RESUMEN
AIMS: In studies utilizing a 20-injection-site paradigm of onabotulinumtoxinA treatment for overactive bladder (OAB), some patients performed clean intermittent catheterization (CIC). An alternative injection paradigm of fewer injections targeting the lower bladder may reduce the need for CIC by maintaining upper bladder function. This study evaluated the efficacy and safety of an unapproved alternative 10-injection-site paradigm targeting the lower bladder. METHODS: In this phase 4, double-blind, parallel-group study, patients with OAB and urinary incontinence (UI) for ≥6 months with ≥3 episodes of urinary urgency incontinence (no more than 1 UI-free day) and ≥8 micturitions per day over 3 days during screening were randomized 2:1 to onabotulinumtoxinA 100 U or placebo injected at 10 sites in the lower bladder. RESULTS: Of 120 patients, 78 in the onabotulinumtoxinA group and 39 in the placebo group had efficacy assessments. In the double-blind phase, mean change from baseline at week 12 in daily frequency of UI episodes was greater with onabotulinumtoxinA (-2.9) versus placebo (-0.3) (least squares mean difference [LSMD]: -2.99, p < 0.0001). Achievement of 100% (odds ratio [OR]: 6.15 [95% confidence interval, CI: 0.75-50.37]), ≥75% (OR: 7.25 [2.00-26.29]), and ≥50% improvement (OR: 4.79 [1.87-12.28]) from baseline in UI episodes was greater with onabotulinumtoxinA versus placebo. Reductions from baseline in the daily average number of micturitions (LSMD: -2.24, p < 0.0001), nocturia (LSMD: -0.71, p = 0.0004), and urgency (LSMD: -2.56, p < 0.0001) were greater with onabotulinumtoxinA than with placebo. Treatment benefit was improved or greatly improved in the onabotulinumtoxinA group (74.0% of patients) versus placebo (17.6%) (OR: 13.03 [95% CI: 3.23-52.57]). Mean change from baseline in Incontinence Quality of Life score was greater with onabotulinumtoxinA versus placebo (LSMD: 24.2, p = 0.0012). Two of 78 (2.6%) patients in the onabotulinumtoxinA group used CIC during the double-blind period; no females used CIC during the double-blind period. Commonly reported adverse events (≥5%) were urinary tract infection (UTI), dysuria, and productive cough for both groups; rate of UTI was higher with onabotulinumtoxinA versus placebo. CONCLUSION: In patients treated with onabotulinumtoxinA for OAB with UI, an unapproved alternative injection paradigm targeting the lower bladder demonstrated efficacy over placebo, with a low incidence of CIC.
Asunto(s)
Toxinas Botulínicas Tipo A , Vejiga Urinaria Hiperactiva , Incontinencia Urinaria , Infecciones Urinarias , Humanos , Toxinas Botulínicas Tipo A/efectos adversos , Calidad de Vida , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Infecciones Urinarias/etiología , Método Doble CiegoRESUMEN
Overactive bladder is a common and distressing problem. Standard therapy is directed towards modifying the detrusor motor sensitivity and response via anticholinergic medication. Currently available medications are reviewed and alternative targets for treatment are presented.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Músculo Liso/efectos de los fármacos , Incontinencia Urinaria/tratamiento farmacológico , Acetilcolina/metabolismo , Aminas/farmacología , Aminas/uso terapéutico , Animales , Anticonvulsivantes/farmacología , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Cresoles/farmacología , Cresoles/uso terapéutico , Ácidos Ciclohexanocarboxílicos/farmacología , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Evaluación Preclínica de Medicamentos , Gabapentina , Humanos , Ácidos Mandélicos/farmacología , Ácidos Mandélicos/uso terapéutico , Antagonistas Muscarínicos/farmacología , Músculo Liso/inervación , Músculo Liso/metabolismo , Fenilpropanolamina/farmacología , Fenilpropanolamina/uso terapéutico , Vigilancia de Productos Comercializados , Quinuclidinas/farmacología , Quinuclidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor Muscarínico M3/antagonistas & inhibidores , Receptor Muscarínico M3/metabolismo , Succinato de Solifenacina , Tetrahidroisoquinolinas/farmacología , Tetrahidroisoquinolinas/uso terapéutico , Tartrato de Tolterodina , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/inervación , Vejiga Urinaria/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
This paper outlines the evaluation and management of neurogenic vesicourethral dysfunction (NVUD). The anatomy and neurophysiology involved with lower urinary tract functions are reviewed. Multiple sclerosis, diabetes, lumbar disc prolapse, and Parkinson's disease are specifically addressed. Proper evaluation of patients suspected of having NVUD, which is fundamental to making an accurate diagnosis, is discussed. This is followed by options for initiating individualized management plans that focus on protecting and preserving renal function, in addition to relieving the symptoms of NVUD.