Please summarize national guidelines and clinical trials on the use of mirabegron in neurogenic bladder dysfunction. Can mirabegron be used in patients with spinal cord dysfunction when anticholinergics are contraindicated due to cognitive dysfunction or unacceptable anticholinergic side effects?

Comment by InpharmD Researcher

Current evidence supports mirabegron as a reasonable alternative for selected patients with neurogenic lower urinary tract dysfunction (NLUTD), including those with spinal cord injury (SCI), when anticholinergic therapy is contraindicated because of cognitive impairment or intolerable anticholinergic adverse effects. The 2021 American Urological Association/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction guideline does not specifically address mirabegron, whereas the 2026 European Association of Urology Neuro-urology guideline states that mirabegron provides symptom and quality-of-life improvements comparable to antimuscarinics but, based on available evidence, has not consistently demonstrated improvements in key urodynamic parameters. Multiple reviews and meta-analyses included patients with multiple sclerosis and SCI. It was noted that there were significant improvements in maximum cystometric capacity, patient perception of bladder condition, and several secondary urodynamic and quality-of-life outcomes with mirabegron. Overall, the data supports mirabegron as an effective and well-tolerated treatment option for patients with NLUTD.

Background

The 2021 American Urological Association (AUA)/Society of Urodynamics, Female Pelvic Medicine & Urogenital (SUFU) reconstruction guideline on adult neurogenic lower urinary tract dysfunction focuses on the evaluation, risk stratification, surveillance, and overall management of adults with neurogenic lower urinary tract dysfunction. The panel emphasizes individualized treatment based on neurologic disease, cognition, functional status, and risk of upper urinary tract deterioration; however, it does not address the use of mirabegron specifically. [1]

A 2021 review on neurogenic bladder management recommendations states that mirabegron cannot be recommended or contraindicated over antimuscarinics as first-line oral therapy due to insufficient comparative evidence (conditional recommendation, low quality evidence). Studies in patients with spinal cord injury and multiple sclerosis suggest improvements in incontinence symptoms and, in some reports, bladder compliance; however, several included studies were uncontrolled case series and one trial showed benefit only when mirabegron was combined with desmopressin rather than as monotherapy. Adverse effects were generally well tolerated, with hypertension, tachycardia, urinary tract infections, dizziness, and headache most commonly reported, and monitoring is recommended in patients with cardiovascular disease. Mirabegron also demonstrates lower discontinuation rates and longer persistence compared with antimuscarinic agents, with dosing and drug interaction considerations in renal or hepatic impairment and with cytochrome P450 (CYP450)-mediated medications. [2]

According to the 2026 European Association of Urology (EAU) guidelines on neuro-urology, evidence supporting mirabegron in patients with neurogenic lower urinary tract dysfunction remains limited. Although mirabegron has demonstrated improvements in lower urinary tract symptoms and quality of life comparable to antimuscarinics, available studies in patients with multiple sclerosis and spinal cord injury have not shown significant improvements in urodynamic parameters, including detrusor pressure or maximum cystometric capacity. Mirabegron has generally been well tolerated, with randomized controlled trial data supporting cardiovascular safety in patients with neurogenic detrusor overactivity, and studies in patients with Parkinson disease reporting no worsening of cognitive function and a lower risk of adverse effects compared with antimuscarinic agents. Overall, the guideline emphasizes that mirabegron provides similar symptom-related clinical benefits as antimuscarinic agents but does not improve urodynamic parameters in patients with neurogenic detrusor overactivity (level of evidence 1b). [3]

A 2016 review article discusses the medical management of neurogenic bladder with oral therapy and notes that mirabegron, a selective β3-adrenergic agonist, has a low adverse effect profile due to receptor specificity and is not expected to impair voiding function. Although data in neurogenic bladder populations are limited, studies in men with lower urinary tract symptoms and bladder outlet obstruction showed no significant changes in urine flow or detrusor pressure at maximum flow compared with placebo, with only a small increase in post-void residual at higher doses and no reported urinary retention requiring catheterization or cardiac adverse events. In a small study of patients with neurogenic bladder who failed antimuscarinics, mirabegron added to therapy was associated with improvements in detrusor overactivity, vesicoureteral reflux, and bladder compliance. The review notes that mirabegron is increasingly used in neurogenic patients who void, particularly those at risk for urinary retention from antimuscarinics, with generally mild adverse effects but suggest caution for the small increases in blood pressure and heart rate, and avoidance in patients with uncontrolled hypertension. [4]

A 2018 systematic review and network meta-analysis evaluated the efficacy and tolerability of mirabegron compared with antimuscarinic monotherapy or combination therapy in adults with non-neurogenic overactive bladder (OAB). The review included randomized controlled trials published between 2000 and 2017 with treatment durations of 4–16 weeks and incorporated data from 64 RCTs involving 46,666 participants. Mirabegron 50 mg was significantly more effective than placebo across all efficacy endpoints, including reductions in micturition frequency (mean difference [MD] 0.71; 95% credible interval [CrI] 0.55–0.87), urgency urinary incontinence (UUI) episodes (MD 0.40; 95% CrI 0.26–0.54), dry rate (OR 0.72; 95% CrI 0.64–0.82), and achieving a ≥50% reduction in incontinence episodes (OR 0.67; 95% CrI 0.57–0.79). Overall efficacy was comparable to most antimuscarinic monotherapies, although solifenacin 10 mg and combination therapy with solifenacin 5 mg plus mirabegron (25 mg or 50 mg) demonstrated superior efficacy for some endpoints. [5]

Regarding tolerability, mirabegron demonstrated a more favorable adverse effect profile than most antimuscarinic agents. The risk of dry mouth was significantly lower than 21 of 22 active comparators, constipation was lower than 9 of 20 comparators, and urinary retention was lower than 7 of 10 comparators. Rates of blurred vision, hypertension, urinary tract infection, and tachycardia were generally similar to placebo and other active treatments. The authors noted that mirabegron had similar efficacy to most antimuscarinic agents while avoiding many of the bothersome anticholinergic adverse effects that commonly lead to treatment discontinuation. Although this analysis excluded patients with neurogenic detrusor overactivity and therefore does not directly address neurogenic bladder or spinal cord dysfunction, its findings support mirabegron as an alternative pharmacologic option when avoidance of anticholinergic adverse effects is desirable. [5]

A 2021 systematic review and meta-analysis assessed the efficacy and safety of mirabegron for treating neurogenic lower urinary tract dysfunction (NLUTD). This investigation utilized data from four randomized controlled trials, involving a total of 245 patients with conditions such as spinal cord injury and neurological disorders like multiple sclerosis and Parkinson disease. The primary outcomes evaluated were bladder compliance, urinary incontinence episodes, Incontinence Quality of Life (I-QOL), Patient Perception of Bladder Condition (PPBC), and urinary urgency episodes. Safety outcomes included the incidence of drug-related adverse events, arrhythmias, hypertension, and post-voiding residual volume. The meta-analysis revealed that mirabegron treatment resulted in a significant improvement in bladder compliance (MD 19.53, 95% confidence interval 14.19 to 24.87, p<0.00001], urinary incontinence episodes (MD −0.78, 95% CI −0.89 to −0.67, p<0.00001), and I-QOL (MD 8.02, 95% CI 3.20 to 12.84, p=0.001). However, no significant differences were observed in PPBC or urinary urgency episodes when compared to placebo. Regarding safety, mirabegron did not show a significant difference from placebo in the incidence of adverse events, arrhythmias, hypertension, or changes in post-voiding residual volume. This analysis suggests that mirabegron is an effective and safe treatment for NLUTD, offering an alternative to traditional antimuscarinic therapy. [6]

A 2022 systematic review evaluated the efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity (NDO) in adults suffering from spinal cord injury (SCI) or multiple sclerosis (MS). This review compiled data from 11 studies with a total of 488 patients. These studies varied in design, including 2 randomized, double-blind, placebo-controlled trials; 2 randomized comparative studies; 3 prospective cohort studies; 1 prospective comparative non-randomized study; and 3 retrospective studies. The treatment durations ranged from 4 weeks to 12 months, with mirabegron being used primarily as a second-line treatment following anticholinergics. Results from this systematic review indicated that mirabegron demonstrated similar clinical efficacy to anticholinergics in patients with MS, as evidenced by clinical outcome parameters. However, comprehensive urodynamic evaluations in the studies involving SCI patients, particularly in randomized controlled trials, did not show significant improvements in key urodynamic parameters such as maximum cystometric capacity or detrusor pressure, which are critical for assessing the risk of upper urinary tract deterioration. On the safety front, while mirabegron was generally well-tolerated with no significant changes in heart rate or blood pressure observed across most studies, occasional cardiovascular concerns such as tachycardia were reported. The review highlighted the need for further research, especially multicenter randomized studies, to better assess the role of mirabegron in NDO management, particularly in different subsets of neurogenic bladder patients. [7]

A 2023 systematic review and network meta-analysis evaluated the efficacy and safety of oral detrusor relaxing agents (DRAs), including antimuscarinics and mirabegron, in patients with NDO. The analysis included 23 randomized controlled trials involving 1,697 patients, including 16 trials evaluating antimuscarinics, 5 placebo-controlled trials of mirabegron, and 2 direct comparisons between mirabegron and antimuscarinics. Compared with placebo, oral DRAs were associated with significant improvements in patient perception of bladder condition (standardised mean difference [SMD] −0.509; 95% CI −0.897 to −0.121), incontinence-related quality of life (SMD 0.370; 95% CI 0.136 to 0.605), urinary incontinence episodes (SMD −0.734; 95% CI −1.317 to −0.150), maximum bladder capacity (SMD 0.640; 95% CI 0.210 to 1.069), volume at first contraction (SMD 0.819; 95% CI 0.621 to 1.018), maximum detrusor pressure (SMD −0.498; 95% CI −0.922 to −0.073), and bladder compliance (SMD 0.410; 95% CI 0.131 to 0.688), although total adverse events were more frequent (RR 1.380; 95% CI 1.032–1.846). [8]

In subgroup analyses, antimuscarinics significantly improved patient perception of bladder condition, urinary incontinence episodes, urinary frequency, residual urine volume, maximum bladder capacity, volume at first contraction, maximum detrusor pressure, and bladder compliance, but were associated with a significantly greater risk of adverse events (RR 1.565; 95% CI 1.082–2.263) and xerostomia (RR 4.819; 95% CI 2.340–9.923). Mirabegron significantly improved incontinence-related quality of life (SMD 0.617; 95% CI 0.210–1.023), volume at first contraction (SMD 0.898; 95% CI 0.481–1.315), and bladder compliance (SMD 0.661; 95% CI 0.165–1.158), while no significant differences versus placebo were observed for urinary incontinence episodes, urinary frequency, residual urine volume, maximum bladder capacity, maximum detrusor pressure, or overall adverse events (RR 1.157; 95% CI 0.722–1.854). Two randomized trials directly comparing mirabegron with antimuscarinics found no significant differences in efficacy or safety, and the network meta-analysis similarly found no antimuscarinic agent or mirabegron to be superior or inferior to another across evaluated efficacy and safety outcomes. It was suggested that although mirabegron may provide some clinical benefit with fewer bothersome anticholinergic adverse effects, evidence supporting mirabegron as first-line therapy for NDO remains limited, and additional well-designed randomized trials are needed. [8]

A 2024 individual participant data meta-analysis (IPDMA) analyzed the effects of mirabegron on NLUTD in patients with MS and SCI. The meta-analysis pooled data from two previously published randomized, placebo-controlled trials, which included a total of 98 patients. The primary outcomes evaluated were the change in maximum cystometric capacity and the PPBC. Secondary outcomes were the change in the peak pressure of NDO, volume at first NDO, urodynamic compliance, 24-hour pad weight, and an I‐QoL. The analyses were conducted using analysis of covariance, adjusting for baseline values for statistical robustness. The results highlighted a significant improvement in maximum cystometric capacity by 41 mL (p= 0.04) and in PPBC by 0.8 points in the mirabegron group compared to placebo (p<0.01). Secondary outcomes, such as peak NDO pressure and I-QoL scores, also showed significant improvements with mirabegron. Exploratory analyses within the meta-analysis suggested similar benefits among patients with MS and SCI, with some outcomes favoring those with incomplete SCI or SCIs below the T7 level. These findings underscore the potential benefit of mirabegron in managing NLUTD symptoms, suggesting a favorable profile for improving bladder capacity and patient quality of life in this specific population. [9]

Background References: [1] Ginsberg DA, Boone TB, Cameron AP, et al. The AUA/SUFU Guideline on Adult Neurogenic Lower Urinary Tract Dysfunction: Diagnosis and Evaluation. J Urol. 2021;206(5):1097-1105. doi:10.1097/JU.0000000000002235
[2] Truzzi JC, de Almeida FG, Sacomani CA, Reis J, Rocha FET. Neurogenic bladder - concepts and treatment recommendations. Int Braz J Urol. 2022;48(2):220-243. doi:10.1590/S1677-5538.IBJU.2021.0098
[3] Blok B, Castro-Diaz D, et al. EAU Guidelines on Neuro-Urology. Updated 2026. Accessed July 2, 2026. https://uroweb.org/guidelines/neuro-urology
[4] Cameron AP. Medical management of neurogenic bladder with oral therapy. Transl Androl Urol. 2016;5(1):51-62. doi:10.3978/j.issn.2223-4683.2015.12.07
[5] Kelleher C, Hakimi Z, Zur R, et al. Efficacy and Tolerability of Mirabegron Compared with Antimuscarinic Monotherapy or Combination Therapies for Overactive Bladder: A Systematic Review and Network Meta-analysis. Eur Urol. 2018;74(3):324-333. doi:10.1016/j.eururo.2018.03.020
[6] Zhang D, Sun F, Yao H, et al. The Efficacy and Safety of Mirabegron for the Treatment of Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review and Meta-analysis. Front Pharmacol. 2021;12:756582. Published 2021 Nov 18. doi:10.3389/fphar.2021.756582
[7] Akkoc Y. Efficacy and safety of mirabegron for treatment of neurogenic detrusor overactivity in adults with spinal cord injury or multiple sclerosis: a systematic review. Spinal Cord. 2022;60(10):854-861. doi:10.1038/s41393-022-00853-3
[8] Zhou Z, Wang X, Li X, Liao L. Detrusor relaxing agents for neurogenic detrusor overactivity: a systematic review, meta-analysis and network meta-analysis. BJU Int. 2024;133(1):25-33. doi:10.1111/bju.16142
[9] Welk B, Krhut J, Sýkora R. An individual participant meta-analysis of mirabegron in multiple sclerosis and spinal cord injury. Neurourol Urodyn. 2024;43(4):803-810. doi:10.1002/nau.25439
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Please summarize national guidelines and clinical trials on the use of mirabegron in neurogenic bladder dysfunction. Can mirabegron be used in patients with spinal cord dysfunction when anticholinergics are contraindicated due to cognitive dysfunction or unacceptable anticholinergic side effects?

Level of evidence

A - Multiple high-quality studies with consistent results  Read more→



Please see Tables 1-5 for your response.


 

The Treatment of Neurogenic Lower Urinary Tract Dysfunction in Persons with Spinal Cord Injury: An Open Label, Pilot Study of Anticholinergic Agent vs. Mirabegron to Evaluate Cognitive Impact and Efficacy

Design

Pre–post intervention

N= 20

Objective

To test whether replacement of oral anticholinergic (AC) agents with mirabegron for neurogenic lower urinary tract dysfunction (NLUTD) yields improved cognitive function in older persons with spinal cord injury (SCI) and to test whether mirabegron is safe and as efficacious as AC. 

Study Groups

All participants (n= 20)

Inclusion Criteria

Both genders with spinal cord injury being treated for neurogenic bladder and age >60 years; taking a minimum regimen of 3 months with AC for bladder control; all ethnic groups; veterans; normal clinical labs for CBC, CMP, and urinalysis (UA) within past 6 months

Exclusion Criteria

Diagnosis of dementia or cognitive impairment from another condition; end-stage renal disease; poorly controlled blood pressure; renal function with serum creatinine >2× normal range; liver function with >2× normal liver enzyme levels; history of cardiac dysrhythmias; concomitant treatment with another AC agent for mood or pain; active/unstable conditions

Methods Participants were first studied on AC at baseline then switched to mirabegron for 6 months. Cognitive tests measured a range of cognitive functions including memory, executive function, and attention. Tests included: (1) Weschler Memory Scale IV (WMS-IV); (2) Saint Louis University Mental Status Exam (SLUMS); (3) The Telephone Executive Assessment Scale (TEXAS); (4) Symbol Digit Modality Test (SDMT); and (5) Stroop Color-Word Test (SCWT). These tests were conducted at 0 months on AC and after 6 months of mirabegron therapy. To ensure comparable efficacy to AC, bladder function assessments (i.e. bladder diary (BD) and Neurogenic Bladder Symptom Score (NBSS) were performed monthly as well. Data on Neurogenic Bladder Symytom Score was collected. After baseline data were collected, participants were started on mirabegron 25 mg daily. After 3 weeks, partici pants were called and queried for any significant adverse changes in BD measures as listed above. If there were any adverse changes in BD measures (e.g. increased FI), the dose was increased to 50 mg daily. After this optimal dosing was determined, participants remained on that mirabegron dose for the remainder of the study (~5 months). 
Duration

6 months

Outcome Measures

Primary: Cognitive tests of executive function (TEXAS, SDMT), attention (SCWT), and memory (SLUMS and WMS-IV Story A/B) Secondary: Efficacy and safety including NBSS, bladder diary, HR, EKG, and MAP

Baseline Characteristics   Age (years) AC agent (daily dose)

Length of time (years) on AC agent

1 65 Oxybutynin (20 mg)

11

2 63 Oxybutynin (15 mg)

4

3 66 Oxybutynin SA (20 mg)

4

4 63 Oxybutynin SA (20 mg)

4

5 66 Oxybutynin SA (10 mg)

18

6 66 Tolterodine SA (2 mg)

10

7 81 Oxybutynin SA (10 mg)

2

8 68 Oxybutynin SA (20 mg)

23

9 75 Oxybutynin (15 mg)

12

10 63 Trospium (40 mg)

6

11 62 Solefenacin (5 mg)

3

12 84 Trospium (40 mg)

3

13 73 Trospium (40 mg)

6

14 78 Oxybutynin (10 mg)

1

15 73 Trospium (20 mg)

3

16 77 Oxybutynin SA (20 mg)

14

17 63 Trospium (40 mg)

4

18 63 Solefenacin (10 mg)

6

19 64 Trospium (40 mg)

1

20 70 Oxybutynin SA (30 mg)

6

Results   V1 (AC) V7 (Mirabegron) p-value
Immediate Story A recall-SLUMS score  --- --- 0.01
Delayed Story A recall- SLUMS score  ---  --- 0.01
Delayed Story B recall- SLUMS score  ---  --- 0.004
TEXAS  ---  --- 0.04
SDMT scores --- --- 0.12

SCWT scores were not significantly different between V1 and V7 on any page (pages 1–3) (p=0.21, 0.18, 0.14, respectively).

NBSS Score: Total incontinence, total storage and voiding, and total consequences showed a statistically significant overall effect of visit (p = 0.01, 0.01, 0.01), with TSV and TC being significantly lower at V7 than V1. 

Bladder diary: Within the BD data, the frequency of incontinence was the only measure that showed a significant effect of visit (p =0.02) and a statis tically significant decrease between V1 (mean rank number 1.50) and V7 (mean rank number 1.15) (p=0.03).

Note: Data presented primarily as graphs

 Adverse Events Heart rate, mean arterial pressure, and EKGs were unchanged
Study Author Conclusions

Older persons with SCI on AC for NLUTD demonstrated improved short-term and delayed memory as well as executive function when switched to mirabegron. Efficacy of mirabegron for NLUTD symptoms was superior to AC with no adverse effects on bowel or cardiovascular function. 

Critique

The study was limited by its small sample size and short duration, which may not fully capture long-term cognitive benefits or potential adverse effects. Additionally, the lack of a control group and reliance on subjective measures for some outcomes may limit the robustness of the findings. 

Table 1 References:
[10] Trbovich M, Romo T, Polk M, et al. The treatment of neurogenic lower urinary tract dysfunction in persons with spinal cord injury: An open label, pilot study of anticholinergic agent vs. mirabegron to evaluate cognitive impact and efficacy. Spinal Cord Ser Cases. 2021;7(1):50. Published 2021 Jun 10. doi:10.1038/s41394-021-00413-6

 

Efficacy and Safety of Mirabegron for the Treatment of Neurogenic Detrusor Overactivity Resulting from Traumatic Spinal Cord Injury: A Prospective Study

Design

Prospective cohort study

N= 30

Objective

To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI).

Study Groups

All patients (n= 30)

Inclusion Criteria

Patients with stable neurological involvement for >3 months, who demonstrated NDO on invasive urodynamic study (UDS), and were on clean intermittent catheterization (CIC)

Exclusion Criteria

Patients with gross hydroureteronephrosis, grade III or greater reflux, symptomatic urinary tract infections, history of intravesical botulinum toxin injection within the past 1 year, prior urological surgery, pelvic radiation, history of glaucoma, uncontrolled hypertension, unstable cardiac disease, abnormal ECG, deranged kidney or liver function tests, and those unwilling to give consent

Methods

For eligible patients, a detailed physical examination including pulse and blood pressure (BP), classification of spinal injury as per International Standards for Neuro-logical Classification of SCI, along with baseline investigations such as urine routine and culture, kidney and liver function tests, electrocardiogram, ultrasound KUB, micturating cysto‐urethrogram. All patients were asked to make a bladder diary of 72 h duration which included time of CIC, volume emptied, time of leak, if any, and fluid intake. An average value for all theparameters recorded on the 3‐day bladder diary wascalculated and used for statistical analysis. Patients were started on Mirabegron 50 mg once daily for 6 weeks. A 3-day bladder diary was made at baseline, followed by a repeat bladder diary and UDS at 6 weeks. Data were analyzed using paired t test. 

Duration

January 2018 to July 2019

Outcome Measures

Primary: Bladder diary parameters, UDS variables

Secondary: Tolerability/side-effect profile

Baseline Characteristics  

All patients (n= 30)

Male

26 (86.7%)

Female

4 (13.3%)

Age

30.07 (18–67 years)

Duration of injury

1.84 (4 months–12 years)

Level of spinal injury - Cervical

5 (16.7%)

Level of spinal injury - Thoracic

24 (80%)

Level of spinal injury - Lumbar

1 (3.3%)

AIS grade - AIS A

8 (26.7%)

AIS grade - AIS B

5 (16.67%)

AIS grade - AIS C

11 (36.6%)

AIS grade - AIS D

6 (20%)

Results   Baseline (n = 30) 6 weeks (n = 30)

p value

Frequency/24 h 6.63 ± 2.2 5.37 ± 0.96

.002

CIC volume (ml) 275.8 ± 108.8 341.5 ± 93.5

.0002

Number of incontinence episodes/24 h 3.97 ± 2.58 2.27 ± 2.75

<.0001

Time between CIC and leakage (h) 1.73 ± 1.15 2.75 ± 1.35

.00001

Cystometric capacity (ml) 348.33 ± 144.11 406.22 ± 137.01

.008

Maximum amplitude of neurogenic detrusor overactivity (NDO) (cm H2O) 54.19 ± 32.73 41.01 ± 25.69

.005

Adverse Events

Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment.

Study Author Conclusions

Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI. 

Critique

The study demonstrated significant improvements in clinical and urodynamic parameters, indicating the efficacy of mirabegron. However, the study's small sample size and lack of a placebo control limit the generalizability of the findings. Additionally, the short duration of 6 weeks does not provide insights into the long-term efficacy and safety of the treatment. 

Table 2 References:
[11] Vasudeva P, Prasad V, Yadav S, et al. Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study. Neurourol Urodyn. 2021;40(2):666-671. doi:10.1002/nau.24604

 

Efficacy and Safety of Mirabegron for the Treatment of Neurogenic Detrusor Overactivity—Prospective, Randomized, Double-blind, Placebo-controlled Study
Design

Prospective, multicenter, randomized, double-blind, placebo-controlled study

N= 78

Objective

To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity (NDO)

Study Groups

Mirabegron 50 mg (Group A, n= 32)

Placebo (Group B, n= 34)

Inclusion Criteria

Patients aged 18-65 years with NDO due to SCI or MS, SCI at least 12 months prior, neurologically stable MS for 6 months, willing to withdraw anticholinergic medications

Exclusion Criteria

NDO from other neurological diseases, indwelling catheters/epicystostomy, onabotulinumtoxin A treatment in the past 12 months, symptomatic urinary tract infections, severe cardiovascular disease

Methods

Patients were randomized to receive either mirabegron 50 mg or placebo for 4 weeks. Urodynamic parameters, 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring adverse events. Changes were assessed using Kruskal-Wallis one-way analysis of variance.

Duration

4 weeks of double-blind treatment period

Outcome Measures

Primary: Change in cystometric capacity

Secondary: Changes in volume at first detrusor contraction, compliance, maximal detrusor pressure, severity of incontinence, patient-reported outcomes, safety variables

Baseline Characteristics   Group A (active treatment) Group B (placebo)
Number of patients (n) 32 34
Male (n) 23 26
Female (n) 9 8
Age (years) 43.46 43.7
BMI 26.33 26.45
Time since SCI/MS diagnosis (years) 10.76 10.33
Previously treated with anticholinergics (n) 28 26
Spinal cord injury patients - SCI (n) 21 28
Traumatic SCI (n) 20 23
Non-traumatic SCI (n) 1 5
MS patients (n) 11 6
Results   Group A (active treatment) Group B (placebo)

A vs B

Cystometric capacity, (mL) 183.5 ± 121.6 210.44 ± 135.34 0.0610
Volume at the first detrusor contraction, (mL) 127 ± 104.72 125.03 ± 81.92 0.0005
Compliance, (mL/1 cmH2O) 34.78 ± 26.65 34.73 ± 22.84 0.0041
Maximal detrusor pressure, (cmH2O) 71.91 ± 10.04 74.91 ± 13.03 0.3173
24-hour pad weight test, (mL) 763.97 ± 1092.7 572.42 ± 792.99 0.0561
Incontinence- Quality of Life 43.92 ± 18.04 43.4 ± 24.27 0.0060
Treatment Satisfaction-Visual Analog Scale  50.43 ± 37.26 37.89 ± 38.18 0.0004
Patient Perception of Bladder Condition 4.06 ± 1.16 4.12 ± 1.32 0.0013
Adverse Events

The incidence of drug-related adverse events was 3.13% in the mirabegron group. No statistically significant changes in safety variables were observed. 

Study Author Conclusions

Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well. 

Critique

The study was well-designed with a prospective, randomized, double-blind, placebo-controlled approach, providing strong evidence for the efficacy and safety of mirabegron. However, the short duration of the active treatment period is a limitation, as it may not fully capture long-term efficacy and safety. Additionally, the small sample size may limit the generalizability of the findings. 



Table 3 References:
[12] Krhut J, Borovika V, Blkov K, et al. Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity-Prospective, randomized, double-blind, placebo-controlled study. Neurourol Urodyn. 2018;37(7):2226-2233. doi:10.1002/nau.23566

Real-World Effects of Mirabegron in Patients with Chronic Neurogenic Detrusor Overactivity – A Retrospective Cohort Study
Design

Retrospective cohort study

N= 63

Objective To investigate the tolerability and the effects of the β-3-adrenoceptor-agonist mirabegron on urinary incontinence and urodynamic parameters in patients with chronic neurogenic detrusor overactivity (NDO)
Study Groups All patients (N= 63)
Inclusion Criteria Patients with chronic (>12 months) NDO (diagnosed based on urodynamic studies)resulting from spinal cord injury (SCI), myelomeningocele (MMC), or multiple sclerosis (MS), who had been prescribed mirabegron
Exclusion Criteria Patients who rejected the use of their health-related data, missing data, non-compliance
Methods The patient database at a SCI rehabilitation center in Switzerland was screened for eligible patients. Data regarding bladder management, urinary incontinence, concurrent medication for NDO, and urodynamic parameters were collected retrospectively. Standard video-urodynamic examinations were performed before and after mirabegron treatment. 
Duration January 2015 to December 2018
Outcome Measures

Primary: Occurrence of urinary incontinence

Secondary: Changes in urodynamic parameters (maximum detrusor pressure, bladder capacity, detrusor compliance)

Baseline Characteristics  

All patients

(N= 63)

Men, n (%) 48 (76.2%)
Lesion level - At T6 or above 36 (57.1%)
Lesion level - Below T6 27 (42.9%)
Injury severity - AIS A 30 (47.6%)
Injury severity - AIS B 13 (20.6%)
Injury severity - AIS C 5 (7.9%)
Injury severity - AIS D 15 (23.8%)
Etiology - SCI 60 (95.2%)

Mirabegron dose

50 mg

25 mg

 

50 (79.4%)

13 (20.6%)

Results  

Pre-Mirabegron

(n=63)

Follow-Up 3 Months

(n=63)

Follow-Up 12 Months

(n=42)

p-value
Incontinence, n (%) 38 (60.3%) 21 (33.3%)* 16 (38.1%)* 0.002
Median max detrusor pressure, cmH2O (95% CI) 35 (29-41) 26 (20-34)* 29.5 (22-40)* 0.04
Median max cystometric capacity, mL (95% CI) 330 (304-400) 440 (370-460)* 420 (370-460)* 0.005
Median detrusor compliance, mL/cmH2O (95% CI) 30 (24-34) 45 (36-68)* 63 (43-91)* 0.0001
*Significant difference vs pre-mirabegron value
Adverse Events No patient discontinued mirabegron due to side effects. Reported side effects included dry skin, tachycardia, headache, and stomach pain. Most patients reporting side effects were also on antimuscarinics
Study Author Conclusions Mirabegron demonstrated a clinically relevant effect and a good safety profile. Concomitant treatment of NDO with mirabegron may allow reduction in the dose of antimuscarinic medication and thus, improve the long-term persistence of NDO treatment.
Critique The study provides valuable real-world data on the effects of mirabegron in patients with chronic NDO, showing significant improvements in urinary incontinence and urodynamic parameters. However, the retrospective design may limit the ability to establish causality and the potential for selection bias exists. The study's findings are relevant for future prospective studies to confirm these results.
Table 4 References:
[13] Krebs J, Pannek J, Rademacher F, Wllner J. Real-World Effects of Mirabegron in Patients with Chronic Neurogenic Detrusor Overactivity - A Retrospective Cohort Study. Res Rep Urol. 2020;12:187-192. Published 2020 May 22. doi:10.2147/RRU.S253713

Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open‐label, phase 3, dose‐titration study
Design

Open-label, multicenter, baseline-controlled, Phase III study

N= 86

Objective To evaluate the efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity (NDO) using clean intermittent catheterization
Study Groups

Children (3 to <12 years) (n= 55)

Adolescents (12 to <18 years) (n= 31)

Inclusion Criteria

Children and adolescents aged 3 to <18 years with NDO confirmed by urodynamic investigation, weight ≥11 kg, CIC for ≥4 weeks before screening, and a current indication for drug therapy to manage NDO

Exclusion Criteria

Other known genitourinary conditions that could cause overactive contractions or incontinence, gastrointestinal problems such as partial or complete obstruction, decreased motility such as paralytic ileus, risk of gastric retention, indwelling catheter less than 4 weeks of screening, and symptomatic UTI

Methods

Participants received once-daily mirabegron at an adult dose equivalent of 25 mg, increased to 50 mg unless there were safety/tolerability concerns. Urodynamic assessments were performed at baseline, Weeks 4 and 24. Other assessments included bladder e-diary, Pediatric Incontinence Questionnaire (PIN-Q), Patient Global Impression of Severity (PGI-S), Clinician Global Impression of Change (CGI-C), and Acceptability questionnaires

Duration

Efficacy treatment period: 24 weeks

Long-term safety period: 52 weeks

Outcome Measures

Primary: Change from baseline to Week 24 in maximum cystometric capacity (MCC)

Baseline Characteristics   Children (3 to <12 years) N = 55 Adolescents (12 to <18 years) N = 31 Total N = 86
Sex, male, n (%) 22 (40.0) 17 (54.8) 39 (45.3)
Mean age, years (SD) 7.9 (2.5) 14.0 (1.7) 10.1 (3.7)
Mean weight, kg (SD) 29.83 (13.41) 50.96 (13.78) 37.45 (16.90)
Mean height, cm (SD) 124.77 (18.69) 152.91 (12.06) 134.91 (21.40)
Mean BMI, kg/m2 (SD) 18.18 (3.94) 21.96 (6.02) 19.55 (5.10)
Mean duration of NDO, years (SD) 5.80 (3.33) 9.44 (5.18) 7.11 (4.43)
Closure of spina bifida, n (%) 43 (78.2) 24 (77.4) 67 (77.9)
Shunt for hydrocephalus, n (%) 23 (41.8) 17 (54.8) 40 (46.5)
Results   Children (3 to <12 years) N = 43 Adolescents (12 to <18 years) N = 25 Total (N = 68)

Maximum cystometric capacity (MCC), mL, change from baseline to Week 24 LOCF 

P-Value, week 24 vs. baseline

 

72.09

< 0.001

 

113.21

< 0.001

 

87.20

< 0.001

       
Adverse Events

Common Adverse Events: Urinary tract infection (23.3%), nasopharyngitis (5.8%), pyrexia (5.8%), constipation (4.7%), respiratory tract infection viral (4.7%), upper respiratory tract infection (4.7%)

Serious Adverse Events: None considered related to treatment

Study Author Conclusions Mirabegron was effective and well-tolerated in the treatment of pediatric patients with NDO.
Critique The study demonstrated significant improvements in urodynamic parameters and was well-tolerated, aligning with adult profiles. However, the lack of a placebo group limits the ability to attribute improvements solely to mirabegron. The open-label design may introduce bias, although objective measures were used. The study's applicability is supported by concordance with patient- and clinician-reported outcomes.
Table 5 References:
[14] Baka-Ostrowska M, Bolong DT, Persu C, et al. Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol Urodyn. 2021;40(6):1490-1499. doi:10.1002/nau.24657