OnabotulinumtoxinA ameliorates autonomic dysreflexia while improving lower urinary tract function and quality of life in individuals with spinal cord injury

Walter M1, Kran S L1, Nigro M K2, Stothers L2, Rapaport D2, Kavanagh A2, Krassioukov A V1

Research Type

Clinical

Abstract Category

Neurourology

Abstract 41
Neurogenic Bladder
Scientific Podium Short Oral Session 4
Wednesday 29th August 2018
11:45 - 11:52
Hall A
Quality of Life (QoL) Spinal Cord Injury Detrusor Overactivity Prospective Study Questionnaire
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
M

Matthias Walter

Links

Abstract

Hypothesis / aims of study
Management of neurogenic lower urinary tract dysfunction is among the highest priorities for individuals with spinal
cord injury (SCI). Neurogenic detrusor overactivity (NDO) not only results in urinary incontinence but is also a risk factor for urinary tract infection (UTI) and long-term renal dysfunction. 

Furthermore, it is a leading cause of sudden increases in systolic blood pressure (BP), i.e. autonomic dysreflexia (AD). The latter 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]

Both NDO and AD combine to place a tremendous burden on individuals with SCI. We hypothesize that by treating NDO, thereby reducing the frequency and severity of AD, quality of life (QoL) in this population can be improved.
Study design, materials and methods
This is a prospective, open-label study to assess the efficacy of onabotulinumtoxinA to reduce AD in individuals following SCI. The University of British Columbia Research Ethics Boards approved this study. This study has been registered at clinicaltrials.gov (NCT02298660). 

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 one month post-treatment (#2).

All individuals underwent intradetrusor onabotulinumtoxinA injections (200 IU) to treat NDO. Assessments included urodynamics, 24-hour ambulatory blood pressure (BP) monitoring and two validated, standardized questionnaires, i.e. incontinence QoL (I-QoL) and AD health-related QoL (AD HR QoL). The I-QoL comprise 22 items over three domains, i.e. avoidance and limiting behaviour (ALB), psychosocial impacts (PSI) and social embarrassment (SE). Each item can have a value on a 5-point scale from 1 (extremely) to 5 (not at all). The AD HR QoL utilizes symptoms characteristics of AD to subjectively score frequency and severity of AD episodes on a daily basis and upon bladder filling. Changes in BP and heart rate were recorded during urodynamic investigations to capture artificially induced AD. The 24-hour ambulatory BP monitoring was applied to detect spontaneous episodes of AD. 

Complications post-treatment were monitored and documented using the Clavien-Dindo (CD) classification of surgical complications.
Results
Overall, 35 individuals (Table 1) completed this study. 

Objectively, onabotulinumtoxinA improved lower urinary tract function resulting in an increased cystometric capacity (from 339±217 to 519±212mL, p<0.001). Thus, onabotulinumtoxinA decreased maximum detrusor pressure during bladder filling (from 46±27 to 17±10cmH2O, p=0.018). Moreover, onabotulinumtoxinA reduced severity of artificially induced AD during UDS#2 (ΔSBP from 48±25 to 35±30mmHg, p=0.008) as well as frequency (from 15±12 to 10±9, p=0.02) and severity (ΔSBP from 60±31 to 42±18mmHg, p<0.001) of spontaneous AD in daily life (ABPM#2). 

Subjectively, a significant (p<0.001) improvement in incontinence-related QoL one month post-treatment was seen across all three domains, i.e. ALB (from 26±7 to 32±6), PSI (from 29±10 to 37±9), SE (from 14±6 to 18±6), and total (from 68±21 to 86±20) compared to baseline assessment. Frequency of AD on a daily basis (from 12±5 to 8±5, p<0.001) and upon bladder filling (from 11±5 to 7±6, p<0.001) as well as severity of AD on a daily basis (from 8±4 to 6±5, p=0.02) and upon bladder filling (from 8±5 to 5±5, p<0.001) were significantly decreased one month post-treatment.  

Only minor complications, i.e. CD I or II occurred in 20 or 6 participants, respectively.
Interpretation of results
Our data supports that onabotulinumtoxinA significantly ameliorates AD (i.e. during UDS and in daily life) in individuals with SCI. Thus, onabotulinumtoxinA not only is a successfull second-line NDO treatment option but provides a substantial capacity to reduces AD-related long-term cardiovascular consequences in individuals living with spinal cord injury.
Concluding message
OnabotulinumtoxinA not only reduces the frequency and severity of AD safely but also improves QoL for individuals living with SCI significantly.
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). The Rick Hansen Institute and the Canadian Foundation for Innovation supperted this study. Allergan provided a Grant-in-aid for this study including the study drug. Clinical Trial Yes Registration Number www.clinicaltrials.gov (NCT02298660) RCT No Subjects Human Ethics Committee The University of British Columbia Research Ethics Boards approved this study. Helsinki Yes Informed Consent Yes