People with movement disorders such as dystonia and spasticity who receive injections of botulinum toxin type A, commonly known as Botox, over a long period of time may develop an immune response that makes treatment less effective or ineffective, especially when administered at higher doses, according to a study published in Neurology on January 1.
Botulinum toxin type A is a protein complex that can cause the immune system of some patients to respond by forming neutralizing antibodies that weaken the toxin’s effectiveness.
Previous studies on this phenomenon focused on one neurologic condition, or on patients who initially had a positive response to Botox therapy, but for whom the treatment was less effective with subsequent treatments.
To determine the prevalence of neutralizing antibodies in patients who received botulinum toxin injections for several neurologic conditions, the researchers recruited 596 people who had four injections over the course of one year from 2013 to 2014.
Patients were placed in different subgroups based on their disorder: 408 with cervical dystonia; 47 with facial hemispasm, an involuntary muscle contraction on one side of the face; 54 with blepharospasm, an involuntary blinking or spasm of eyelids; 52 with other types of dystonia; and 33 with spasticity.
To find out whether dosing influenced the development of neutralizing antibodies, the researchers subdivided patients into three different dose groups: 0 to 350 unified dose units (uDU); 351 to 700 uDU, and less than 700 uDU.
The researchers also drew blood from the patients—which was frozen for up to a year—to look for neutralizing antibodies.
Out of the 596 patients, 83 tested positive for neutralizing antibodies. Of that number, 64 had cervical dystonia, three had blepharospasm, nine had other types of dystonia, and five had spasticity. Patients with facial hemispasm did not produce these antibodies.
After about 15 years of treatment, the risk of producing neutralizing antibodies was 30 to 40 percent for patients with cervical dystonia, spasticity, and other dystonias. For patients with blepharospasm, the risk was 15 percent.
In addition, patients who received more than 350 uDU had a significantly higher risk than patients who received less than 350 uDU. Those treated with more than 700 uDU were at the highest risk, despite consistent reinjection intervals of between 12 and 13 weeks.
Drug formulation also influenced the risk of developing neutralizing antibodies. Among patients who received abobotulinumtoxinA, 6 percent developed antibodies compared to 7 percent who received onabotulinumtoxinA. Patients who were injected with incobotulinumtoxinA did not develop antibodies. A total of 158 people received more than one formulation of the drug.
Because people were treated with the toxin for different lengths of time, the researchers wrote, the finding needs to be corroborated in larger studies with consistent follow-up times.
Repeated and long-term injections of botulinum toxin increase the risk of developing neutralizing antibodies and the higher the dose the greater the risk. Therefore, they believe the dose per injection session should be kept as low as possible to minimize the risk of becoming resistant.
