Pharmacological Management of Urinary Incontinence: Current and Emerging Treatment

Introduction and Hypothesis: Patients with overactive bladder (OAB) often undergo prolonged treatment with one or more oral OAB medications. OnabotulinumtoxinA (onabotA), a type A botulinum toxin, may provide an appropriate alternative to oral treatments in patients intolerant of or refractory to one or more oral OAB medications. The GRACE study demonstrated realworld benefits of onabotA treatment for OAB in patients refractory to oral medications. This exploratory post hoc analysis of data from the GRACE study aims to determine if treatment history impacts benefit from treatment with onabotA. Methods: This is a subanalysis of the GRACE study, a prospective observational study (NCT02161159) that enrolled patients with symptomatic OAB inadequately managed by at least one oral OAB medication. Patients had a treatment history of one or more anticholinergics (AC) and/or β-3 adrenoreceptor agonists (β-3) for relief of OAB; results were stratified according to treatment history. Patients in this analysis elected to discontinue oral medications upon treatment with onabotA. Safety was followed for 12 months in all patients that received at least 1 dose of onabotA; efficacy was determined over a 12-week period.Results: Compared to baseline levels, significant reductions in urinary incontinence (UI), urgency, micturition, and nocturia were noted as early as 1 week and were sustained at 12 weeks, regardless of the type and number of oral medications taken before treatment with onabotA. At 12 weeks post-onabotA, the mean change from baseline UI episodes/day for those with a treatment history of only one AC was −2.4 (n = 43, p ≤ 0.001); more than one AC, −2.4 (n = 52, p ≤ 0.001); one β-3, −3.3 (n = 12, p < 0.05); at least one AC

Section: Discussionmentioning

confidence: 99%

One treatment with onabotulinumtoxinA relieves symptoms of overactive bladder in patients refractory to one or more oral medications

Farrelly

Hamid

Lorenzo-Gómez

et al. 2023

“…For example, antimuscarinic (anticholinergic) drugs block muscarinic receptors on the detrusor thereby inhibiting bladder contraction and improving UUI 5,24 and several, such as tolterodine, fesoterodine, trospium, solifenacin, and darifenacin, have proven efficacy in treating UUI 24 . Patient adherence, however, tends to be poor given that anticholinergic drugs have dry mouth, constipation, somnolence, drowsiness and blurred vision as adverse effects, 11,28 and prolonged use has been associated with a risk of dementia in elderly patients 29,30 . The beta‐3‐adrenoceptor agonist mirabegron, which is better tolerated than anticholinergic drugs with a comparable overall efficacy, acts to induce detrusor relaxation 11 but may affect the cardiovascular system and has pharmacokinetic interactions with other drugs 31,32 .…”

Section: Standard Treatmentsmentioning

confidence: 99%

“…Novel antimuscarinics are being developed with the hope of retaining the efficacy demonstrated by standard treatments while reducing the number and severity of side effects. 28 The review specifically discussed imidafenacin, which has an efficacy comparable to tolterodine and other antimuscarinics but a milder side effect profile that may improve patient adherence to treatment, and tarafenacin, which versus placebo in a Phase 2 trial demonstrated an improvement in overactive bladder symptoms but a higher rate of dry mouth than other antimuscarinics. 28 DA‐8010 is another recent antimuscarinic agent recently evaluated against both solifenacin and placebo in a Phase 2 trial in patients with overactive bladder symptoms.…”

Section: Emerging Treatmentsmentioning

confidence: 99%

“… 28 The review specifically discussed imidafenacin, which has an efficacy comparable to tolterodine and other antimuscarinics but a milder side effect profile that may improve patient adherence to treatment, and tarafenacin, which versus placebo in a Phase 2 trial demonstrated an improvement in overactive bladder symptoms but a higher rate of dry mouth than other antimuscarinics. 28 DA‐8010 is another recent antimuscarinic agent recently evaluated against both solifenacin and placebo in a Phase 2 trial in patients with overactive bladder symptoms. The results suggested that both the 2.5 and 5 mg doses had efficacies comparable to solifenacin while the 2.5 mg dose had fewer adverse drug reactions.…”

Section: Emerging Treatmentsmentioning

confidence: 99%

“…While novel beta‐3‐adrenoreceptor agonizts continue being developed, 28 the most recently developed compound, vibegron, was approved by the FDA in 2020. 50 This development program, consisting of two Phase 3 trials preceding approval, found that vibegron reduced micturition frequency, urgency episodes, and urgency incontinence with statistical significance compared to placebo 51 , 52 and had a favorable safety profile with a smaller percentage of patients discontinuing treatment due to adverse events compared to the tolterodine 51 or imidafenacin 52 control groups.…”

Section: Emerging Treatmentsmentioning

confidence: 99%

See 2 more Smart Citations

Mixed urinary incontinence: Are there effective treatments?

Gamé

Dmochowski

Robinson

2022

The aim of this debate article is to discuss whether effective treatments are available for mixed urinary incontinence (MUI). Because patients with MUI have both stress and urgency urinary incontinence (SUI and UUI) episodes and current treatment guidelines currently recommend treating the predominant symptom first, this article presents standard and emerging treatments for both SUI and UUI before discussing how well these treatments meet the medical needs of patients with MUI. Standard treatments presented include noninvasive options such as lifestyle changes and pelvic floor exercises, pharmacological agents, and surgery. Treatment of all three types of urinary incontinence (UI) is usually initiated with noninvasive options, after which treatment options diverge based on UI subtype. Multiple pharmacological agents have been developed for the treatment of UUI and overactive bladder, whereas surgery remains the standard option for SUI and stress-predominant MUI. The divide between UUI and SUI options seems to be propagated in emerging treatments, with most novel pharmacological agents still targeting UUI and even having SUI and stress-predominant MUI as exclusion criteria for participation in clinical trials. Considering that current treatment options focus almost exclusively on treating the predominant symptom of MUI and that emerging pharmacological treatments exclude patients with stresspredominant MUI during the development phase, effective treatments for MUI are lacking both in standard and emerging practice. Ideally, agents with dual mechanisms of action could provide symptom benefit for both the stress and urgency components of MUI.

Improvement of medication adherence for desmopressin by adjusting the prescription dosage in male patients with overactive bladder: A claims database analysis

Tsubouchi,

Maeda,

Emoto

et al. 2024

ObjectivesDesmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence.MethodsPatients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan–Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin.ResultsThe study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high‐adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC.ConclusionDesmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.