Fesoterodine reduces autonomic dysreflexia in individuals spinal cord injury with neurogenic detrusor overactivity

Walter M1, Ramirez A L1, Lee A H X L1, Rapaport D2, Kavanagh A2, Krassioukov A V1

Research Type

Clinical

Abstract Category

Neurourology

Abstract 511
Open Discussion ePosters
Scientific Open Discussion Session 28
Friday 31st August 2018
13:00 - 13:05 (ePoster Station 2)
Exhibition Hall
Detrusor Overactivity Pharmacology Spinal Cord Injury Prospective Study Quality of Life (QoL)
1. International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, Canada, 2. Department of Urologic Sciences, University of British Columbia, Vancouver, Canada
Presenter
Links

Poster

Abstract

Hypothesis / aims of study
Neurogenic detrusor overactivity (NDO), a leading cause of autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI), can be treated using muscarinic antagonists, e.g. fesoterodine. However, no studies have quantitatively assessed the capacity of fesoterodine to reduce AD, defined is defined according to the International Standards to document remaining Autonomic Function after SCI as an increase in SBP ≥20mmHg from baseline due to a noxious or innocuous stimuli from below the level of injury.[1] Thus, our aim was to investigate the efficacy of fesoterodine to improve lower urinary tract function and ameliorate AD in individuals with SCI.
Study design, materials and methods
This is a prospective, open-label phase II study to quantitatively assess the efficacy of fesoterodine to ameliorate AD during urodynamics (UDS) and daily life, i.e. 24-hour ambulatory-blood-pressure-monitoring (ABPM). 

Individuals following SCI with confirmed AD and NDO were enrolled. The University of British Columbia Research Ethics Boards (H15-02364) and Health Canada (control number 205857) approved this study. This study has been registered at clinicaltrials.gov (NCT02676154). Individuals with chronic (1-year post injury), traumatic SCI at or above the level of spinal segment T6 suffering from AD and NDO following SCI were assessed at baseline (i.e. screening for eligibility, #1) and during treatment (i.e. between 10 to 12 weeks after start of fesoterodine).

Assessment included objective (i.e. UDS and 24-hour ABPM) and subjective (i.e. questionnaires) measures. For the latter, individuals reported incontinence-related quality of life (QoL) using the I-QoL questionnaire. Severity and Frequency of AD-related symptoms were assessed using the AD health related QoL (AD HR-QoL) questionnaire.

As fesoterodine could potentially affect cognitive and bowel function negatively, we monitored both using the Montreal Cognitive Assessment (MoCA) Scale and Neurogenic Bowel Dysfunction (NBD) score.
Results
Analyses of the first seven individuals (Table 1), who completed the study so far revealed that fesoterodine objectively reduced severity of artificially induced AD during UDS#2 (ΔSBP from 34±15 to 25±16mmHg) overall, while AD was eliminated in two individuals. In addition, frequency (from 23±20 to 6±5,p=0.034) and severity (ΔSBP from 53±31 to 34±11mmHg) of spontaneous AD in daily life (ABPM#2) was reduced as well.

Subjectively, fesoterodine not only improved incontinence-related QoL (I-QoL: from 74±24 to 81±27) but also reduced the severity and frequency of AD-related symptoms in three (bladder related) and five (on a daily basis) individuals. 
Cognitive (MoCA, from 28±3 to 29±1) and bowel (NBD score, from 10±4 to 10±5) function did not deteriorate during treatment. Five individuals reported adverse events (all grade 1) judged as related or possibly related to fesoterodine.

Furthermore, fesoterodine objectively improved lower urinary tract function resulting in an increased maximum cystometric capacity (from 311±211 to 581±158mL, p=0.018) and volume at first NDO (from 159±85 to 302±98mL). Thus, fesoterodine decreased maximum detrusor pressure during bladder filling (from 58±37 to 13±11cmH2O, p=0.018), while NDO was eliminated in four individuals.
Interpretation of results
Interim data from our first seven individuals who completed the study supports that fesoterodine can ameliorate AD during UDS and in daily life in this population without affecting cognitive or bowel function negatively. 
Therefore, fesoterodine not only serves as a successful first-line NDO treatment option but as a novel approach to reduce long-term NDO-related cardiovascular consequences in individuals living with spinal cord injury.
Concluding message
Fesoterodine ameliorates AD, while improving LUT function and incontinence-related QoL in individuals with spinal cord injury suffering from NDO without affecting cognitive or bowel function negatively.
Figure 1
References
  1. Krassioukov A, Biering-Sorensen F, Donovan W, et al. International standards to document remaining autonomic function after spinal cord injury. The journal of spinal cord medicine 2012;35(4):201-10.
Disclosures
Funding Michael Smith Foundation for Health Research (MSFHR) and Rick Hansen Foundation (RHF) supported Matthias Walter as a postdoctoral research trainee for this study (Grant ID 17110). Pfizer Canada provided a Grant-in-aid for this study including the study drug. Clinical Trial Yes Registration Number ClinicalTrials.gov Identifier: NCT02676154 RCT No Subjects Human Ethics Committee The University of British Columbia Research Ethics Boards (H15-02364) and Health Canada (control number 205857) approved this study. Helsinki Yes Informed Consent Yes
10/10/2024 00:32:06