This 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, while this latest study reported improvements in the patients’ quality of life. The patients given this treatment had tried other treatments for weak bladder and found them unsuccessful. As such, the Botox treatment may only be considered suitable for those who have found no benefit 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 the Botulinum toxin-A free 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 years with 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 (BTX-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 BTX-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. This 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 patient experience and perception about the 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 increasesin their maximum bladder capacity after four weeks, compared with 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 the 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 one of the quality of life questionnaires, the KHQ, showed that the participants reported a reduction in the physical impact of incontinence, from 100 to 65 at 12 weeks, leaving the participants 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 patients treated in the Botox A patients compared to those who had the placebo at four and eight weeks. Six out of ten scores in the KHQ sub-domains of quality of life also significantly improved (incontinence impact, emotions, physical limitations, social limitations and severity measures) in those who received BTX-A compared with placebo.

In the follow up unblinded part of the study (from 12 weeks), the researchers say benefits of Botox-A lasted for at least 24 weeks, and some improved during this time. For example the scores for ‘Role Limitations’ became significantly better at 12 weeks compared to placebo with significantly better scores than at the beginning of the study. Further improvement at 24 weeks suggests a slight delay in the improvement for this. The ‘Sleep/Energy’ domain was not statistically different in the blinded part of the study, but it was significantly better at 24 weeks in the extension study.

There were six patients in the Botox A group who were taking anticholinergics at the start of the study, five of whom were able to stop taking them. This compares to eleven patients taking anticholinergics in the placebo group, none of whom could stop taking the drugs in the part of the study before unblinding. In the Botox A group, four patients were prescribed anticholinergics by four months and seven patients were prescribed them by six months 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 anticholinergics for at least 24 weeks.

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 (postvoid 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.