Botox (onabotulinumtoxinA) is an injectable treatment approved to ease spasticity, a common symptom of multiple sclerosis (MS). In spasticity, muscles are abnormally stiff and tight, and prone to involuntary spasms.
The therapy also is approved for neurogenic detrusor overactivity (NDO) in MS, when nerve damage causes the muscle around the bladder to be overactive. This condition results in urinary incontinence and reduced quality of life.
Although Botox can ease these symptoms of MS, it does not alter the progression of the disease. The medication is marketed by Allergan, which is now part of AbbVie.
Botox contains a purified form of botulinum toxin type A, an extremely potent toxin that is produced by the bacteria Clostriudium botulinum. This toxin works by blocking the release of a chemical messenger called acetylcholine from nerve cells.
Under usual circumstances, acetylcholine from nerves binds to receptors on muscle cells, which prompts the muscles to contract. By blocking its release, Botox reduces the signal that makes muscles contract, which can help to ease conditions characterized by overactive muscles, like spasticity and neurogenic detrusor overactivity.
Botox is approved by the U.S. Food and Drug Administration (FDA) for the treatment of spasticity in individuals ages 2 and older.
The medication first received approval in 2010 for upper limb spasticity in adults. That was followed in 2016 by approval for lower limb spasticity in adults.
Botox’s use in children was authorized a few years later. It was approved for pediatric patients in June 2019 for upper limb spasticity, and in October 2019 for spasticity of the lower limbs.
The FDA also approved the therapy to treat NDO in adults and children ages 5 and up who either do not tolerate or do not respond to first-line treatment with anticholinergic medicines. The approval for adults was granted in 2011, and the indication was extended to children a decade later in 2021.
Botox is approved in the U.S. for several other health conditions, including chronic migraine, strabismus, and excessive sweating. The medication also is used in cosmetic applications and for cervical dystonia, a condition characterized by spasms in the neck muscles. According to Allergan, it is available in more than 90 countries worldwide.
Botox should not be used by anyone with a known allergy to the medication or any of its components. It also should not be given if there is an infection at the injection site.
Among those receiving treatment for urinary incontinence, the medication should not be injected into the bladder muscle (detrusor) if the individual has a urinary tract infection or urinary retention.
Botox is given via intramuscular injection directly to the affected parts of the body. Dosing is tailored based on the specific muscles that are being targeted for treatment.
To treat NDO in adults, the recommended dose is 200 units given across 30 injections into the detrusor muscle. The same dose, but given in smaller volumes across only 20 injections, is used for children with NDO who weigh at least 34 kg (about 75 lbs). For children under 34 kg, the recommended dose to treat NDO is 6 units/kg across 20 injections.
For spasticity in adults, the doses recommended are up to 400 units in the upper limbs, or 300–400 units in the lower limbs, divided across the affected muscles. Children with spasticity have a recommended dosage of 3–6 units/kg (maximum 200 units) in the upper limbs, or 4–8 units/kg (maximum 300 units) in the lower limbs, divided across the affected muscles.
Over a three-month period, an adult should not be given more than 400 units of Botox in total. For children, the maximum allowable dose in three months is either 10 units/kg or 340 units, whichever is lower.
Importantly, the strength of each Botox unit cannot be compared with other preparations of botulinum toxin products. The doses are not interchangeable with similar doses of other preparations.
Two clinical trials — the first (NCT00311376) launched in 2006, and the second (NCT00461292) started a year later in 2007 — served as the basis for the FDA’s approval of Botox for urinary incontinence due to detrusor overactivity associated with neurologic conditions. Notably, both studies were completed within a month of each other in 2010.
Sponsored by Allergan, the Phase 3 studies collectively enrolled 691 adults with NDO due to MS or spinal cord injury, who were experiencing at least 14 episodes of urinary incontinence per week.
Participants had failed to respond or were intolerant to anticholinergic medications. Each patient was randomly assigned to receive a total of 30 injections containing either a placebo or Botox, at a total dose of 200 or 300 units.
Results showed that 200 units of Botox significantly reduced weekly incontinence episodes after six weeks. The average decrease in the first trial was 21.8 with the medication and 13.2 with the placebo. Similar results were seen in the second study, with decreases of 21 versus 8.8 episodes. A similar change was seen after 12 weeks, and no additional benefits were observed with the 300 unit dose of Botox.
In both trials, patients were allowed to receive additional treatment with Botox at least 12 weeks from the first injections if they noticed a loss of effect. Based on the time to additional treatment, researchers estimated that the median duration of response to Botox was 42–48 weeks, which was much longer than the median of 13–18 weeks for patients on a placebo.
A Phase 3 study (NCT01852045) enrolled 114 children ages 5 to 17 who had NDO due to neurological conditions (mainly spinal cord deformities or injuries) and had not responded to standard anticholinergics. Participants were randomly assigned to different dosages of Botox — 50, 100, or 200 units, with a maximum allowable dose of 6 units per kg of body weight.
Results from the trial showed that all three doses led to a decrease in daily urinary incontinence episodes. Among patients given the 200 unit dose, the starting rate was 3.7 incontinence episodes per day, and this rate decreased by an average of 1.3 episodes per day after six weeks. While the three doses were similarly effective at lowering the episodes of urinary incontinence, the 200 unit dose was the best at increasing bladder capacity, data showed.
The FDA’s approvals of Botox to treat adults with spasticity were supported by findings from a total of seven clinical trials. These cumulatively enrolled more than 1,100 people with spasticity due to a stroke.
Six of the studies — including three Phase 3 trials: one that enrolled 170 patients (NCT01153815), another that involved 109 participants NCT00460564), and a third that included 124 individuals (NCT03261167) — evaluated the treatment of upper limb spasticity.
The seventh trial (NCT01575054), also Phase 3 and involving 468 patients, tested Botox for spasticity in the lower limbs.
Across all these studies, participants were given injections of either Botox or a placebo into affected muscles. Results broadly showed that, compared with the placebo, injections with Botox led to a significant reduction in muscle tone.
To evaluate Botox in children with spasticity, researchers conducted a global Phase 3 trial (NCT01603602). It included 234 children ages 2 to 16 who had spasticity in the upper limbs due to cerebral palsy or stroke. Participants were given injections of Botox (3 or 6 units/kg) or a placebo in the affected muscles.
Trial results showed that muscle tone scores, as measured with the Modified Ashworth scale (MAS), were significantly lower for patients given Botox, from week two to the final assessment at week 12. Clinician-reported measures of overall health tended to favor Botox over the placebo, but the difference was not statistically significant.
A separate pediatric Phase 3 trial (NCT01603628) tested Botox in children with lower limb spasticity due to cerebral palsy. This study enrolled 381 children ages 2 to 16 who were given the therapy (4 or 8 units/kg) or a placebo.
Results from the trial showed a significant reduction in muscle tone after two weeks, compared with the placebo. That reduction was sustained until week eight, with the effects wearing off at week 12. In addition, from weeks two to six, clinician-reported measures of overall health were significantly higher for those given 8 units/kg Botox compared with those given a placebo.
The most common side effects of Botox in NDO clinical trials have included:
When used in clinical trials to treat spasticity, the most common side effects of Botox included:
Botox is a toxin. Thus, its effects can spread beyond the injection site and cause symptoms consistent with the toxin’s effects, such as muscle weakness. These symptoms, which may develop hours to weeks after the initial injection, can result in breathing and swallowing difficulties that may be fatal.
The risk of these reactions may be increased in people with underlying neuromuscular conditions. Patients who experience problems with speech, breathing, or swallowing after being treated with Botox should seek immediate medical attention.
When used for the treatment of spasticity, Botox may increase the risk of upper respiratory tract infections and bronchitis, a condition marked by inflammation of the bronchial tubes that carry air to the lungs.
Patients given Botox for bladder-related conditions should be monitored for the retention of an abnormal amount of urine in their bladder after urination. In some cases, catheterization may be required to remove the retained urine.
Botox has not been adequately studied in pregnant people in clinical trials, but animal data suggest that the medication can negatively affect fetal growth.
It is not clear if Botox can increase the risk of side effects in nursing infants. The medication should only be used during breastfeeding if the potential benefits outweigh the risks.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Botox first received approval from the U.S. Food and Drug Administration in 1989 for use in two rare eye disorders. Approvals for adults and children with upper and lower limb spasticity then came in 2010, 2016, and 2019; spasticity is common in patients with multiple sclerosis, cerebral palsy, and stroke. The medication was cleared for neurogenic detrusor overactivity in adults in 2011 and expanded to children in 2021.
While Botox has not been rigorously studied in pregnant people, data from animal studies suggest that it can cause harm to a developing fetus. Patients on Botox who become pregnant or plan to do so are advised to discuss with their healthcare team the potential benefits and risks of continued treatment.
It is generally recommended that patients who are being treated with Botox avoid drinking alcohol for at least a day or two before and after they receive injections. Alcohol can thin the blood and increase the risk of bruising. Patients are advised to talk with their healthcare team about specific instructions regarding alcohol use and their treatment regimen.
Some participants in clinical trials have seen benefits from Botox treatment in as little as two to six weeks, depending on their specific condition. Trials investigating the therapy for neurogenic detrusor overactivity have reported a significant reduction in episodes of urinary incontinence as early as six weeks. For treatment of spasticity, trials have reported significant differences in muscle tone starting about two weeks after the first injections.
Neither hair loss nor weight gain was reported as a common side effect of Botox in clinical trials. There have been reports of patients who experience alopecia (hair loss) while on Botox, but it is not totally clear whether this effect is attributable to the medication. Patients who experience unexpected reactions after starting a new treatment are advised to discuss such effects with their healthcare team.
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