due to insufficient effectiveness or relevant side effects, so that new therapeutic options are urgently needed. Vibegron is a novel β3‐adrenoreceptor agonist, and Yoshida et al. present in the current issue of the BJUI promising findings with this drug for treating severe urgency urinary incontinence related to overactive bladder. In a post hoc analysis of a randomised, placebo‐controlled, double‐blind, comparative phase 3 study, vibegron significantly reduced the number of urgency urinary incontinence episodes and significantly increased voided volume per micturition with a response rate exceeding 50% [Yoshida et al]. These results are encouraging and warrant further randomised controlled trials, but also vibegron seems not to be a miracle agent showing effects in the range of mirabegron or antimuscarinics. However, there is some light at the end of the tunnel: Closed‐loop optogenetic neuromodulation systems targeting specific neurons to control urinary tract function might completely revolutionise the field, although there are still relevant hurdles to overcome.

Guidelines should result from a rigorous and transparent process informed by the best available up‐to‐date evidence and safeguarded against biases and conflict of interests. This is a major challenge, and from a bird’s eye view, it is hard to comprehend that several guidelines on the same topic exist and it is even more difficult to understand that the recommendations of these guidelines are not congruent and sometimes even contradictory. For instance, in the case of a pelvic organ prolapse repair in a continent woman, the ACOG / AUGS, AUA / SUFU, and EAU guidelines discuss prophylactic anti‐incontinence surgery as an option, whereas ICI and NICE guidelines explicitly recommend against it. The redundancy is enormous, but societies and organisations still create their own guidelines – an unnecessary waste of resources. In recent times, the coronavirus pandemic has rapidly changed our life and paralysed our usual activities, we have to stand together, it is definitively time to join forces! The relevant societies and organisations should consult each other and coordinate their efforts. Together we are strong, let’s move forward to joint guidelines!

Video: Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder

Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: post hoc analysis of a randomized, placebo‐controlled, double‐blind, comparative phase 3 study

Abstract

Objective

To evaluate the efficacy of a novel and selective β3‐adrenoreceptor agonist vibegron on urgency urinary incontinence (UUI) in patients with overactive bladder (OAB).

Patients and Methods

post hoc analysis was performed in patients with UUI (>0 episodes/day) who were assigned to receive vibegron or placebo in a vibegron phase 3 study. Patients were subclassified into mild/moderate (>0 to <3 UUI episodes/day) or severe UUI (≥3 UUI episodes/day) subgroup. Changes from baseline in number of UUI episodes/day, in number of urgency episodes/day, and in voided volume/micturition were compared between the groups. The percentage of patients who became UUI‐free (‘diary‐dry’ rate) and the response rate (percentage of patients with scores 1 [feeling much better] or 2 [feeling better] assessed by the Patient Global Impression scale [PGI]) were evaluated.

Results

Changes in numbers of UUI episodes at week 12 in the vibegron 50 mg, vibegron 100 mg and placebo groups, respectively, were −1.35, −1.47 and −1.08 in all patients, −1.04, −1.13 and −0.89 in the mild/moderate UUI subgroup, and −2.95, −3.28 and −2.10 in the severe UUI subgroup. The changes were significant in the vibegron 50 and 100 mg groups vs placebo regardless of symptom severity. Change in number of urgency episodes/day was significant in the vibegron 100 mg group vs placebo in all patients and in both severity subgroups. In the vibegron 50 mg group, a significant change vs placebo was observed in all patients and in the mild/moderate UUI subgroup. Change in voided volume/micturition was significantly greater in the vibegron 50 and 100 mg groups vs placebo in all patients, as well as in the both severity subgroups. Diary‐dry rates in the vibegron 50 and 100 mg groups were significantly greater vs placebo in all patients and in the mild/moderate UUI subgroup. In the severe UUI subgroup, however, a significant difference was observed only in the vibegron 50 mg group. Response rates assessed by the PGI were significantly higher in the vibegron groups vs placebo in all patients and in the both severity subgroups. Vibegron administration, OAB duration ≤37 months, mean number of micturitions/day at baseline <12.0 and mean number of UUI episodes/day at baseline <3.0 were identified as factors significantly associated with normalization of UUI.

Conclusions

Vibegron, a novel β3‐adrenoreceptor agonist, significantly reduced the number of UUI episodes/day and significantly increased the voided volume/micturition in patients with OAB including those with severe UUI, with the response rate exceeding 50%. These results suggest that vibegron can be an effective therapeutic option for OAB patients with UUI.

Article of the Month – Guidelines of the Guidelines: Urinary Incontinence in Women

Every month, the Editor-in-Chief selects an Article of the Month 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 editorial prepared by a prominent member of the urological community and a video by the authors; 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 month, we recommend this one. 

Guidelines of the Guidelines: Urinary Incontinence in Women

Rachael D. Sussman*, Raveen Syan and Benjamin M. Brucker
*Department of Urology, MedStar Georgetown University Hospital, Washington, DC, Department of Urology, Stanford School of Medicine, Stanford, CA, and Department of Urology, New York University Medical Center, New York, NY, USA

Introduction

Urinary incontinence (UI) is a common disease, with prevalence rates as high as 44–57% in middle‐aged and post‐menopausal women. Those with UI may experience physical, functional, and psychological limitations and diminished quality of life (QoL) at home and at work. The financial burden of UI care is significant, with an estimated direct cost of $19.5 billion (American dollars) in the USA alone.

UI can be classified into a number of different categories, with stress UI (SUI) and urgency UI (UUI) being the most common. Many professional organisations have created guidelines to help clinicians navigate the diagnosis and evaluation of UI, as well as the treatments including conservative, pharmacological, and surgical. The methodologies upon which most guidelines are based are similar, starting with systematic reviews and grading of available literature. Organisations then make recommendations with different definitions and strengths. Guidelines are not exhaustive, but rather serve as a practical review of evidence‐based management of ‘index patients’.

The present ‘Guideline of guidelines,’ updated from a 2016 publication, reviews various international guidelines that have been updated at different time intervals and provides an updated summary of the important similarities and differences on the management of UI in women.

Editorial: Oxidative stress and lower urinary tract symptoms: cause or consequence?

Oxidative stress has been defined as ‘an imbalance between oxidants and anti-oxidants in favour of the oxidants, leading to a disruption of redox signalling and control and/or molecular damage’ [1]. Reactive oxygen and nitrogen species (ROS/RNS) produced under oxidative stress are known to damage all cellular biomolecules (lipids, sugars, proteins and polynucleotides). ROS/RNS is often used as a generic term but it has been emphasized that all ROS/RNS molecules are not the same [2] and the term encompasses a diverse range of species, including, for example, superoxide, hydrogen peroxide, nitric oxide and peroxynitrite. The biological impacts of ROS/RNS depend critically on the particular molecule(s) involved, and on the microenvironment and physiological or pathological context in which it is being generated [2]. It should be emphasized that ROS are not only harmful agents that cause oxidative damage in pathologies but they also have important roles as regulatory agents in a range of biological phenomena. They are normally generated as by-products of oxygen metabolism; however, environmental stressors (ultraviolet radiation, ionizing radiations, pollutants, heavy metal and xenobiotics) contribute to greatly increase ROS/RNS production.

It is difficult to measure ROS/RNS, therefore, biomarkers are often used as a surrogate; however, many of the biomarkers are insufficiently validated and it is often difficult to draw general conclusions on their significance [3]. 8-OHdG, one of the major products of DNA oxidation, is one of the most commonly used biomarkers of oxidative stress. Advanced glycation end-products (AGEs) are a group of heterogeneous molecules that arise from the non-enzymatic reaction of reducing sugars with amino groups of lipids, DNA and especially long-lived proteins. This process occurs during normal metabolism but is even more pronounced under oxidative stress conditions. AGEs may be harmful and include modified proteins and/or lipids with damaging potential. Using 8-OHdG, AGEs and other biomarkers, several attempts have been made to link oxidative stress, either as a cause or contributor, or both, to a variety of diseases, including LUTS. As pointed out by Ghezzi et al. [4] ‘Today it is a challenge to find a disease for which a role of oxidative stress has not been postulated.’

Matsumoto et al. [5] investigated the possible relationship between some markers of oxidative stress and LUTS in a population of community-living subjects participating in a health promotion project. As markers of oxidative stress, they used 8-OHdG (urine) and AGEs (skin autofluorescence), while structured questionnaires were used to assess LUTS. In their study, despite univariate analyses revealing several significant associations, multivariate analyses showed that the only statistically significant finding was that AGEs were associated with moderate to severe nocturia. This association is thought-provoking but, without functional studies, difficult to evaluate. LUTS are multifactorial and reflect a number of different comorbidities/pathophysiologies. It cannot be excluded that this may contribute to the lack of associations between oxidative stress markers and symptoms.

The finding of an association (or lack of it) between biomarkers of oxidative stress and LUTS does not reveal whether oxidative stress causes or contributes to LUTS. If ROS/RNS were causative/contributing factors to LUTS, it would be predicted that a positive response to antioxidant therapy and a decrease in ROS/RNS levels would not only support an involvement but would also be a promising treatment approach. In a prospective cohort study in the USA of 1670 men aged 65–100 years, Holton et al. [6] examined whether dietary antioxidants were associated with a reduced likelihood of LUTS progression or an increased likelihood of LUTS. They found that there were no significant associations between multiple dietary antioxidants and LUTS progression or remission over 7 years. Many other attempts to validate and exploit chronic antioxidant therapies have provided disappointing results, and still there is no antioxidant with sufficient efficacy to be approved by health authorities [4]. The question of whether antioxidant therapy may be harmful has not yet been answered. If the cause of LUTS is an increase of ROS/RNS in the bladder, it is questionable whether normalization of indicators of oxidative stress is safe, considering that the normal function of ROS/RNS in the rest of the body may be affected.

The clinical relevance of oxidative stress as a pathophysiological factor in lower urinary tract dysfunction or as a treatment target for various lower urinary tract disorders is still unclear. In addition, it has not been established that antioxidant therapy has any beneficial effect on LUTS.

by Karl-Erik Andersson

References

  1. Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol 2015; 4: 180–3
  2. Murphy MP, Holmgren A, Larsson NG et al. Unraveling the biological roles of reactive oxygen species. Cell Metab 2011; 13: 361–6
  3. Frijhoff J, Winyard PG, Zarkovic N et al. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal 2015; 23: 1144–70
  4. Ghezzi P, Jaquet V, Marcucci F, Schmidt HHHW. The oxidative stress theory of disease: levels of evidence and epistemological aspects. Br J Pharmacol 2017; 174: 1784–96
  5. Matsumoto T, Hatakeyama S, Imai A et al. Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan. BJU Int 2019; 123 877-84
  6. Holton KF, Marshall LM, Shannon J et al. Osteoporotic fractures in men study group. Dietary antioxidants and longitudinal changes in lower urinary tract symptoms in elderly men: the Osteoporotic Fractures in Men study. Eur Urol Focus 2016; 2: 310–8

 

The times they are a-changin’

The other day, as the New York Times was getting excited about Nobel Laureate Bob Dylan new album ‘Triplicate’, I had the opportunity of remembering one of his classic songs. Let me explain. I turned up at the School of Surgery in central London for an academic committee meeting early that morning only to find that it had been cancelled. Due to a IT problem the email with this information never reached me! Rather than brave the London tube again, I decided to walk back to my hospital, which took me past my old hospital which sadly no longer exists.

middlesex-blog

The old hospital in question was The Middlesex Hospital in Mortimer Street, London (Fig.1). The original institution was built in 1745 at Windmill Street and moved in 1757 to Mortimer Street. I arrived there over 20 years ago to train at the Institute of Urology/St. Peter’s Hospital, a highly desirable post amongst surgical residents.

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The Middlesex Hospital was closed in 2005 and sold to developers. It now houses swanky apartments and businesses around a beautiful Pearson Square, named after John Loughborough Pearson, who designed the Fitzrovia Chapel (Fig. 2) in 1890 inside the hospital. The Chapel survived the redevelopment as it is a protected building. So did one of the walls of the old hospital along Nassau Street which housed the radiotherapy building (Fig. 3). That facade has been preserved beautifully although there are no patients housed behind it anymore (Fig. 4).

dc533794-189e-4e5e-91b2-0f6cd0d1ea61

So why I am telling you all this? Nostalgia you may say. But in fact much more. The 3 mile walk that morning allowed me to reflect on my own contribution to science and that of two friends who although slightly ahead of me in the training program at The Middlesex Hospital are gentlemen that I greatly admire.

One is Mark Emberton, now Professor at UCL, who has, through the PROMIS study, established the use of MRI prior to prostate biopsies rather than random TRUS biopsies for patients with a raised PSA. The other is David Ralph, an acclaimed Andrologist, who has just published our Priapism Guidelines, a must read for everyone managing this emergency. There is no doubt that both have made significant contributions to British Urology and patient care in the last 20 years during which so many things have changed.

fb6ee749-c241-471c-8e34-6d979aa61a29

As for me, I headed to Queen Square from The Middlesex Hospital, where many years of basic research in a Medical Research Council (MRC) funded lab led to the description of the so called “Dasgupta technique” of injecting Botox into overactive bladders. I was pleasantly surprised to hear that it had made its way into a number of texts including Smith’s Textbook of Endourology.

There are however certain things that do not change much. Next to the Middlesex Hospital, on Cleveland Street was the legendary Ragam’s (Fig. 5), which many would regard as THE go to South Indian restaurant. The masala dosa (pancake with spicy potatoes and hot lentil soup) used to cost £3.95 in 1994; 20 years later the price has gone up by only £2 to £5.95 (Fig. 6), while the quality remains as outstanding as ever.

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458caf67-1787-450e-bd45-c51f442a23e8

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

In search of the ROSETTA stone (again)?

We are having an amazing year of scientific discovery in our specialty. 2016 has already seen the results of the only randomised trial comparing open versus robotic radical prostatectomy from Australia and the ProtecT trial from UK discussed intensively on [email protected] The PROMIS of MRI is expected to change the practice of prostate biopsies in response to a raised PSA. The teams completing these trials deserve our heartiest congratulations as it is well known how difficult randomised trials in surgery are to initiate and complete.

As if this was not enough, this month the randomised controlled trial comparing Botox (Onabotulinum toxin A) to Interstim (sacral neuromodulation) in patients with refractory overactive bladder has been reported in JAMA. It is otherwise known as the ROSETTA study (Refractory Overactive Bladder:  Sacral NEuromodulation v. BoTulinum Toxin Assessment).

This is an example of what collaboration between individuals and teams within a pelvic floor group can achieve. Cindy Amundsen, the lead author, presented the trial results at the #AUA16 late breaking abstract session in San Diego.

The CONSORT diagram is shown here
rosetta2

The primary outcome measure showing Botox winning over Interstim (narrowly) in reducing urgency urinary incontinence is demonstrated in this diagram.
rosetta3

The summary results are shown here
rosetta1

So what would you do for your patient with refractory overactive bladder who has failed Anticholinergics and Mirabegron?

I have spent the last week thinking about the trial results carefully and was asked exactly this question at the International Endourology Forum in China. There are a number of important aspects to consider. The dose of Botox used in the trial was 200 units while the licensed dose is 100 units for overactive bladder of non-neurogenic origin. We know that one size does not fit all and indeed some patients failing 100 units need higher doses of Botox. It remains unknown as to what would have happened if 100 units of Botox was compared to Interstim as the authors are quite guarded about their own conclusions about the benefits.

The side effects also need to be carefully discussed with the patient. The UTI rate in the Botox group is about three times that of the Interstim group. Most patients may accept a period of oral antibiotics to counter this. The risk of CISC dropped from 8% at 1 month to 2% at 6 months in the Botox group. This is lower than previously reported in Phase lll studies. The need for revision or removal in the Interstim patients was around 3% – small but not to be ignored.

Punchline
If I was the patient in question, I would have Botox initially, preserving Interstim for later. It is less invasive and can be repeated roughly once a year if needed. Call me “lilly livered” but I do not like the idea of having a little box, however tiny, inside my bum and occasionally having to sit on it! I look forward to the smarter new generation of minimally invasive or even non-invasive nerve stimulators. But then it would need another randomised trial, many years of unanswered questions, perhaps even wastage of a lot of grant money…………..yawn!!

In the meantime, I will take my chances with Botox and counsel my patients accordingly. Unlike the famous ROSETTA stone, the key to understanding the mystery behind hieroglyphs and the controversy as to whether it should at all be in the British museum, I fail to see any such controversy with this nice trial in JAMA.

My thoughts and message are clear. Are yours?

 

Article of the Week: Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an alpha-blocker

Every Week the Editor-in-Chief selects an 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 from Dr. Tae Heon Kimdiscussing his paper. 

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

Comparison of the efficacy and safety of tolterodine 2 mg and 4 mg combined with an alpha-blocker in men with lower urinary tract symptoms (LUTS) and overactive bladder: a randomized controlled trial

Tae Heon Kim*, Wonho Jung†, Yoon Seok Suh*, Soonhyun Yook‡, Hyun Hwan Sung* and Kyu-Sung Lee*‡
*Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, †Department of Urology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, and ‡Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea Tae Heon Kim and Wonho Jung contributed equally to this work.

 

Objective
To evaluate the efficacy and safety of low-dose (2 mg) tolterodine extended release (ER) with an a-blocker compared with standard-dose (4 mg) tolterodine ER with an α-blocker for the treatment of men with residual storage symptoms after α-blocker monotherapy.
Patients and Methods
The study was a 12-week, single-blind, randomized, parallel group, non-inferiority trial that included men with residual storage symptoms despite receiving at least 4 weeks of α-blocker
treatment. Inclusion criteria were total International Prostate Symptom Score (IPSS) ≥12, IPSS quality-of-life item score ≥3, and ≥8 micturitions and ≥2 urgency episodes per 24 h. The primary outcome was change in the total IPSS score from baseline. Bladder diary variables, patient-reported
outcomes and safety were also assessed.
feb-2-aotw-f1
Results
Patients were randomly assigned to addition of either 2 mg tolterodine ER (n = 47) or 4 mg tolterodine ER (n = 48) to α-blocker therapy for 12 weeks. Patients in both treatment groups had a significant improvement in total IPSS score (5.5 and 6.3, respectively), micturition per 24 h (1.3 and
1.7, respectively) and nocturia per night (0.4 and 0.4, respectively). Changes in IPSS, bladder diary variables, and patient-reported outcomes were not significantly different between the treatment groups. All interventions were well tolerated by patients.
Conclusions
These results suggest that 12 weeks of low-dose tolterodine ER add-on therapy is similar to standard-dose tolterodine ER add-on therapy in terms of efficacy and safety for patients experiencing residual storage symptoms after receiving α-blocker monotherapy.

 

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