People with disorders that cause muscle tightness and contractions can get relief from treatment with botulinum toxin. But a new study shows that about 15 percent of people treated with botulinum toxin type A for dystonia or spasticity can develop an immune response to the treatment itself, which can make the treatment less effective or stop working entirely. The study is published online in Neurology®, the medical journal of the American Academy of Neurology.
“People may be able to lessen their chances of developing this response by making sure the dose of the drug in each injection is as low as possible, the time between injections is not shortened and booster injections are avoided,” said study author Philipp Albrecht, MD, of Heinrich Heine University in Düsseldorf, Germany.
The study involved 596 people who had been receiving botulinum toxin type A for about three to five years for cervical dystonia, blepharospasm, facial hemispasm, or other types of dystonia and spasticity. The participants were still responding to the treatment. Overall, 14 percent of the people had developed the neutralizing antibodies that can lead to decreasing responsiveness to the drug.
A total 64 of the 408 people with cervical dystonia, or 16 percent, had developed the antibodies. Cervical dystonia affects the neck muscles. Of the 54 people with blepharospasm, which affects the eyelid muscles, three people, or 6 percent, had the antibodies.
Of the 52 people with other types of dystonia including Meige syndrome, which affects the jaw, tongue and eyes, nine people, or 17 percent, had the antibodies. Of the 33 people with spasticity, five people, or 15 percent, had the antibodies.
None of the 47 people with facial hemispasm, which affects the muscles on one side of the face, had the antibodies.
Using a special analysis to investigate the influence of the duration of treatment, the authors found that the development of antibodies increased over time. The analysis for the people with cervical dystonia, spasticity and other dystonias revealed that after about 15 years of treatment, the risk to develop antibodies is around 30 to 40 percent, while for people with blepharospasm the risk is around 15 percent.
The main factor associated with whether or not people developed the antibodies was the amount of a single dose of the drug, with those receiving doses above 700 unified dose units more likely to develop the antibodies.
The formulation of the drug that participants received was also associated with whether or not they developed antibodies. Most of the people, 324, received abobotulinumtoxin A; 68 received onabotulinumtoxin A and 46 received incobotulinumtoxin A. An additional 158 people received more than one formulation of the drug.
Six percent of those receiving only abobotulinumtoxin A developed the antibodies, and 7 percent of those receiving only onabotulinumtoxin A. None of the people receiving only incobotulinumtoxin A developed the antibodies. However, Albrecht noted that the treatment duration was shorter for people receiving incobotulinumtoxin A than for those receiving other formulations. He suggested that further studies are needed to include people treated with incobotulinumtoxin A for longer periods of time and people treated with onabotulinumtoxin for migraine or hyperhidrosis, which is increased sweating.
A limitation of the study is that some participants may have discontinued treatment with botulinum toxin because the treatment stopped working before they could be enrolled in the study, so it is possible that the rate of people with antibodies could have been higher.
Funding for some of the tests used in the study was provided by a grant from Merz Pharmaceuticals.
The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 34,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.
For more information about the American Academy of Neurology, visit AAN.com
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