Share this article on:

High satisfaction with direct switching from antimuscarinics to mirabegron in patients receiving stable antimuscarinic treatment

Liao, Chun-Hou PhD, MD; Kuo, Hann-Chorng MD

Section Editor(s): Manchia., Mirko

doi: 10.1097/MD.0000000000004962
Research Article: Observational Study

Abstract: Mirabegron, which was the first β3-adrenoceptor agonist introduced for use in clinical practice, has been extensively evaluated in overactive bladder (OAB) patients in several phase II and III studies. However, most of the enrolled patients were treatment naive or had experienced a wash-out period before the introduction of mirabegron. No study has reported the treatment results of a direct switch from antimuscarinics to mirabegron, which may more commonly occur in clinical practice. This is an observational study to assess the therapeutic efficacy and safety of directly switching from antimuscarinics to mirabegron in patients with OAB receiving stable antimuscarinic treatment. Moreover, we sought to identify the patients who benefited more from the change.

Patients aged ≥20 years with OAB receiving stable antimuscarinics for >3 months were enrolled. Antimuscarinics were discontinued in all patients and mirabegron 25 mg, once daily was initiated. Primary end-point was global response assessment (GRA) at 1 month after medication switching. Baseline parameters and parameters changed 1 month after medication switching were compared between patients with GRA ≥ 1 and GRA < 1.

Of the 282 enrolled patients (209 men, 73 women; mean age, 74.4 years), 55.3% had better (GRA ≥ 1), 31.2% had similar (GRA = 0), and 10.3% had worse (GRA < 0) outcomes. The overall adverse events (AE) rate decreased from 24.1% to 12.8%. In overall patients, there was no significant improvement of OAB symptoms, but postvoid residual (PVR) urine decreased and voiding symptoms and quality of life index improved significantly. Patients with GRA ≥ 1 had significantly improved both storage and voiding symptoms. A total of 195 patients (69.1%) can maintain mirabegron without adding or resuming antimuscarinics for more than 3 months. Logistic regression analysis indicated that higher baseline OAB symptoms scores were predictor of satisfactory outcome.

More than 50% patients exhibited better outcomes after switching from antimuscarinics to mirabegron. Significantly lower AE rates and decreased PVR were noted. Higher baseline OAB symptom scores may predict a better outcome.

aDivision of Urology, Department of Urology, Cardinal Tien Hospital and School of Medicine, Fu-Jen Catholic University

bDepartment of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.

Correspondence: Hann-Chorng Kuo, Department of Urology, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung Yang Road, Hualien, Taiwan (e-mail: hck@tzuchi.com.tw).

Abbreviations: AE = adverse events, 5ARI = 5α-reductase inhibitor, GRA = global response assessment, IPSS = international prostate symptom score, IPSS-S = IPSS storage subscore, IPSS-V = IPSS voiding subscore, OAB = overactive bladder, OAB-SS = overactive bladder symptom score, PPBC = patient perception of bladder condition, PPIUS = patient perception on intensity of urgency scale, PVR = postvoid residual, QoL-I = quality of life index, UTI = urinary tract infection.

The authors have no funding and conflicts of interest to disclose.

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Received May 12, 2016

Received in revised form August 26, 2016

Accepted September 2, 2016

Back to Top | Article Outline

1 Introduction

Overactive bladder (OAB) syndrome is characterized by the presence of urinary urgency, with or without urgency urinary incontinence, and is usually accompanied by frequency and nocturia.[1] Antimuscarinic agents are the standard 1st-line treatment for OAB syndrome.[2,3] This medication has been suggested to reduce detrusor activity and improve bladder capacity via additional mechanisms, including the direct inhibition of afferent signaling at the level of the urothelium and suburothelium.[4] However, some patients may have a suboptimal response to antimuscarinics or may experience adverse events (AEs) such as dry mouth or constipation.[5,6] Therefore, a high proportion of patients discontinue antimuscarinics, and fewer than 25% continue treatment after1 year.[7]

Beta3-adrenoceptors are the predominant β-receptor subtype in human's urinary bladder[8] and are known to promote urine storage by inducing detrusor relaxation.[9,10] Mirabegron, which was the 1st β3-adrenoceptor agonist introduced for use in clinical practice, differs from antimuscarinic agents in its mechanism of action.[11] Mirabegron has been extensively evaluated in more than 5500 patients with OAB syndrome in phase II and III studies.[12] These studies demonstrated significant improvements in micturition frequency, urgency incontinence, and mean volume voided/micturition, and these effects were maintained throughout the treatment course. Moreover, mirabegron appeared to be well tolerated by most patients.[13]

Although several clinical trials have evaluated the efficacy and safety of mirabegron in OAB patients,[13] most of the enrolled patients were treatment naive or had experienced a wash-out period before the introduction of mirabegron. In clinical practice, we usually switch one medication to another one directly. However, no study has reported the treatment results of a direct switch from antimuscarinics to mirabegron. Such an investigation would yield useful information regarding the proportion of patients who would benefit from this treatment strategy in the real world setting. Hence, in the present study, we aimed to assess the therapeutic efficacy and safety of directly switching medication from antimuscarinics to mirabegron without any washout period. Moreover, we sought to identify which patients benefited more from the change.

Back to Top | Article Outline

2 Materials and methods

We enrolled 282 patients aged ≥20 years with OAB who were receiving stable antimuscarinics (solifenacin or tolterodine) for >3 months from 2014 to 2015. Antimuscarinics were discontinued in all patients, and mirabegron (25 mg once daily, which was the recommended initial dose in Taiwan) was initiated. Other concomitant medications, such as α-blockers or 5α-reductase inhibitors (5ARIs), were continuously administered at a stable dose. In the study period, discontinuation of mirabegron, resuming, or adding antimuscarinics can be chosen by physicians and patients because of AEs or poor response to mirabegron. The exclusion criteria were stress urinary incontinence as a predominant symptom at screening; urinary tract infection (UTI), urinary stone, interstitial cystitis, or a history of recurrent UTI; overt bladder outlet obstruction that was not adequately controlled; and other severe medical diseases that prevented patients from undergoing a clinical investigation. The institutional review board and ethics committee of the hospital approved this study. The study rationale was explained to each patient, and written informed consent was obtained prior to treatment.

The treatment results were assessed by using GRA, international prostate symptom score (IPSS) and subscores, overactive bladder symptom score (OAB-SS), patient perception on intensity of urgency scale (PPIUS), patient perception of bladder condition (PPBC), and quality of life index (QoL-I) at 1 and 3 months after medication switching. Patients rated their symptoms after medication switching as compared to that at baseline by using a validated GRA scale, which comprises of 7 points, from markedly worse (−3) to markedly improved (+3).[14,15] The safety assessments included the reporting of AEs, clinical laboratory assessments, vital signs, physical examination, and measurement of postvoid residual (PVR) volume.

The primary endpoint was the GRA at 1 month after medication switching. Changes in parameters such as IPSS, OAB-SS, PPIUS, PPBC, and QoL-I from baseline to 1 and 3 months after medication switching were also assessed. Patients with GRA ≥ 1 at 1 month were considered to have an improved outcome. The secondary endpoints included comparisons of the baseline parameters, and parameters changed 1 month after medication switching between patients with a GRA ≥ 1 and GRA < 1 to determine predictors of improved outcome.

Back to Top | Article Outline

2.1 Statistical analysis

The sample size calculations were based on our previous studies with antimuscarinics.[14,15] Results were analyzed on an intention-to-treat (ITT) basis and included all patients who had taken at least 1 dose of medication. Missing data were imputed on the principle of last observation carried forward (LOCF). Safety data were analyzed for all randomized patients. Continuous variables are expressed as mean ± standard deviation, whereas categorical data are expressed as number and percentages. Statistical comparisons between the groups were performed using Chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Logistic regression analysis was used to identify the predictors of improved outcome (GRA ≥ 1). All statistical assessments were 2-sided and considered significant at P < 0.05. Statistical analyses were performed using SPSS version 17.0 statistical software (SPSS Inc., Chicago, IL).

Back to Top | Article Outline

3 Results

A total of 282 patients (209 men and 73 women; mean age, 74.4 years) were enrolled, including 112 patients (39.7%) classified as OAB wet and 80 patients (28.4%) with detrusor overactivity. Moreover, 192 patients (68.1%) had ≥1 comorbidities including 72 (25.5%) with diabetes, 9 (3.2%) with chronic obstructive pulmonary disease, 19 (6.7%) with coronary artery disease, 12 (4.3%) with cerebral vascular accident, 17 (6.0%) with chronic kidney disease, and 151 (72.2% of male patients) with benign prostatic enlargement. Sixty patients (28.7%) were taking α-blockers, 1 patient (0.4%) was taking 5ARI, and 18 patients (8.6%) were taking both α-blockers and 5ARI along with medication for OAB. The mean duration of the antimuscarinic therapy before the switching was 9.1 months (range, 3–48 months).

At 1 month after medication switching, 54 patients (19.1%) reported marked improvement (GRA = +3), 30 patients (10.6%) reported moderate improvement (GRA = +2), 72 patients (25.5%) reported mild improvement (GRA = +1), 88 patients (31.2%) reported no significant change (GRA = 0), 15 patients (5.3%) reported mild worsening (GRA = −1), 3 patient (1.1%) reported moderate worsening (GRA = −2), and 11 patients (3.9%) reported marked worsening (GRA = −3). Nine patients (3.2%) were lost of followed at 1 month. Of all the patients, 55.3% exhibited better outcomes (GRA ≥ 1) after medication switching, 31.2% exhibited similar outcomes (GRA = 0), and only 10.3% exhibited worse outcomes (GRA < 0). Of the 273 followed patients at 1 month after medication switching, 237 patients (84.0%) kept mirabegron use without antimuscarinics. Seventeen patients (6.0%) discontinued mirabegron and resumed antimuscarinis while 16 patients (5.7%) received “add-on” antimuscarinics with mirabegron after then. Three (1.1%) patients discontinued mirabegron and received other treatment.

Of the 237 patients with mirabegron for more than 1 month, 26 (9.2%) were lost of followed, and 211 patients (74.8%) were followed at 3 months after medication switching. A total of 195 (69.1%) kept mirabegorn use without adding antimuscarinics for more than 3 months. Ten patients (3.5%) received “add-on” antimuscrinics with mirabegron, 4 patients (1.4%) discontinued mirabegron and resumed antimuscarinics, and 2 patients (0.7%) discontinued mirabegron and received other treatment.

When comparing the baseline parameters with those at 1 and 3 months after medication switching (Table 1), we observed that the total IPSS and IPSS voiding subscore (IPSS-V) decreased significantly after medication switching. Moreover, the QoL-I and PPBC also significantly decreased. However, there was no significant change in the measurements of storage symptoms, such as IPSS storage subscore (IPSS-S), nocturia, OAB-SS, and PPIUS in overall patients. Furthermore, no significant change was observed in voided volume and Qmax, although the average PVR decreased significantly after switching medication.

When we separated patients into those with GRA ≥ 1 and GRA < 1, patients with GRA ≥ 1 had significantly decreased total IPSS (IPSS-T), IPSS-V, IPSS-S, nocturia, QoL-I, OAB-SS, and PPBC after medication switching. In contrast, patients with GRA < 1 had significantly increased QoL-I, OAB-SS, and PPBC. There were no significantly change of Qmax, voided volume, and PPIUS. The average PVR decreased significantly in both groups (Table 2).

In addition, 68 patients (24.1%) had ≥1 AE with antimuscarinics, including 31 (11.0%) with dry mouth, 22 (7.8%) with constipation, 20 (7.1%) with dysuria, 3 (1.1%) with slow stream, 2 (0.7%) with blurred vision, and 1 (0.4%) with dizziness (Fig. 1A). After medication switching, 35 patients (12.8%) reported AEs such as dry mouth in 7 (2.6%), constipation in 5 (1.8%), dysuria in 6 (2.2%), slow stream in 2 (0.7%), dizziness in 4 (1.5%), general weakness in 2 (0.7%), back pain in 2 (0.7%), hypertension in 2 (0.7%), UTI in 1 (0.4%), headache in 1 (0.4%), and epigastralgia in 1 (0.4%) (Fig. 1B). All the AEs were mild and tolerable. The rate of AEs decreased from 24.1% to 12.8% after medication switching. In particular, the rate of dry mouth, constipation, and dysuria decreased significantly.

When comparing the baseline parameters between patients with GRA ≥ 1 and GRA < 1 after medication switching, we observed that patients with GRA ≥ 1 had higher baseline IPSS-S, OAB-SS, and PPBC values (Table 3). The other baseline parameters were similar between these 2 groups. Logistic regression analysis also indicated that baseline IPSS-S (odds ratio [OR] = 1.114, P = 0.018) and OAB-SS (OR = 1.103, P = 0.010) could serve as predictors of satisfactory outcome (GRA ≥ 1).

Back to Top | Article Outline

4 Discussions

To our knowledge, this is the 1st study to investigate the treatment results of direct switching from antimuscarinic to mirabegron treatment in patients receiving stable antimuscarinics. Otsuki et al[16] reported mirabegron was effective in 61.6% of patients unresponsive to antimuscarinics, and a significant decrease of OAB-SS and IPSS QoL-I was observed. In another posthoc subgroup analysis,[17] mirabegron treatment was found to be beneficial for OAB patients who were antimuscarinic treatment-naive and patients who had received prior antimuscarinic treatment. In the present study, we observed that even in patients receiving stable antimuscarinic treatment, direct switching of medication from antimuscarinics to mirabegron (25 mg, once daily) was safe and effective.

The present study showed that more than 50% patients exhibited better outcomes after medication switching. Although the QoL-I and PPBC values improved significantly, there was no significant change in OAB symptom parameters such as IPSS-S, OAB-SS, and PPIUS in overall patients. This finding suggests that a change in the medication from antimuscarinics to mirabegron (25 mg) in patients receiving stable antimuscarinics may not yield additional improvement of OAB symptoms. Our results are consistent with a previous meta-analysis reporting that mirabegron has similar efficacy to most antimuscarinics.[18] Batista et al[19] also reported that both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences in OAB patients who were dissatisfied with the previous antimuscarinic treatment due to lack of efficacy. An increase in the mirabegron dose from 25 to 50 mg may increase the efficacy of the medication. Nevertheless, further study is needed to confirm whether 50 mg would be better than 25 mg mirabegron in such conditions as direct medication switching.

In our study, patients with GRA ≥ 1 had significantly decreased IPSS-T, IPSS-V, IPSS-S, nocturia, QoL-I, OAB-SS, and PPBC after medication switching, while patients with GRA < 1 had significantly increased QoL-I, OAB-SS, and PPBC. Although there was no significantly change of OAB symptoms in overall population, some patients could have improved OAB symptoms. However, OAB symptoms may get worse in others. The different responses may be attributable to heterogeneous OAB subgroups and different mechanism of action of antimuscarinics and mirabegron. Patients with GRA < 1 may response to antimuscarinics better than mirabegron. Nevertheless, to improve the storage symptoms among these patients, add-on therapy with mirabegron and antimuscarinics may offer an attractive therapeutic option. In fact, Yamaguchi et al[20] reported that mirabegron as an “add-on” therapy to solifenacin yielded significant improvements in OAB symptoms.

Although direct switching medication from antimuscarinics to mirabegron could only result in the improvement of storage symptoms in 55.3% of the patients, the total IPSS and IPSS-V significantly improved. In addition, the PVR significantly decreased, no matter in patients with GRA ≥ 1 or GRA < 1. The improvement in voiding symptoms and decrease in PVR may explain the high rate of satisfaction. It is possible that the detrusor contractility and sustainability could be affected by antimuscarinics but not mirabegron even the average PVR < 100 mL before medication switching. Hence, patients whose voiding efficiency affected by antimuscarinics might have improved voiding condition after switching to mirabegron.

Furthermore, the rate of common AEs due to antimuscarinic treatment, including dry mouth, constipation, and dysuria, also decreased significantly. This decrease in the AE rate may also contribute to the high satisfaction rate. In addition, persistence in a specific drug depends on the fulfillment of patients’ expectations and the occurrence of AE that lead to discontinuation in daily practice. It is known that persistence in antimuscarinic use is poor.[7] Pindoria et al[21] reported 69% of patients persisted with mirabegron, but the persistent rate fell to 48% by 6 months. The commonest reasons for discontinuation are unmet treatment expectations and AEs. In a retrospective claims from a Canadian Private Drug Plan database, patients using mirabegron had statistically significantly higher adherence rate than those using antimuscarinics.[22] The persistence rate at 12 months for mirabegron was 30% to 39%. In our study, 69.1% of patients kept mirabegron use for more than 3 months. Longer follow-up is needed to report the longer persistent rate in such condition. Although cardiovascular safety is a major concern associated with mirabegron, the cardiovascular safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinics in a systematic literature review.[23] The overall AE rates decreased from 24.1% to 12.8% and only 1 patient reported hypertension in our study.

Moreover, we sought to assess which patients would benefit more from the medication switching, and found that higher baseline storage parameters, such as IPSS-S and OAB-SS, can serve as predictors of improved outcome (GRA ≥ 1). These results are consistent with previous reports, wherein storage symptom scores such as IPSS-S or OAB-SS were recommended as predictors of favorable outcomes with antimuscarinics.[24,25] Chapple et al[26] conducted a posthoc analysis in subgroups of patients stratified according to the severity of incontinence at baseline. They observed that the treatment effect increases with an increase in the severity of incontinence. Hence, the severity of incontinence and storage symptoms should be importantly considered prior to the use of mirabegron.

One advantage of the present study is that the results can easily be applied to real world clinical practice as the study mimics the clinical setting. Moreover, the present study found that, although the storage symptoms did not generally improve in overall patients, >50% of patients reported improved outcomes due to a decrease in AE rate and PVR and improvement in voiding symptoms. The major limitation of the present study is the lack of a placebo arm. In particular, we did not compare our results with those of patients who continued to receive antimuscarinics. Hence, it is difficult to conclude that the switching of antimuscarinics to mirabegron is more favorable than the maintenance of antimuscarinic treatment. Nevertheless, the current study describes the results of direct switching from antimuscarinics to mirabegron, and suggests the predictors of improved outcomes.

Back to Top | Article Outline

5 Conclusions

We observed that >50% patients reported better outcomes (GRA ≥ 1) and that a significantly lower AE rate was observed after switching from antimuscarinic to mirabegron treatment. Moreover, a significant decrease in PVR and improvement in voiding symptoms as well as in QoL-I were observed. A total of 195 patients (69.1%) can maintain mirabegron without adding or resuming antimuscarinics for more than 3 months. Higher baseline OAB symptom scores, such as OAB-SS and IPSS-S, might serve as predictors of better outcomes in OAB cases undergoing medication switching from antimuscarinics to mirabegron.

Back to Top | Article Outline

References

1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. Am J Obstet Gynecol 2002; 187:116.
2. Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol 2012; 188:2455.
3. Oelke M, Bachmann A, Descazeaud A, et al. European Association of Urology. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 2013; 64:118.
4. Andersson KE, Chapple CR, Cardozo L. Abrams P, Cardozo L, Khoury S, et al. Pharmacological treatment of urinary incontinence. Incontinence: 4th international consultation on incontinence. Plymouth, UK:Plymbridge Distributors; 2009. 631.
5. Benner JS, Nichol MB, Rovner ES, et al. Patient reported reasons for discontinuing overactive bladder medication. BJU Int 2010; 105:1276.
6. D'Souza AO, Smith MJ, Miller LA, et al. Persistence, adherence, and switch rates among extended-release and immediate-release overactive bladder medications in a regional managed care plan. J Manag Care Pharm 2008; 14:291.
7. Brostrom S, Hallas J. Persistence of antimuscarinic drug use. Eur J Clin Pharmacol 2009; 65:309.
8. Yamaguchi O, Chapple CR. b3-Adrenoceptors in urinary bladder. Neurourol Urodyn 2007; 26:752.
9. Yamanishi T, Chapple CR, Yasuda K, et al. Role of beta-adrenoceptor subtypes in mediating relaxation of the pig bladder trigonal muscle in vitro. Neurourol Urodyn 2003; 22:338.
10. Aizawa N, Igawa Y, Nishizawa O, et al. Effects of CL316,243, a beta3-adrenoceptor agonist, and intravesical prostaglandin E2 on the primary bladder afferent activity of the rat. Neurourol Urodyn 2010; 29:771.
11. Takasu T, Ukai M, Sato S, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl) amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther 2007; 321:642.
12. Chapple CR, Cardozo L, Nitti VW, et al. Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol Urodyn 2014; 33:17.
13. Kuei CH, Peng CH, Liao CH. Perspectives on mirabegron in the treatment of overactive bladder syndrome: a new beta-3 adrenoceptor agonist. Urol Sci 2015; 26:17.
14. Liao CH, Lin VC, Chung SD, et al. Therapeutic effect of (-blockers and antimuscarinics in male lower urinary tract symptoms based on the International Prostate Symptom Score subscore ratio. Int J Clin Pract 2012; 66:139.
15. Liao CH, Kuo HC. How to choose first-line treatment for men with predominant storage lower urinary tract symptoms: a prospective randomised comparative study. Int J Clin Pract 2015; 69:124.
16. Otsuki H, Kosaka T, Nakamura K, et al. β3-Adrenoceptor agonist mirabegron is effective for overactive bladder that is unresponsive to antimuscarinic treatment or is related to benign prostatic hyperplasia in men. Int Urol Nephrol 2013; 45:53.
17. 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.
18. Maman K, Aballea S, Nazir J, et al. Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison. Eur Urol 2014; 65:755.
19. Batista JE, Kölbl H, Herschorn S, et al. The efficacy and safety of mirabegron compared with solifenacin in overactive bladder patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy: results of a noninferiority, randomized, phase IIIb trial. Ther Adv Urol 2015; 7:167.
20. Yamaguchi O, Kakizaki H, Homma Y, et al. Safety and efficacy of mirabegron as ’add-on’ therapy in patients with overactive bladder treated with solifenacin: a post-marketing, open-label study in Japan (MILAI study). BJU Int 2015; 116:612.
21. Pindoria N, Malde S, Nowers J, et al. Persistence with mirabegron therapy for overactive bladder: a real life experience. Neurourol Urodyn 2015; doi: 10.1002/nau.22943. [Epub ahead of print].
22. Wagg A, Franks B, Ramos B, et al. Persistence and adherence with the new beta-3 receptor agonist, mirabegron, versus antimuscarinics in overactive bladder: early experience in Canada. Can Urol Assoc J 2015; 9:343.
23. Rosa GM, Ferrero S, Nitti VW, et al. Cardiovascular Safety of β3-adrenoceptor agonists for the treatment of patients with overactive bladder syndrome. Eur Urol 2016; 69:311–323.
24. Liao CH, Kuo YC, Kuo HC. Predictors of successful first-line antimuscarinic monotherapy in men with enlarged prostate and predominant storage symptoms. Urology 2013; 81:1030.
25. Hsiao SM, Liao CH, Lin HH, et al. Duration of antimuscarinic administration for treatment of overactive bladder before which one can assess efficacy: an analysis of predictive factors. Int Neurourol J 2015; 19:171.
26. Chapple C, Khullar V, Nitti VW, et al. Efficacy of the (3-adrenoceptor agonist mirabegron for the treatment of overactive bladder by severity of incontinence at baseline: a post hoc analysis of pooled data from three randomised phase 3 trials. Eur Urol 2015; 67:11.
Keywords:

adrenergic beta-3 receptor agonists; muscarinic antagonists; overactive; urinary bladder

Copyright © 2016 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.