Thursday June 11 2009
Botox was injected into the bladder wall
Botox could help “millions of middle-aged Britons” with weak bladders, the Daily Mail reported. According to the newspaper, doctors found that an injection of the toxin directly into the bladder wall can improve symptoms in the over-50s, reducing incontinence and making a “significant” impact on their quality of life. It said that those given the injection reported that they slept better, had more energy and could go out more and become involved in relationships.
The newspaper story is based on a trial in 34 people with weak bladders. This is the second time this trial has been reported. The previous analysis of the results found that the treatment improved bladder capacity, and this latest study reported improvements in the patients’ quality of life.
The patients who were given Botox had tried other treatments for weak bladder and found them unsuccessful. As such, the Botox treatment may only be suitable for those who have not benefited from simpler treatments. Longer-term results and safety were not studied in this trial.
Where did the story come from?
The research was carried out by Dr Arun Sahai and colleagues from the Department of Urology at Guy’s Hospital and King’s College London School of Medicine. All authors are investigators for Allergan Ltd, who provided free Botulinum toxin-A for use in the study. The study was peer reviewed and published in the British Journal of Urology.
What kind of scientific study was this?
This was a randomised controlled trial (RCT). Between May 2004 and February 2006, the researchers recruited 34 men and women, with an average age of 50, who had idiopathic detrusor overactivity (IDO), a form of overactive bladder (OAB). This condition can result in occasional loss of bladder control (incontinence) and is usually treated with lifestyle modification, bladder training and drugs called anticholinergics. This present study used data from a previous 2007 trial that reported the bladder measurements.
To be included in this trial, IDO sufferers must not have been taking anticholinergic therapy before the trial, either because of the side effects of these drugs or because the drugs had not worked when previously tried.
The researchers randomly allocated 16 of the participants to receive 200U of Botox-A and the other 18 to receive a placebo injection of salt water. The injections were delivered using a flexible cystoscope, a minimally invasive procedure in which 20 separate doses of 10U of Botox-A were injected at various points in the bladder. Participants were discharged on the same day, providing they were well enough, and were allowed to use anticholinergic treatments at any time during the trial.
The participants completed three questionnaires on their quality of life, once at the beginning of the study and then at four and 12 weeks after the Botox injections. These included the Incontinence Impact Questionnaire (IIQ-7), the Urogenital Distress Inventory (UDI-6) and the researchers’ own validated version, the King’s Health Questionnaire (KHQ). The KHQ had sub-domains that recorded the patients' experience and perception of specific aspects of their experience, such as the impact of any incontinence, their emotions and physical limitations. Changes in these sub-domains were assessed over the study period.
In the previous trial, reported in 2007, the researchers measured changes in maximum bladder capacity and the amount of urine left in the bladder after emptying. They also measured other pressures and volumes linked to the condition. In the 2007 trial, patients treated with Botox-A experienced significant increases in their maximum bladder capacity after four weeks, compared with those given the placebo.
The blinded part of this current quality-of-life study, where researchers and participants were not aware of the treatment allocation, ran for 12 weeks. After this time, the participants were told which group they had been allocated to. A further follow-up of the Botox-A group occurred at 24 weeks.
What were the results of the study?
The results from the KHQ showed that the participants reported a reduction in the physical impact of incontinence at 12 weeks, which made them feel more confident. No improvement was noted in the placebo group.
In the blinded part of the study, overall quality of life, tested with the KHQ, significantly improved in the Botox-A patients, compared with those who had the placebo, at four and eight weeks. Six out of 10 scores in the KHQ sub-domains of quality of life (for incontinence impact, emotions, physical limitations, social limitations and severity measures) also significantly improved in those who received Botox-A.
In the follow-up, unblinded part of the study (from 12 weeks), the researchers say the benefits of Botox-A lasted for at least 24 weeks and the scores for some domains improved during this time. For example, the scores for ‘role limitations’ were significantly better at 12 weeks than at the beginning of the study, compared to placebo. Further improvement at 24 weeks suggests a slight delay in the improvement for this area. The ‘sleep/energy’ domain was not statistically different in the blinded part of the study but was significantly better at 24 weeks in the extension study.
Six patients in the Botox-A group took anticholinergics at the start of the study, and five of them were able to stop taking them during the trial. This compares to 11 patients taking anticholinergics in the placebo group, none of whom stopped taking the drugs in the part of the study before unblinding. In the Botox-A group, four patients were prescribed anticholinergics by month four and seven patients were prescribed them by month six to further improve symptoms.
What interpretations did the researchers draw from these results?
The researchers concluded that, for 24 weeks, the Botox-A bladder injections improved the quality of life in patients with overactive bladder symptoms that had been difficult to control with anticholinergics.
They also noted that there were improvements in clinical outcomes, but that the improvement in quality of life may be more important for the patient.
What does the NHS Knowledge Service make of this study?
This is the first study to report on the quality-of-life results from an RCT of Botox-A. The effectiveness of Botox-A has been suggested in previous open label trials and these results may work towards ensuring the wider use of this treatment in practice. It is worth noting that the treatment is only suitable for those who have found no benefit from simpler treatments. Other limitations the authors note are:
- The small size of the trial makes finding non-significant results more likely than if more patients had been recruited.
- The free use of anticholinergics by those enrolled in the trial may have reduced the size of any effect as those in the placebo group seemed to need more of this additional treatment. The researchers justify this by saying that stopping or re-instating anticholinergics dependent on patient symptoms was similar to everyday clinical practice and, therefore, this option was made available to the patients.
- Some of the patients who had a greater amount of urine left in the bladder after emptying (post-void residual) required clean intermittent self-catheterisation for a while after the procedure, and developed symptomatic urinary tract infection.
Overall, this is a well-designed and well-conducted study. It demonstrates, under the conditions of a randomised controlled trial, that selected patients benefited from Botox-A for up to 12 weeks after being treated and, in an open label trial, for up to 24 weeks. Long-term safety and optimum dosing were not addressed by this trial.