Injectable Anti-Aging/Anti-Wrinkle Treatments
(BOTOX)
What is BOTOX®?
BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex is a therapeutic
muscle-relaxing agent that helps reduce the uncontrollable muscular contractions and
associated pain that characterize cervical dystonia. It belongs to a class of drugs called
neurotoxins.
BOTOX® is the brand name of a unique product that is available only from Allergan. It is not
interchangeable with other products that contain botulinum neurotoxin. BOTOX® inhibits the
nerve impulses that trigger muscle hyperactivity. By relaxing hyperactive neck and shoulder
muscles, BOTOX® injection can improve head position and reduce pain in patients with
cervical dystonia.1
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What are the different botulinum neurotoxin
serotypes?
Botulinum toxin type A is 1 of 7 distinct botulinum neurotoxin serotypes referred to
alphabetically as A, B, C1, D, E, F, and G. Each serotype has different properties and actions.
No two botulinum products are alike.
The serotypes were first distinguished in the early 1900s when scientists noticed that animals
showed certain distinct biological responses to botulinum toxins obtained from different
sources.4 These researchers called the two different botulinum toxins types A and B.
Botulinum toxin type A was the first serotype developed for clinical use and is still the most
studied of the 7 serotypes. The unique properties of BOTOX® result from both the A
serotype, which is the most studied, and the unique Allergan manufacturing processes
updated in 1997. (For more information please see the question regarding the difference
between original and current BOTOX®)
How can I help maintain my response to
BOTOX® over the long term?
Minimizing the risk of antibody formation may help to maintain clinical response to
BOTOX® over the long term. The factors that contribute to neutralizing antibody formation
have not been well characterized. However, several of the factors that have been associated
with antibody formation are individual genetic characteristics and overall exposure to
neurotoxin complex protein.
Some individuals have a predisposition toward antibody formation because of certain genetic
characteristics. Although it is not currently possible to control these individual genetic
characteristics, doctors can control the overall amount of neurotoxin complex protein to
which you are exposed. There are at least 3 important features of neurotoxin complex protein
load exposure.
Protein Load Per Effective Dose. Exposure to higher amounts of foreign proteins is associated
with a higher risk of antibody formation.9 Although well-controlled clinical studies with
BOTOX® have not been conducted, the results of several retrospective studies suggest that
the association between higher protein exposure and increased risk of antibody formation
holds true for botulinum toxins.10,11 Dr. Jankovic and his colleagues performed a
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retrospective comparison of 20 cervical dystonia patients who developed antibodies and 22
who did not. They concluded that there is “a link among the mean dose per treatment session,
total cumulative dose, and the development of BTX [botulinum toxin] antibodies.”11 As total
dose is increased, so is exposure to neurotoxin complex protein. Although this study was not
designed in a way that directly links protein and antibody formation, it does support this idea.
Frequency of Exposure. Frequent injections of a foreign protein have been shown to increase
the body’s immune response.13 This suggests that frequent injections of botulinum
neurotoxins may also increase the risk of antibody formation. In one retrospective study,
investigators compared a group of 8 patients who had stopped responding to treatment to 32
patients who were still responding.12 The nonresponders had received more frequent
injections and a higher percentage of booster injections than the responders. Based on these
results, Dr. Greene and his colleagues concluded that, “In order to minimize the risk of
developing BTX resistance ¼ we recommend that physicians wait as long as possible ¼
between BTX injections, avoid booster injections, and use the smallest possible doses.” 12
Although this study was not designed in a way that directly links the frequency of injections
and antibody formation, it does support this idea.
Dosing Experience. As doctors gain experience with a given product, they may be able to
better select the lowest effective dose for their patients and treat at the longest possible
injection intervals. By delivering the lowest amount of neurotoxin complex protein to patients
it may be possible to reduce the risk of antibody formation.
What is the difference between original and
current BOTOX®?
Original BOTOX® was used clinically from 1989 to 1997. In November 1997, the US FDA
approved the current preparation of BOTOX®. Original BOTOX® contained approximately
25 nanograms of neurotoxin complex protein per 100 units. In contrast, current BOTOX®,
which is more active than the original BOTOX®, contains approximately 5 nanograms of
neurotoxin complex protein per 100 units.
Why is this important?
The amount of botulinum toxin type A protein per dose is important because high protein
loads have been linked to the formation of antibodies.10,11
In a study of 192 cervical dystonia patients with an average disease duration of 11 years and
who had received multiple treatments with original BOTOX®, 17% had neutralizing
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antibodies at study entry.1 Although the antigenic potential of current BOTOX® has not been
fully studied, it is predicted to have a lower antigenic potential than the original product due
to its significantly reduced protein load.
For example, current BOTOX® results in a protein load of approximately 12 nanograms of
protein per injection, based on a dose of 236 units (the average dose used in the BOTOX®
phase 3 study for cervical dystonia1). This protein load is comparable to that received by
blepharospasm patients injected with original BOTOX®. Since antibody formation in
blepharospasm patients treated with the original product was relatively uncommon, it may be
predicted that cervical dystonia patients treated with current BOTOX® may also show a low
rate of antibody formation. If this prediction is true, cervical dystonia patients may be less
likely to develop neutralizing antibodies.
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