Allergan's BOTOX® Receives A Positive Opinion in Fourteen European Countries for Urinary Incontinence in Patients with MS or Spinal Cord Injury
BOTOX® injections can provide long-lasting bladder control for patients with neurogenic bladder
Between 60-80% of people with multiple sclerosis (MS)2,3 and 75-80% of people with spinal cord injury (SCI) will suffer from some degree of bladder dysfunction including urinary incontinence which can be distressing2-4. Urinary incontinence in patients with MS or SCI is frequently caused by a condition called neurogenic detrusor overactivity (NDO), which results in involuntary contractions of the bladder during the filling stage when the bladder should be relaxed. This overactivity can lead to urinary incontinence (uncontrolled urinary leaking). Targeted injections of BOTOX® into the bladder muscle have been shown to reduce the involuntary contractions and increase bladder capacity5,6. In turn, this reduces the number of urinary leaking episodes and may even stop leaking altogether in some patients1.
"We are pleased that BOTOX® has received a positive opinion following
the Mutual Recognition Procedure for the treatment of urinary
incontinence in people living with multiple sclerosis or spinal cord
DIGNITY: The largest clinical trial programme in neurogenic detrusor overactivity
The DIGNITY programme (Double-blind InvestiGation of purified Neurotoxin complex In neurogenic deTrusor overactivitY) was Allergan's phase III clinical programme evaluating the safety and efficacy of BOTOX® as a treatment in patients suffering from urinary incontinence due to neurogenic detrusor overactivity. The programme consisted of two pivotal trials involving nearly 700 patients with either spinal cord injury or multiple sclerosis who were not adequately managed with at least one anticholinergic therapy. Eligible patients needed to be willing to perform clean intermittent catheterisation (CIC) to remove urine from the body, if required.
Patients were randomised to receive a physician-administered single treatment of placebo, 200 or 300 Units of BOTOX® injected as one procedure into the detrusor muscle using a rigid or flexible cystoscope. Treatment was shown to be effective within 2 weeks and lasted for approximately 8-10 months.
The results from the DIGNITY programme showed there was a significant reduction in frequency of urinary incontinence (leakage) reported in BOTOX® treated patients compared to placebo.1
- Patients treated with 200 Units of BOTOX® experienced a highly statistically significant and clinically relevant reduction in the episodes of the most bothersome symptom, urinary incontinence (leakage), at week 6 compared to placebo. In fact, patients treated with 200 Units of BOTOX® experienced a reduction in the number of wetting episodes from 32.4 episodes/week at baseline to only 11.1 episodes / week by week 6 (a reduction of 21.3 episodes). In contrast, patients treated with placebo had an average of 31.5 episodes/week at baseline which was reduced to 21.0 episodes/week by week 6 (a reduction of only 10.5 episodes) (p<0.001)1
- Nearly 40% of patients (37%) treated with 200 Units of BOTOX® were completely dry throughout week 6 compared to just 9% of patients treated with placebo1
- Patients in the BOTOX® treatment groups experienced significant improvements in quality of life including less avoidance behaviour, less psychosocial impact and less embarrassment compared to those on the placebo treatment arm1
Like all medicines, BOTOX® can cause side effects, although not everybody gets them. In general, side effects occur within the first few days following injection. They usually last only for a short time, but they may last for several months and in rare cases, longer. Overall, BOTOX® treatment was generally well-tolerated in the majority of patients in the phase III clinical trial programme. The most common adverse reactions were mainly associated with the urinary tract and included urinary tract infections and the inability to empty the bladder (urinary retention) in patients who were not using a catheter to remove urine1. Other side effects included difficulty in sleeping (insomnia), constipation, muscle weakness, muscle spasm, blood in the urine after the injection, painful urination after the injection, bulge in the bladder wall (bladder diverticulum), tiredness, problems with walking (gait disturbance), possible uncontrolled reflex reaction of the body (e.g. profuse sweating, throbbing headache or increase in pulse rate) around the time of the injection (autonomic dysreflexia) or falls1.
Many patients with neurogenic bladder do not actively talk to their doctors or other healthcare professionals about their urinary leakage, hence may remain undiagnosed and under treated12. Current treatments are focussed primarily on oral anticholinergics as first line treatment and, if the condition cannot be managed with the anticholinergics, the last step for many patients is surgery. However, over 70% of patients with urinary incontinence stop taking oral anticholinergic treatments after just one year because of side effects or lack of efficacy and many are reluctant to have surgery, demonstrating the need for alternative minimally invasive treatments13.
In addition to the Mutual Recognition Procedure in
Notes to Editors
About Detrusor (Bladder) Overactivity
The detrusor muscle is the most important muscle of the bladder and
contracts when urinating
to squeeze out urine.
Otherwise, it remains relaxed to allow the bladder
to fill. Other muscles involved in urination include the urethral
sphincter muscles which control the flow of urine. Detrusor
overactivity is characterised by involuntary bladder contractions which
can lead to urinary incontinence (wetting or leaking) as well as urgency
to urinate or an increased need to urinate. It is commonly divided into
two categories: idiopathic detrusor overactivity (IDO) where the cause
is unknown and neurogenic detrusor overactivity (NDO) resulting from
neurogenic bladder. Neurogenic bladder occurs when the nerves
controlling the detrusor muscle, predominantly in the spinal cord, are
damaged — for example by lesions in the spine (such as plaques caused by
MS) or an injury to the spinal cord (SCI). Given the nature of their
underlying conditions, the nerve damage for most patients with
neurogenic bladder cannot be repaired. Reducing the number of
involuntary detrusor muscle contractions with BOTOX® is one way to treat
bladder issues in patients with NDO. Botulinum toxin is currently
recommended in the 2011
Countries involved in the Mutual Recognition Procedure (MRP)
BOTOX® (botulinum toxin type A) from
- blepharospasm (uncontrolled blinking of the eyelids)
- hemifacial spasm (a neuromuscular disorder characterised by unpredictable and involuntary twitching of facial muscles on one side of the face)
- cervical dystonia (a muscle condition affecting the neck making it difficult to hold the head up straight)
- severe axillary hyperhidrosis (excessive sweating) of the armpits
- treatment of post stroke spasticity in the hand and wrist
- prophylaxis of headaches in adults who have chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine)
In addition, BOTOX® is also indicated to treat dynamic equinus foot deformity in children aged two years and older who have cerebral palsy.
Allergan's botulinum toxin type A is licensed under the brand name of VISTABEL® for the treatment of glabellar lines (frown lines).
This press release contains "forward-looking statements", including but
not limited to the statements by
1. Mutual Recognition Procedure BOTOX® Summary of Product Characteristics
2. Kalsi V et al. Therapy Insight: bladder dysfunction associated with multiple sclerosis. Nat Clin Pract Urol. 2005;2(10):492-501.
3. Giannontoni A et al. Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients. Neurourol Urodynamics. 1998;17:89-98
4. Erol B et al. The relationship between level of injury and bladder behavior in patients with post-traumatic spinal cord injury. Ulus Travma Acil Cerrahi Derg. 2009;15:377-382
5. Cruz F et al. Efficacy and Safety of OnabotulinumtoxinA in Patients with Urinary Incontinence Due to Neurogenic Detrusor Overactivity: A Randomised, Double-Blind, Placebo-Controlled Trial. Eur Urol (2011), doi:10.1016/ j.eururo.2011.07.002
6. Karsenty G et al. Botulinum toxin A (Botox) intradetrusor injections in adults with neurogenic detrusor overactivity/neurogenic overactive bladder: a systematic literature review. Eur Urol 2008; 53(2):275-87
9. Eurostat Population of EU http://epp.eurostat.ec.europa.eu/tgm/table.do?tab=table&language=en&pcode=tps00001&tableSelection=1&footnotes=yes&labeling=labels&plugin=1.
10. Tubaro A. Defining overactive bladder: epidemiology and burden of disease. Urology. 2004;64(6 Suppl 1):2-6.
11. Calabresi P et al. Impaired renal function in progressive multiple sclerosis. Neurology 2002;59;1799
12. Mahajan S et al. Under treatment of overactive bladder symptoms in patients with multiple sclerosis: An ancillary analysis of the NARCOMS patient registry. J Urol. 2010;183:1432-1437
13. Manack A et al. Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database. Neurourol Urodyn. 2010;30(3):395-401
15. BOTOX® Summary of Product Characteristics www.medicines.org.uk/emc/
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