Dose escalation improves therapeutic outcome: post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence

<p>Abstract</p> <p>Background</p> <p>Flexible dosing of anticholinergics used for overactive bladder (OAB) treatment is a useful strategy in clinical practice for achieving a maximum effective and maximum tolerated level of therapeutic benefit. In this post hoc analysis we evaluated the efficacy and tolerability of trospium chloride treatment for urinary urge incontinence (UUI) with focus on flexible dosing.</p> <p>Methods</p> <p>The data came from a 12-week, randomised, double-blind, phase IIIb study in which 1658 patients with urinary frequency plus urge incontinence received trospium chloride 15 mg TID (n = 828) or 2.5 mg oxybutynin hydrochloride TID (n = 830). After four weeks, daily doses were doubled and not readjusted in 29.2% (242/828) of patients in the trospium group, and in 23.3% (193/830) in the oxybuytnin group, until the end of treatment. We assessed the absolute reduction in weekly UUI episodes and the change in intensity of dry mouth, recorded in patients' micturition diaries. Adverse events were also evaluated. Statistics were descriptive.</p> <p>Results</p> <p>Dose escalation of either trospium or oxybutynin increased reduction in UUI episodes in the population studied. At study end, there were no relevant differences between the "dose adjustment" subgroups and the respective "no dose adjustment" subgroups (trospium: <it>P </it>= 0.249; oxybutynin: <it>P </it>= 0.349). After dose escalation, worsening of dry mouth was higher in both dose adjusted subgroups compared to the respective "no dose adjustment" subgroups (<it>P </it>< 0.001). Worsening of dry mouth was lower in the trospium groups than in the oxybutynin groups (<it>P </it>< 0.001). Adverse events were increased in the dose adjusted subgroups.</p> <p>Conclusions</p> <p>Flexible dosing of trospium was proven to be as effective, but better tolerated as the officially approved adjusted dose of oxybutynin.</p> <p>Trial registration (parent study)</p> <p>The study was registered with the German Federal Institute for Drugs and Medical Devices (BfArM, Berlin, Germany), registration number 4022383, as required at the time point of planning this study.</p

Can incontinence be cured? A systematic review of cure rates

Background Incontinence constitutes a major health problem affecting millions of people worldwide. The present study aims to assess cure rates from treating urinary (UI) or fecal incontinence (FI) and the number of people who may remain dependent on containment strategies. Methods Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and PEDro were searched from January 2005 to June 2015. Supplementary searches included conference abstracts and trials registers (2013–2015). Included studies had patients ≥ 18 years with UI or FI, reported treatment cure or success rates, had ≥ 50 patients treated with any intervention recognized in international guideline algorithms, a follow-up ≥ 3 months, and were published from 2005 onwards. Title and abstract screening, full paper screening, data extraction and risk-of-bias assessment were performed independently by two reviewers. Disagreements were resolved through discussion or referral to a third reviewer where necessary. A narrative summary of included studies is presented. Results Most evidence was found for UI: Surgical interventions for stress UI showed a median cure rate of 82.3% (interquartile range (IQR), 72–89.5%); people with urgency UI were mostly treated using medications (median cure rate for antimuscarinics = 49%; IQR, 35.6–58%). Pelvic floor muscle training and bulking agents showed lower cure rates for UI. Sacral neuromodulation for FI had a median cure rate of 38.6% (IQR, 35.6–40.6%). Conclusions Many individuals were not cured and hence may continue to rely on containment. No studies were found assessing success of containment strategies. There was a lack of data in the disabled and in those with neurological diseases, in the elderly and those with cognitive impairment. Surgical interventions were effective for stress UI. Other interventions for UI and FI showed lower cure rates. Many individuals are likely to be reliant on containment strategies