Hypothesis / aims of study
Intra-detrusor Botulinum Toxin A (BTX-A) is an effective treatment for neurogenic detrusor overactivity. There is extensive published evidence advocating BTX-A treatment for children with spinal dysraphism (Spina Bifida(SB)), and for neurogenic detrusor overactivity in adults with multiple sclerosis and spinal cord injury. However, little evidence has been reported for BTX-A treatment in adults with SB.
This study aims to report on the long-term clinical outcomes of intradetrusor BTX-A in adult patients with Spina Bifida. The primary endpoint was to evaluate patient satisfaction with BTX-A treatment. Secondary endpoints included quality of life effect and durability of treatment.
Study design, materials and methods
We retrospectively analysed the clinical records of all patients with SB at a large neurosciences centre in London, and those who had been treated with intra-detrusor BTX-A were identified. Demographic, clinical, quality of life and urodynamic data were acquired. Urodynamic assessment was performed pre-BTX, and follow up UDS when feasible.
We identified 152 adult patients with SB, mean age 26 years (range 18-47), 82 males:70 females. 17 (11%) patients had received BTX-A treatment from this cohort, of which 3 were ambulant (16%) and the remainder were wheelchair bound. The first treatment round was at a mean of 11 years (4 to19) ago, with a mean of 6 rounds of treatment per patient (1-13). This totals 89 individual treatment rounds of BTX. The majority of the earlier treatment rounds 53/89 (59%) were using Dysport (mean dose 1000U), and the remainder with onabotulinumtoxinA (mean dose 250U). 5/17 (29%) had started off BTX treatment during childhood or adolescence and continued into adulthood.
All patients were taking an antimuscarinic when receiving BTX-A, and 13 (76%) were performing Clean Intermittent Self Catheterisation (CISC) prior to BTX and all continued this after treatment. 10 (58%) of patients had some previous reconstructive urinary tract and bowel surgery (mitrofanoff:3, augmentation cystoplasty:2, suprapubic catheter:1, rectus sheath sling:1, artificial urinary sphincter:2, ACE channel:3).
On pre-treatment urodynamics the mean bladder capacity pre-BTX was 350mls (200 to 480), 13 (76%) exhibited detrusor overactivity, 11 (64%) patients exhibited loss of compliance, 4 (24%) patients had concomitant stress urinary incontinence, 7 (41%) had recurrent urinary tract infections (UTIs), and 5 (29%) had vesicoureteric reflux also requiring treatment.
Despite BTX-A treatment, 5 (29%) patients discontinued repeat treatment due to inefficacy or worsened UTIs, 2 (12%) patients went onto have augmentation cystoplasty (1 with bladder neck closure), 1 (6%) ileal conduit, 1 (6%) renal transplantation and 1 is awaiting urinary diversion.
Patient self-reported satisfaction with intradetrusor BTX-A treatment is 1.5/3 suggesting mild to moderate benefit on a simple Likert scale. Mean ICIQ-OAB scores pre and 3 months post the latest BTX was 6.8 and 4.1 respectively, with bother score improving from 17.8 to 8.6.
Interpretation of results
The bladder dysfunction occurring with SB is complex and requires long-term evaluation and management, a significant proportion of which may be at risk of eventual renal compromise. The disability varies according to the severity of the dysraphism which produces a range of patterns of bladder dysfunction requiring a range of combinations of treatment modalities. Our population of patients demonstrate this complexity, with patients demonstrating numerous urodynamic abnormalities and a significant proportion undergoing urological reconstructive surgery in the natural history of the condition.
The majority of patients (73%) had repeated BTX-A injections, with 29% having started their treatment rounds during adolescence, and one third eventually discontinuing due to need for escalated treatment. 76% of this cohort performed CISC routinely and a high proportion reporting recurrent UTI. BTX-A was also given to patients for loss of compliance, in the absence of detrusor overactivity. Patient self-reported satisfaction demonstrates improved symptom scores using the ICIQ-OAB and bother scores and a simple Likert score but due to the range of concomitant urodynamic abnormalities do not completely address all the issues. For the majority of patients BTX-A in this cohort has been safe and satisfactory as a treatment and well tolerated in its delivery.
Although the majority of patients found the BTX-A treatment effective, 5 (29%) went on to have reconstructive urological surgery. Further data is needed to form conclusive evidence of predictors of outcome and alternatives for BTX-A treatment in adults with SB.
This is a very complex group of patients, some with multiple urodynamic abnormalities. This study attempts to examine long-term durability of BTX treatment with a mean follow-up of 11 years. This study identifies competing factors in this group that may lead to discontinuation of BTX-A. Such factors include loss of compliance, recurrent UTI, vesicoureteric reflux, stress urinary incontinence which may need a combination of additional treatments.
14/17 (82%) of patients elected to have more than 1 round of BTX-A, with positive self-reported satisfaction noted and improvement in QOL scores. Long-term 5 (29%) discontinued BTX-A treatment to address other competing urodynamic complaints.