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Sender Herschorn - One of the best experts on this subject based on the ideXlab platform.

  • effect of Mirabegron on cognitive function in elderly patients with overactive bladder moca results from a phase 4 randomized placebo controlled study pillar
    BMC Geriatrics, 2020
    Co-Authors: Tomas L Griebling, Sender Herschorn, David R. Staskin, Noll L Campbell, Jeffrey Mangel, Dina Elsouda, Carol R Schermer
    Abstract:

    Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebo-controlled study (PILLAR; NCT02216214) described the efficacy and safety of Mirabegron, a β3-adrenoreceptor agonist, for treatment of wet OAB in patients aged ≥65 years. This pre-planned analysis aimed to measure differences in cognitive function between Mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA). Outpatients aged ≥65 years with wet OAB were randomized 1:1 to Mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to Mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved. Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the Mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of Mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the Mirabegron group (−0.2 [0.1]) or the placebo group (−0.1 [0.1]). Treatment with Mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo. NCT02216214 (prospectively registered August 13, 2014).

  • long term treatment of older patients with overactive bladder using a combination of Mirabegron and solifenacin a prespecified analysis from the randomized phase iii synergy ii study
    Neurourology and Urodynamics, 2019
    Co-Authors: Elizabeth R Mueller, Sender Herschorn, Christopher R Chapple, Paul Abrams, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon, Salman Alshukri, Tomasz Rechberger
    Abstract:

    AIMS SYNERGY II was a 12-month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of Mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups ( 1 bpm were noted in the combination and Mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy. CONCLUSIONS Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age.

  • long term safety and efficacy of Mirabegron and solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Sender Herschorn, Arwin Ridder, Paul Abrams, Asha Paireddy, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of solifenacin and Mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of solifenacin succinate 5mg plus Mirabegron 50mg tablets (combination treatment) versus solifenacin or Mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; Mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (Mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; Mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to Mirabegron and solifenacin for the number of incontinence episodes (vs Mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p Conclusions Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus Mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or Mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • long term safety and efficacy of Mirabegron and solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Sender Herschorn, Christopher R Chapple, Arwin Ridder, Paul Abrams, Asha Paireddy, Dudley Robinson, Matthias Stoelzel, Rob Van Maanen, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of solifenacin and Mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of solifenacin succinate 5mg plus Mirabegron 50mg tablets (combination treatment) versus solifenacin or Mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; Mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (Mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; Mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to Mirabegron and solifenacin for the number of incontinence episodes (vs Mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p p =0.002) and micturitions (vs Mirabegron: AMD −0.5, 95% CI −0.8 to −0.2, p p =0.004). Conclusions Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus Mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or Mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • cardiovascular safety of the β3 adrenoceptor agonist Mirabegron and the antimuscarinic agent solifenacin in the synergy trial
    The Journal of Clinical Pharmacology, 2018
    Co-Authors: William B White, Sender Herschorn, Jeffrey Frankel, Christopher R Chapple, Arwin Ridder, Asha Paireddy, Christian Gratzke, Dudley Robinson, Matthias Stoelzel, Robert Van Maanen
    Abstract:

    There have been concerns that treatment of overactive bladder with β3 -adrenoceptor agonists may potentially have detrimental cardiovascular (CV) side effects. We evaluated the CV safety of Mirabegron, a β3 -adrenoceptor agonist, alone and in combination therapy with the antimuscarinic agent solifenacin. The SYNERGY trial was a multinational, multicenter, randomized, double-blind, parallel-group, placebo and active-controlled phase 3 trial. Patients were randomized to receive solifenacin 5 mg + Mirabegron 50 mg (combination 5 + 50 mg), solifenacin 5 mg + Mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg monotherapy, Mirabegron 25 mg monotherapy, Mirabegron 50 mg monotherapy, or placebo for a 12-week double-blind treatment period. A total of 3398 patients were included in the study. Mean changes from baseline to the end of therapy in ECG parameters were similar across treatment groups, although there was an increase in heart rate of 1 beat/minute in the Mirabegron treatment groups. There were no clinically meaningful differences in change from baseline in QTcF between monotherapies and placebo and between monotherapies and combination therapy. There were very few major CV events: 1 of 853 (0.1%) with a nonfatal myocardial infarction in the combination 5 + 25 mg group, 2 of 848 (0.2%) with a nonfatal stroke in the combination 5 + 50 mg group, and no events in the other groups. This CV safety analysis of the combination of Mirabegron and solifenacin showed rates of CV events comparable with those for monotherapy treatments based on assessments of vital signs, electrocardiograms, and adjudicated CV events.

Christopher R Chapple - One of the best experts on this subject based on the ideXlab platform.

  • long term treatment of older patients with overactive bladder using a combination of Mirabegron and solifenacin a prespecified analysis from the randomized phase iii synergy ii study
    Neurourology and Urodynamics, 2019
    Co-Authors: Elizabeth R Mueller, Sender Herschorn, Christopher R Chapple, Paul Abrams, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon, Salman Alshukri, Tomasz Rechberger
    Abstract:

    AIMS SYNERGY II was a 12-month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of Mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups ( 1 bpm were noted in the combination and Mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy. CONCLUSIONS Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age.

  • long term safety and efficacy of Mirabegron and solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Sender Herschorn, Christopher R Chapple, Arwin Ridder, Paul Abrams, Asha Paireddy, Dudley Robinson, Matthias Stoelzel, Rob Van Maanen, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of solifenacin and Mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of solifenacin succinate 5mg plus Mirabegron 50mg tablets (combination treatment) versus solifenacin or Mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; Mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (Mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; Mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to Mirabegron and solifenacin for the number of incontinence episodes (vs Mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p p =0.002) and micturitions (vs Mirabegron: AMD −0.5, 95% CI −0.8 to −0.2, p p =0.004). Conclusions Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus Mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or Mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • efficacy and tolerability of Mirabegron compared with antimuscarinic monotherapy or combination therapies for overactive bladder a systematic review and network meta analysis
    European Urology, 2018
    Co-Authors: Con Kelleher, K Maman, Samuel Aballea, Jameel Nazir, Emad Siddiqui, Zalmai Hakimi, Richard Zur, Christopher R Chapple
    Abstract:

    Abstract Background Mirabegron is an established treatment alternative to antimuscarinic therapy for patients with overactive bladder (OAB), as shown by efficacy and tolerability data from phase III trials. Objective To assess efficacy and tolerability of Mirabegron 50mg versus antimuscarinic monotherapies and combination therapies. Design, setting, and participants Systematic literature review and network meta-analysis of randomised controlled trials (2000–2017) assessing eligible treatments for OAB. Outcome measurements and statistical analysis Efficacy assessments included micturition frequency, urgency urinary incontinence, dry rate, and 50% reduction in incontinence. Tolerability assessments included dry mouth, constipation, blurred vision, and hypertension. Results and limitations A total of 64 studies ( n =46 666) were included in the network meta-analysis. Mirabegron 50mg was significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for Mirabegron 50mg versus most active treatments, but solifenacin 10mg monotherapy and solifenacin 5mg plus Mirabegron 25 or 50mg in combination were more efficacious for some/all outcomes. Mirabegron 50mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between Mirabegron 50mg and all treatments (including placebo) for the remaining endpoints. Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints. Conclusions The relief of key OAB symptoms produced by Mirabegron 50mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5mg plus Mirabegron 25 or 50mg appears to provide an efficacy benefit compared with Mirabegron 50mg, with the expected side effects of individual antimuscarinics. Patient summary This study assessed the efficacy and tolerability of different drug treatments for OAB. Mirabegron 50mg was as effective as antimuscarinic therapy, with fewer common, bothersome side effects such as dry mouth, constipation, and urinary retention. Combination treatment of solifenacin 5mg plus Mirabegron 25 or 50mg was more effective than Mirabegron 50mg alone, but with more anticholinergic side effects.

  • cardiovascular safety of the β3 adrenoceptor agonist Mirabegron and the antimuscarinic agent solifenacin in the synergy trial
    The Journal of Clinical Pharmacology, 2018
    Co-Authors: William B White, Sender Herschorn, Jeffrey Frankel, Christopher R Chapple, Arwin Ridder, Asha Paireddy, Christian Gratzke, Dudley Robinson, Matthias Stoelzel, Robert Van Maanen
    Abstract:

    There have been concerns that treatment of overactive bladder with β3 -adrenoceptor agonists may potentially have detrimental cardiovascular (CV) side effects. We evaluated the CV safety of Mirabegron, a β3 -adrenoceptor agonist, alone and in combination therapy with the antimuscarinic agent solifenacin. The SYNERGY trial was a multinational, multicenter, randomized, double-blind, parallel-group, placebo and active-controlled phase 3 trial. Patients were randomized to receive solifenacin 5 mg + Mirabegron 50 mg (combination 5 + 50 mg), solifenacin 5 mg + Mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg monotherapy, Mirabegron 25 mg monotherapy, Mirabegron 50 mg monotherapy, or placebo for a 12-week double-blind treatment period. A total of 3398 patients were included in the study. Mean changes from baseline to the end of therapy in ECG parameters were similar across treatment groups, although there was an increase in heart rate of 1 beat/minute in the Mirabegron treatment groups. There were no clinically meaningful differences in change from baseline in QTcF between monotherapies and placebo and between monotherapies and combination therapy. There were very few major CV events: 1 of 853 (0.1%) with a nonfatal myocardial infarction in the combination 5 + 25 mg group, 2 of 848 (0.2%) with a nonfatal stroke in the combination 5 + 50 mg group, and no events in the other groups. This CV safety analysis of the combination of Mirabegron and solifenacin showed rates of CV events comparable with those for monotherapy treatments based on assessments of vital signs, electrocardiograms, and adjudicated CV events.

  • systematic review and meta analysis on the efficacy and tolerability of Mirabegron for the treatment of storage lower urinary tract symptoms overactive bladder comparison with placebo and tolterodine
    International Journal of Urology, 2018
    Co-Authors: Arcangelo Sebastianelli, Christopher R Chapple, Giorgio Ivan Russo, Steven A Kaplan, Kevin T Mcvary, Ignacio Moncada, Stavros Gravas, Giuseppe Morgia, Sergio Serni, Mauro Gacci
    Abstract:

    A systematic review and meta-analysis was carried out to evaluate the efficacy and safety of Mirabegron 50 mg and 100 mg in the treatment of storage lower urinary tract symptoms/overactive bladder in comparison with a placebo and tolterodine 4 mg. A total of 491 articles were collected and eight randomized studies were identified as eligible for this meta-analysis. Overall, eight trials were included in the meta-analysis evaluating 10 248 patients. Mirabegron at both doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated with the reduction of incontinence episodes per 24 h, reduction of mean number of micturitions per 24 h, increase of voided volume and reduction of urgency episodes per 24 h, compared to a placebo. Both Mirabegron 50 mg and Mirabegron 100 mg were associated with a significant reduction of nocturia episodes when compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more effective than a placebo in the reduction of nocturia episodes. Furthermore, Mirabegron 50 mg showed a slightly, but significantly, better efficacy than tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and Mirabegron 100 mg shared the same risk of overall treatment-emergent adverse events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a significantly greater risk than the placebo. However, Mirabegron 100 mg showed a slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08) and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective treatment for patients with storage lower urinary tract symptoms/overactive bladder, providing a reduction of incontinence, urgency and frequency; an improvement of voided volume with a slight, but statistically, significant improvement of nocturia; with a good safety profile. These findings should be considered for the treatment planning of patients with storage lower urinary tract symptoms/overactive bladder.

Emad Siddiqui - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and tolerability of Mirabegron compared with antimuscarinic monotherapy or combination therapies for overactive bladder a systematic review and network meta analysis
    European Urology, 2018
    Co-Authors: Con Kelleher, K Maman, Samuel Aballea, Jameel Nazir, Emad Siddiqui, Zalmai Hakimi, Richard Zur, Christopher R Chapple
    Abstract:

    Abstract Background Mirabegron is an established treatment alternative to antimuscarinic therapy for patients with overactive bladder (OAB), as shown by efficacy and tolerability data from phase III trials. Objective To assess efficacy and tolerability of Mirabegron 50mg versus antimuscarinic monotherapies and combination therapies. Design, setting, and participants Systematic literature review and network meta-analysis of randomised controlled trials (2000–2017) assessing eligible treatments for OAB. Outcome measurements and statistical analysis Efficacy assessments included micturition frequency, urgency urinary incontinence, dry rate, and 50% reduction in incontinence. Tolerability assessments included dry mouth, constipation, blurred vision, and hypertension. Results and limitations A total of 64 studies ( n =46 666) were included in the network meta-analysis. Mirabegron 50mg was significantly more efficacious than placebo for all efficacy endpoints. Comparable overall efficacy was observed for Mirabegron 50mg versus most active treatments, but solifenacin 10mg monotherapy and solifenacin 5mg plus Mirabegron 25 or 50mg in combination were more efficacious for some/all outcomes. Mirabegron 50mg was significantly better tolerated regarding dry mouth, constipation, and urinary retention than 21/22, 9/20, and 7/10 active comparators, respectively; similar overall tolerability was observed between Mirabegron 50mg and all treatments (including placebo) for the remaining endpoints. Limitations of the study included between-trial variations in the definition of certain endpoints and heterogeneity of the available data (eg, number of studies and patients assessed) for comparator treatments across different endpoints. Conclusions The relief of key OAB symptoms produced by Mirabegron 50mg is significantly better than placebo, and similar to a range of common antimuscarinics, with the benefit of significantly fewer bothersome anticholinergic side effects such as dry mouth. Combination treatment of solifenacin 5mg plus Mirabegron 25 or 50mg appears to provide an efficacy benefit compared with Mirabegron 50mg, with the expected side effects of individual antimuscarinics. Patient summary This study assessed the efficacy and tolerability of different drug treatments for OAB. Mirabegron 50mg was as effective as antimuscarinic therapy, with fewer common, bothersome side effects such as dry mouth, constipation, and urinary retention. Combination treatment of solifenacin 5mg plus Mirabegron 25 or 50mg was more effective than Mirabegron 50mg alone, but with more anticholinergic side effects.

  • The efficacy of Mirabegron in the treatment of urgency and the potential utility of combination therapy
    Therapeutic Advances in Urology, 2018
    Co-Authors: Karlerik Andersson, Emad Siddiqui, Moses Huang, Nurul Choudhury, Jean-nicolas Cornu, Cees Korstanje, Philip Van Kerrebroeck
    Abstract:

    Urgency is the prevalent and most bothersome symptom of overactive bladder (OAB) and the treatment of urgency is the primary objective in the management of OAB. Urgency has a major impact on other symptoms of OAB and culminates in an increased frequency of micturition and reduced volume voided, which may contribute to shorter intervals between the need to void. Antimuscarinic agents and Mirabegron, a β3-adrenoceptor agonist, constitute the main oral pharmacotherapeutic options for the treatment of urgency and other OAB symptoms. The reduction of urgency and other OAB symptoms significantly improve health-related quality of life. This review will explore the distinct mechanisms of action and effects of antimuscarinic agents and Mirabegron, in relation to their effect on the pathophysiology of urgency. The review will also provide an overview of the various validated measurements of urgency and the numerous clinical trials regarding antimuscarinic agent monotherapy, Mirabegron monotherapy, or combination treatment with Mirabegron added on to the antimuscarinic agent solifenacin. A narrative review of the literature relating to pathophysiology of urgency, the validated measurements of urgency, and clinical trials relating to the pharmacological treatment of urgency. Antimuscarinic agent monotherapy, Mirabegron monotherapy, or combination treatment with Mirabegron added on to the antimuscarinic agent solifenacin statistically significantly reduce the symptoms of urgency compared with placebo. Combination therapy with Mirabegron added on to solifenacin also statistically significantly reduces the symptoms of severe urgency compared with antimuscarinic agent monotherapy. A critique of the clinical benefits of combination therapy is also provided. Combination therapy provides an alternative treatment in patients with OAB that includes urgency who respond poorly to first-line monotherapy and who may otherwise often move on to more invasive treatments.

  • persistence and adherence with Mirabegron versus antimuscarinic agents in patients with overactive bladder a retrospective observational study in uk clinical practice
    European Urology, 2017
    Co-Authors: Christopher R Chapple, Jameel Nazir, Emad Siddiqui, Zalmai Hakimi, Florent Guelfucci, Amine Khemiri, Francis Fatoye, Sally Bowditch, Adrian Wagg
    Abstract:

    Abstract Background Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for Mirabegron, a β 3 -adrenoceptor agonist with a different adverse event profile. Objective To compare persistence and adherence with Mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period. Design, setting, and participants Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database. Eligibility: age ≥18 yr, ≥1 prescription for target OAB drug (between May 1, 2013 and June 29, 2014), and 12-mo continuous enrolment before and after the index prescription date. Interventions Mirabegron, darifenacin, fesoterodine, flavoxate, oxybutynin ER or immediate-release (IR), propiverine, solifenacin, tolterodine ER or IR, and trospium chloride. Outcome measurements and statistical analysis The primary endpoint was persistence (time to discontinuation). Secondary endpoints included 12-mo persistence rates and adherence (assessed using medication possession ratio, MPR). Cox proportional-hazards regression models and logistic regression models adjusted for potential confounding factors were used to compare cohorts. Analyses were repeated after 1:1 matching. Results and limitations The study population included 21996 eligible patients. In the unmatched analysis, the median time-to-discontinuation was significantly longer for Mirabegron (169 d, interquartile range [IQR] 41–not reached) compared to tolterodine ER (56 d, IQR 28–254; adjusted hazard ratio [HR] 1.55, 95% confidence interval 1.41–1.71; p p Conclusions Persistence and adherence were statistically significantly greater with Mirabegron than with tolterodine ER and other antimuscarinics prescribed for OAB in the UK. Patient summary This study assessed persistence and adherence (or compliance) with medications prescribed for OAB in a large UK population. We found that patients prescribed Mirabegron remained on treatment for longer and showed greater adherence than those prescribed traditional antimuscarinics.

  • Mirabegron for the treatment of overactive bladder a review of efficacy safety and tolerability with a focus on male elderly and antimuscarinic poor responder populations and patients with oab in asia
    Expert Review of Clinical Pharmacology, 2017
    Co-Authors: Christopher R Chapple, Emad Siddiqui
    Abstract:

    ABSTRACTIntroduction: Mirabegron is established as an alternative monotherapy to antimuscarinics for the treatment of overactive bladder (OAB) symptoms. Initial studies focused on Western populations, but over the past few years other populations and subpopulations have been evaluated.Areas covered: The authors’ knowledge of the literature was used to develop the manuscript alongside a PubMed search (‘Mirabegron and clinical trial’ and ‘overactive bladder’) to select independent studies of Mirabegron. Up-to-date information is provided about the most recent Mirabegron clinical trial and real-world efficacy, safety and tolerability data in a variety of patient populations with OAB, including those from different geographic areas, men, the elderly, and those with poor tolerability to antimuscarinics.Expert commentary: Improvements in efficacy parameters in patients with OAB at Mirabegron doses approved for clinical use (25 and 50 mg/day) are also associated with clinically meaningful benefits according to p...

  • efficacy and safety of Mirabegron add on therapy to solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4 week solifenacin monotherapy a randomised double blind multicentre phase 3b study beside
    European Urology, 2016
    Co-Authors: Marcus J Drake, Sender Herschorn, Javier Cambronero, Adil Esen, Stavros Athanasiou, David Mitcheson, Tahir Saleem, Moses Huang, Emad Siddiqui
    Abstract:

    Background Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. Objective To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and Mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg. Design, setting, and participants OAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on Mirabegron 25mg increasing to 50mg after week 4. Outcome measurements and statistical analysis The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus Mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy. Results and limitations A total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p Conclusions Adding Mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg. Patient summary In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with Mirabegron 50mg. Combining Mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. Trial registration ClinicalTrials.gov NCT01908829.

Carol R Schermer - One of the best experts on this subject based on the ideXlab platform.

  • effect of Mirabegron on cognitive function in elderly patients with overactive bladder moca results from a phase 4 randomized placebo controlled study pillar
    BMC Geriatrics, 2020
    Co-Authors: Tomas L Griebling, Sender Herschorn, David R. Staskin, Noll L Campbell, Jeffrey Mangel, Dina Elsouda, Carol R Schermer
    Abstract:

    Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebo-controlled study (PILLAR; NCT02216214) described the efficacy and safety of Mirabegron, a β3-adrenoreceptor agonist, for treatment of wet OAB in patients aged ≥65 years. This pre-planned analysis aimed to measure differences in cognitive function between Mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA). Outpatients aged ≥65 years with wet OAB were randomized 1:1 to Mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to Mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved. Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the Mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of Mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the Mirabegron group (−0.2 [0.1]) or the placebo group (−0.1 [0.1]). Treatment with Mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo. NCT02216214 (prospectively registered August 13, 2014).

  • patient reported outcomes in patients with overactive bladder treated with Mirabegron and tolterodine in a prospective double blind randomized two period crossover multicenter study prefer
    Health and Quality of Life Outcomes, 2018
    Co-Authors: Sender Herschorn, David R. Staskin, Jonathan Fialkov, Terry Walsh, Katherine Gooch, Carol R Schermer
    Abstract:

    The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with Mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment. PREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naive adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and Mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90. In total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), Mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with Mirabegron than tolterodine ER. On average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with Mirabegron or tolterodine ER. However, during Mirabegron treatment, patients were more likely to achieve clinically relevant improvements in tolerability and HRQoL (as measured by the MID for the OAB-q or an OAB-S Medication Tolerability score ≥ 90) than during tolterodine ER treatment. NCT02138747 ; registered May 13, 2014.

  • a prospective double blind randomized two period crossover multicenter study to evaluate tolerability and patient preference between Mirabegron and tolterodine in patients with overactive bladder prefer study
    International Urogynecology Journal, 2018
    Co-Authors: David R. Staskin, Sender Herschorn, Jonathan Fialkov, Terry Walsh, Carol R Schermer
    Abstract:

    The objective of this study was to assess the tolerability and treatment preference in patients with overactive bladder (OAB) treated with Mirabegron or tolterodine. This was a two-period, 8-week crossover, double-blind, phase IV study (PREFER; NCT02138747) in treatment-naive adults with OAB for 3 months or longer randomized to one of four treatment sequences in a 5:5:1:1 ratio (Mirabegron/tolterodine, tolterodine/Mirabegron, Mirabegron/Mirabegron, or tolterodine/tolterodine), separated by a washout period of 2 weeks. The primary endpoint was drug tolerability using the Medication Tolerability scale of the OAB Treatment Satisfaction (OAB-S) questionnaire at end of treatment (EoT). Period-by-treatment interactions were analyzed to determine any effect of drug order. Patient preference, change from baseline in OAB symptoms, and treatment-emergent adverse events (TEAEs) were assessed. A total of 358 randomized patients completed the OAB-S Medication Tolerability scale questionnaire at one or more visits after the baseline evaluation. The mean (95% CI) OAB-S Medication Tolerability scores were significantly higher (better tolerability) for Mirabegron (86.29 [83.50, 89.08]) than for tolterodine (83.40 [80.59, 86.20]; p = 0.004). The period-by-treatment interaction was not significant (p = 0.955). Improvements in OAB-S Medication Tolerability scores at EoT were more evident in women, patients aged ≥65 years, and in patients without baseline incontinence, and were greater with Mirabegron than with tolterodine extended release. There were no significant differences in patient preference or improvements in OAB symptoms. Significant differences in favor of Mirabegron were observed for anticholinergic TEAEs (20.4% vs. 27.4%; p = 0.042) and specifically for gastrointestinal disorders (14.7% vs. 22.5%; p = 0.015). Tolerability of Mirabegron was significantly higher than that of tolterodine, and patient preference and improvements in OAB symptoms were comparable. Both treatments were well tolerated; however, anticholinergic side effects were higher with tolterodine.

Dudley Robinson - One of the best experts on this subject based on the ideXlab platform.

  • long term treatment of older patients with overactive bladder using a combination of Mirabegron and solifenacin a prespecified analysis from the randomized phase iii synergy ii study
    Neurourology and Urodynamics, 2019
    Co-Authors: Elizabeth R Mueller, Sender Herschorn, Christopher R Chapple, Paul Abrams, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon, Salman Alshukri, Tomasz Rechberger
    Abstract:

    AIMS SYNERGY II was a 12-month phase III trial in patients with overactive bladder (OAB) symptoms that investigated the safety and efficacy of the combination of Mirabegron and solifenacin in comparison with each monotherapy. This analysis evaluated the trial findings using four age subgroups ( 1 bpm were noted in the combination and Mirabegron younger age groups only. No clinically significant findings were observed in the other safety parameters. The efficacy variables improved with all treatments and the greatest improvements were typically observed with combination therapy. CONCLUSIONS Mirabegron and solifenacin combination therapy was a well-tolerated and effective treatment for patients with OAB symptoms irrespective of their age.

  • long term safety and efficacy of Mirabegron and solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Sender Herschorn, Arwin Ridder, Paul Abrams, Asha Paireddy, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of solifenacin and Mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of solifenacin succinate 5mg plus Mirabegron 50mg tablets (combination treatment) versus solifenacin or Mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; Mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (Mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; Mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to Mirabegron and solifenacin for the number of incontinence episodes (vs Mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p Conclusions Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus Mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or Mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • long term safety and efficacy of Mirabegron and solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Sender Herschorn, Christopher R Chapple, Arwin Ridder, Paul Abrams, Asha Paireddy, Dudley Robinson, Matthias Stoelzel, Rob Van Maanen, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of solifenacin and Mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of solifenacin succinate 5mg plus Mirabegron 50mg tablets (combination treatment) versus solifenacin or Mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; Mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (Mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; Mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to Mirabegron and solifenacin for the number of incontinence episodes (vs Mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p p =0.002) and micturitions (vs Mirabegron: AMD −0.5, 95% CI −0.8 to −0.2, p p =0.004). Conclusions Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus Mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or Mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • cardiovascular safety of the β3 adrenoceptor agonist Mirabegron and the antimuscarinic agent solifenacin in the synergy trial
    The Journal of Clinical Pharmacology, 2018
    Co-Authors: William B White, Sender Herschorn, Jeffrey Frankel, Christopher R Chapple, Arwin Ridder, Asha Paireddy, Christian Gratzke, Dudley Robinson, Matthias Stoelzel, Robert Van Maanen
    Abstract:

    There have been concerns that treatment of overactive bladder with β3 -adrenoceptor agonists may potentially have detrimental cardiovascular (CV) side effects. We evaluated the CV safety of Mirabegron, a β3 -adrenoceptor agonist, alone and in combination therapy with the antimuscarinic agent solifenacin. The SYNERGY trial was a multinational, multicenter, randomized, double-blind, parallel-group, placebo and active-controlled phase 3 trial. Patients were randomized to receive solifenacin 5 mg + Mirabegron 50 mg (combination 5 + 50 mg), solifenacin 5 mg + Mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg monotherapy, Mirabegron 25 mg monotherapy, Mirabegron 50 mg monotherapy, or placebo for a 12-week double-blind treatment period. A total of 3398 patients were included in the study. Mean changes from baseline to the end of therapy in ECG parameters were similar across treatment groups, although there was an increase in heart rate of 1 beat/minute in the Mirabegron treatment groups. There were no clinically meaningful differences in change from baseline in QTcF between monotherapies and placebo and between monotherapies and combination therapy. There were very few major CV events: 1 of 853 (0.1%) with a nonfatal myocardial infarction in the combination 5 + 25 mg group, 2 of 848 (0.2%) with a nonfatal stroke in the combination 5 + 50 mg group, and no events in the other groups. This CV safety analysis of the combination of Mirabegron and solifenacin showed rates of CV events comparable with those for monotherapy treatments based on assessments of vital signs, electrocardiograms, and adjudicated CV events.

  • patient reported outcomes from synergy a randomized double blind multicenter study evaluating combinations of Mirabegron and solifenacin compared with monotherapy and placebo in oab patients
    Neurourology and Urodynamics, 2018
    Co-Authors: Dudley Robinson, David R. Staskin, Arwin Ridder, Asha Paireddy, Matthias Stoelzel, Con Kelleher, Elizabeth R Mueller, Christian Falconer, Jianye Wang, Rob Van Maanen
    Abstract:

    Aims To evaluate patient-reported outcomes (PROs) of combinations of solifenacin and Mirabegron compared with solifenacin and Mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial. Methods Following a 4-week placebo run-in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + Mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + Mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, Mirabegron 25 mg, Mirabegron 50 mg or placebo for 12 weeks, followed by a 2-week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB-q Symptom Bother score, health-related quality of life (HRQOL) Total score, treatment satisfaction-visual analogue scale (TS-VAS), and patient perception of bladder condition (PPBC) questionnaires. Results Overall, 3527 patients were randomized into the study, with 3494 receiving double-blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB-q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB-q Symptom Bother score responder rates at EoT were statistically significantly higher versus Mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups. Conclusions PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB-q Symptom Bother score, HRQOL Total score, and PPBC.