Hypothesis / aims of study
Neurogenic diseases, particularly spinal cord injury (SCI), cause neurogenic lower urinary tract dysfunction. Suprasacral SCI is most commonly associated with neurogenic detrusor overactivity, which frequently leads to elevated detrusor storage and voiding pressures. These represent a risk for the upper urinary tract. In order to protect the upper urinary tract, antimuscarinic treatment represents the first-line therapy. However, antimuscarinic treatment is frequently abandoned as a result of intolerable side effects (e.g. dry mouth, constipation, blurred vision) or insufficient effectiveness. For these patients, botulinum toxin injections into the detrusor represent an alternative treatment. The effect of botulinum toxin injections and the feasibility of repeated injections has been shown. However, there is a lack of data regarding the long-term effectiveness of the treatment.
The aim of this study was therefore to investigate the long-term effectiveness and treatment adherence of botulinum toxin injections into the detrusor muscle.
Study design, materials and methods
In a retrospective chart analysis at a tertiary reference centre for SCI, we have evaluated patients with long-term Botulinum toxin A therapy. Patients were identified in the register regarding off-label Botulinum toxin A injections into the detrusor performed between 2001 and 2011 before authorization. Patients with Botulinum toxin A injections into the urinary sphincter were excluded.
Results of urodynamic studies before and approx. 6 weeks after injections were collected and analyzed. A successful injection was defined as follows: bladder capacity of ≥400 ml, compliance of ≥20ml/cmH2O and detrusor pressure <40 cmH2O in patients using clean intermittent catheterization (CIC). In patients with a suprapubic catheter (SPC), a successful injection needed to result in urinary continence. In addition to urodynamic parameters, reasons why the treatment had been discontinued were collected.
Descriptive statistics were used to analyze the collected data.
Results
Data from 142 patients (51 women, 91 men) with neurogenic detrusor overactivity were analyzed. In the majority (127/89.4%) detrusor overactivity was the result of spinal cord injury (SCI).
The first Botulinum toxin A injection had taken place a median 2.2 years (lower/upper quartile 0.7/10.4 years) after diagnosis of SCI or another neurologic disease. A dosage of 300 IU was mostly used for the first (92.3%) and last injections (79.0%).
At the time of the first injection 197 (75.4%) patients used CIC, 5 reflex micturition or abdominal pressure and 9 a SPC for bladder evacuation. After the last injection, 89.4% used CIC.
In 91 (64.1%) patients, the Botulinum toxin A treatment was discontinued due to the following reasons: 49 (53.8%) insufficient effect, 17 (18.7%) unknown, 13 (14.3%) no further indication (sufficient oral treatment), 5 (5.5%) patient's wish (e.g. wish to discontinue CIC), 3 (3.3%) costs not covered, 2 (2.2%) side effects (e.g. infections) and 2 (2.2%) bladder wall damage.
Botulinum toxin A treatment was continued in 34 (23.9%) patients over a median time of 14.7 years (lower/upper quartile 9.5/16.9 years). A median of 11 injections (lower/upper quartile 7.0/16.25 injections) had been performed. The median compliance after the last injection was 42 ml/cmH2O (lower/upper quartile 32.5 / 57.5 ml/cmH2O). Four patients had a compliance <20 cmH2O. Ten of these 34 patients had died during the follow-up observation period.
In the remaining 17 (12.0%) patients, no information was available whether Botulinum toxin A injections were continued or discontinued.
Interpretation of results
The results show long-term effectiveness. However, there is also a high discontinuation rate. Loss of effectiveness has been observed in over 50% of the patients. Antibody formation or neurological changes may be the reasons for the reduced response to the treatment.