Presentation Authors: Matthias Walter*, Andrea L. Ramirez, Amanda H.X. Lee, Thomas E. Nightingale, Daniel Rapoport, Alex Kavanagh, Andrei V. Krassioukov, Vancouver, Canada
Introduction: Neurogenic detrusor overactivity (NDO) is a leading trigger of autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). Antimuscarinics, such as fesoterodine, has been shown to improve lower urinary tract (LUT) function. However, the capacity of antimuscarinics to reduce AD in patients with SCI has not been investigated yet.
Methods: Our ethics board approved this prospective, open-label phase II study to quantitatively assess the efficacy of fesoterodine to ameliorate AD during urodynamics (UDS) and in daily life, i.e. 24-hour ambulatory-blood-pressure-monitoring (24-h ABPM). Patients with a chronic (â‰¥1-year), traumatic SCI at or above the level of spinal segment T6, suffering from AD and NDO, underwent UDS and 24-h ABPM at baseline and before the end of the 12-week treatment period (i.e. week 11 and 12). In addition, we assessed the patients&[prime] quality of life (QoL) related to incontinence using the I-QoL questionnaire. Since fesoterodine could potentially affect cognitive and bowel function negatively, we monitored both using the Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score.
Results: Analyses of the first ten patients, who completed the study so far, revealed that fesoterodine objectively improved LUT function compared to baseline, i.e. increased maximum cystometric capacity (247Â±187 vs. 472Â±200mL, p=0.003) and decreased maximum detrusor pressure during bladder filling (52Â±33 vs. 20Â±13cmH2O, p=0.011). Overall, NDO and AD during UDS were eliminated in four individuals. Thus, fesoterodine reduced the severity of AD [i.e. change in systolic BP (Î´SBP) 38Â±19 vs. 26Â±18mmHg]. Furthermore, frequency (24Â±16 vs. 10Â±10, p=0.009) and severity (Î´SBP 57Â±27 vs 42Â±18mmHg) of AD in daily life (i.e. 24-h ABPM) was reduced. In addition, patients&[prime] incontinence-related QoL was improved (I-QoL total score: 72±25 vs. 85Â±22, p=0.028). Neither cognitive (MoCA, 28Â±2 vs. 29Â±1, p=0.588) nor bowel (NBD, 11Â±5 vs. 11Â±6, p=0.914) function deteriorated during treatment.
Conclusions: Our interim analyses suggest that fesoterodine has the capacity to ameliorate AD as well as to improve LUT function and incontinence-related QoL without affecting cognitive or bowel function negatively.
Source of Funding: M. Walter is a 2017 Michael Smith Foundation for Health Research Trainee Award recipient, co-funded with the Rick Hansen Foundation. Pfizer Canada provided a Grant-in-aid including the study drug for this study.