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.

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.

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.

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.

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.

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.