Botulinum toxin A: First-line therapy for idiopathic detrusor overactivity

We are well aware that overactive bladder (OAB) is extremely common. The most recent Canadian bladder survey by Herschorn and colleagues demonstrated that OAB symptoms were present in 13.1% of men and 14.7 % of women across Canada.1 In addition, it has been shown to have a tremendous impact on a patient’s quality of life, similar to that experienced by someone with diabetes or rheumatoid arthritis.2,3 Unfortunately, the effectiveness of current OAB treatment protocols in alleviating patient symptoms are not adequate, which is why investigators are looking at new agents, such as BTX A. Currently, there are over 10 different anticholinergic medications on the Canadian market for OAB. The most commonly prescribed medication for this condition, oxybutynin, is fraught with potential problems. The FDA, in 2007, released a warning; this medication is to be used with caution in the elderly and children and common side effects are hallucinations, confusion and cognitive changes.4 Others researchers, such as Kay and colleagues, have documented the potential for serious cognitive decline with this medication.5 As a result, urologists have switched to treating OAB with newer medications to avoid these neurological sequelae. The drawback with these new medications, unfortunately, still revolves around side effects and, ultimately, patient compliance. The significant side effects of dry mouth and constipation, as well as poor patient perceived benefit in symptom reduction, have resulted in extremely poor medication adherence rates. Sears and colleagues examined anti-cholinergic medication compliance in a health care system in which medication was given free to patients; the study demonstrated an adherence rate of only 34%.6 This is similar to earlier research by Shaya and colleagues, which demonstrated only a 32 % adherence rate.7 Secondary to these significant side effects and poor patient compliance, investigators have searched for a better alternative for treating OAB. Urologists were already familiar with BTX A, having used it in a variety of other urologic disorders, such as ureteral stent colic,8 interstitial cystitis,9,10 prostatitis10 and benign prostatic hyperplasia.10,11 As data emerged regarding its effectiveness to treat neurogenic detrusor overactivity,12 it was only natural to consider its use to treat non-neurogenic detrusor overactivity (OAB). Many urologists believe it is a matter of time before BTX A becomes an integral cog in the treatment algorithim for OAB. This change in treatment strategy is fuelled by the inability of the current treatment regimen, primarily anticholinergics, to adequately alleviate symptoms in OAB patients. Current work has established the effectiveness of BTX A in OAB. Sahia and colleagues,13 in a randomized, double-blind placebo control study, demonstrated statistically significant increases in cystometric capacity and reduced frequency, urgency urinary incontinence and urgency with the injection of 200 units of BTX A. The beneficial effects were maintained for at least 24 weeks which, incidentally, is longer than most people stay on anticholinergic medication. Others researchers have demonstrated similar statistically significant amelioration of symptoms with BTX A.14–16 However, with any “new” procedure, patient safety is always extremely important. Detractors of the use of BTX A will express concern regarding urinary retention, urinary tract infections (UTIs), hematuria, distant muscle weakness, as well as the invasiveness of the procedure. There is no doubt that these are legitimate concerns if, in fact, they are truly relevant. It has been clearly demonstrated that BTX A can easily and comfortably be given under local anesthetic in the cystoscopy suite in a matter of minutes with minimal discomfort to the patient and with minimal side effects.17 Hematuria does occur, but to date there is not a single case report of an individual requiring a blood transfusion post-BTX A injection. Urinary tract infections do occur16,18 in the setting of BTX A injection, but there is no data demonstrating an increased risk over cystoscopy alone. Distant muscle weakness has definitely been described with BTX A injections. However, the frequency is extremely low (about 20 reported cases in the literature).18 None of these cases required any intervention and all reports were described in patients with neurogenic detrusor overactivity. Secondary to the small incidence (less than 1%), the association and causation of BTX A in precipitating these events has not been well-established.18 What has been well-established is the risk of urinary retention with BTX A injections.13–16,18 The risk has been shown to be dramatically diminished with decreasing doses of BTX A.19 However, even for individuals who were unfortunate enough to go into retention, researchers have demonstrated that, in properly counselled individuals, quality of life still markedly improved versus before the procedure.20 In fact, quality of life has been extensively studied with regards to BTX A, and, not surprisingly, patients are extremely satisfied with the procedure. A recent study by Sahai and colleagues used the Kings Health Questionnaire (KHQ), which included the following subdomains to measure quality of life: “incontinence impact,” “emotions,” “physical limitations,” “social limitations” and “severity measures.” These subdomains significantly improved in patients who received BTX-A compared with placebo.21 Drug costs in the Canadian health care system will always be a major obstacle. Determining the cost-effectiveness of an intervention, therefore, is a critical undertaking and is more informative than a strict comparison of drug costs. Wu and colleagues assessed the cost-effectiveness of BTX A versus anticholinergic medications for idiopathic urge incontinence.22 The authors discovered that BTX A was much more cost-effective per year than anticholinergic medication. In fact, for anticholinergics to more cost-effective than BTX A injections, the compliance with anticholinergics would have to exceed 75%. Alternatively, the injection costs would have to more than double. The final area of concern for opponents of BTX A involves the possibility of damage to the bladder mucosa with repeated injections every 6 to 9 months. Although the data on this topic are not as robust as that on amelioration of symptoms and quality of life, they are still reassuring. Apostolidis and colleagues biopsied the injection sites and found that BTX A did not appear to be producing significant inflammatory changes, fibrosis or dysplastic changes in urothelium.23 Digesting this plethora of information obviously begs the question: should BTX A be used as a first-line treatment for patients suffering from non-neurogenic detrusor overactivity? Do we continue to use inferior agents with serious significant side effects, poor patient compliance and low success rates? I and others would suggest that the usefulness and success of BTX A make it an excellent candidate to supplant anticholinergics as first-line treatment for OAB. In fact, a recent European Consensus panel reviewed the literature concerning BTX A in the management of neurogenic and non-neurogenic detrusor overactivity; the panel gave a Grade A recommendation to BTX A that it was a safe and effective.24 There are still a few issues that require clarification, most notably the appropriate dose that balances side effects with symptom benefits. Current research places this dose between 100 and 150 units.19 Dose notwithstanding, the age of BTX A for OAB is upon us. Perhaps it is time to stop delaying the inevitable and take the step into the 21st century instead of continuing with old treatment regimens fraught with poor compliance, intolerable side effects and poor cost-effectiveness.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.