As A Physician….

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As a physician who spends a lot of time treating patients with many forms of dystonia and spasticity with injections of botulinum toxin, I am often ask questions about Botulinum toxin type A (BOTOX®) and botulinum toxin type B ( MyoBlocT). I would like to share the commonly asked questions with you. Please keep in mind that each patient should discuss their individual case with their physician before making any changes in their treatment plan.

Question: Is MyoBlocT “stronger” than BOTOX?

Many patients are confused by the difference in units between the two toxins. The average dose for BOTOX is 100-250 units and the average starting dose for MyoBloc is 2500 to 10,000 units. The unit is based on the dose that it takes to kill 50% of a Swiss-Webster mouse. Please keep in mind that units are only based upon the affect in a mouse. In addition, different animals are affected differently by botulinum toxin type B. Difference in species reaction to different botulinum neurotoxins prevents generalization from animal studies to human doses. In the human, the doses needed to get more effect are higher for BTX-B than BTX-A. Theses doses were arrived at through several clinical trials monitored by the FDA. In the 1999 trial reported in the journal, Neurology, the dose of 10,000 Units of BTX-B was more effective than 5000 units in those patients who also had an effect from previous doses of less than 250 units of BTX-A. ADDIN ENRfu [1, 2]The bottom line is that the BTX-B is not stronger and current dosing differences are based on species variability and clinical trials.

Question: Is BOTOX or MyoBloc “better”?

There have been no head to head comparison studies of the two, although the Dystonia Study Group (DSG) head by Dr. Cynthia Comella has a large multi-center clinical trial underway. The results of that trial should be available in about 2 years. At this time we know that both of these drugs are effective in the treatment of cervical dystonia when judged against placebo (just saline or water only).

Question: Should I change from BTX-A to BTX-B?

If a patient is doing well with a particular regimen, I don’t recommend a change.

Those patients who should definitely try BTX-B are those who have documented resistance to BTX-A. Resistance means that you have been treated with 2 consecutive injections of BTX-A separated by at least 12 weeks and had no affect and no side effects. The presence of side effects without a benefit in the cervical dystonia suggests that the wrong dose and/or wrong muscles were used in treating the cervical dystonia. To determine resistance, some other test of immunity, such as a FTAT or UBI test is needed.

In these confirmatory tests, the physician injects a small amount of BTX-A generally 15 to 25 units in either the forehead (frontalis for FTAT) or in the muscle just above the nose that wrinkles with frowning (corrugators). There are other sites to inject as well, such the hand or foot muscles. If there is not an affect after 2 weeks, the patient is said to be resistant to BTX-A.

Dr. Mitchell Brin, et al, demonstrated in a 1999 Neurology journal article that patient’s who are resistant to BTX-A will respond to treatment with BTX-B.

For those patients who still have some affect from BTX-A, but that affect is less robust or not as long as when treatment was started with BTX-A, the answers are less clear. I always ask those patients whether they are back to as bad as they were before they started treatment. Depending on the answer, I may offer them treatment with BTX-B. I usually try to determine whether they are resistant before switching, so that I know their status if they don’t like the new treatment.

Question: What are the side effects of BTX-B?

In the clinical trials patients complained of dry mouth significantly more often than those who were treated with placebo only. In most patients the dry mouth was mild to moderate, limited and did not need treatment. In my practice, there are some patients who find the dry mouth to be very bothersome and rarely patients discontinue treatments because of this problem. In addition, some of those patients treated in the research studies also complained of mild to moderate swallowing problems after they received the injections. This was usually not a major problem and doesn’t result in stopping treatment. This problem can usually be taken care of by lowering the dose in the front of the neck (sternocleidomastoid muscle).

Question: What is the chance of becoming resistant to BTX-B?

The package insert for BTX-B suggests that for those patients who remain on BTX-B for one year and 18 months there was a positive mouse neutralization antibody test in 10% and 18% of the patients respectively. ADDIN ENRfu [3] The number of patients was small and this lumped all those who still responded to BTX-A and those who were resistant to BTX-A. Alternatively, the BTX-A package insert reports a 17% positive mouse neutralization antibody study in patients in whom their doctors still thought they were getting a result from the BTX-A injections before starting the study. ADDIN ENRfu [4] The 17% number was in those patient’s who were treated with the earlier formulation of BTX-A. Preliminary data on those patients who have received only the new formulation of BTX-A suggests that this number is substantially lower.

Unfortunately, at this time there is no information on the rate of antibody formation in patient’s with cervical dystonia over several years with either toxin available in the US. The FDA has mandated such studies and these have been underway over the last year. Many dystonia patients are donating blood at the time of injection with toxin to answer this question.

My current recommendation is to use good clinical judgment about the effectiveness of the current treatment plan. I don’t recommend alternating between the two toxins if at all possible. It is hoped that the results of the on-going studies will answer many of the questions about immunity.

Question: BTX-A is used for other things like spasticity after stroke and wrinkles. What do we know about BTX-B in such areas?

BTX-A has been on the market in the US since 1989, thus, allowing physicians plenty of time to find other creative and beneficial uses for this drug. BTX-B has been on the market since December of 2000, a much shorter time to allow such exploration. Preliminary studies of BTX-B in post-stroke spasticity suggest that it may be helpful, but the right starting dose is not known and complaints of dry mouth were common in our small study. Certainly, larger studies are needed to know whether this treatment will help these patients over the long-term. Physicians have explored using BTX-B for wrinkles. However, the use of BTX-B for wrinkles is currently not FDA approved and studies have not been performed to evaluate this in large patient populations.

Summary

The introduction of BTX-B in the US market offers patients and their physicians an alternative therapy for cervical dystonia. Both should review the available data on benefits and side effects and make individual decisions when changing or starting a therapy.

Allison Brashear, MD

Associate Professor of Neurology

Wake Forest School of Medicine/Neurology
Meads Hall 3rd Floor
Winston-Salem, NC 27157

Financial Disclosures: Dr. Brashear has been an investigator in clinical trials for Elan (maker of MyoBloc) and Allergan (maker of BOTOX). She has received honorariums from both companies for speeches.

ADDIN ENBbu 1. Brashear, A., et al., Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A- responsive cervical dystonia. Neurology, 1999. 53 (7): p. 1439-46.

2. Brin, M.F., et al., Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A- resistant cervical dystonia. Neurology, 1999. 53 (7): p. 1431-8.

3. Elan Pharmaceuticals, I., Myobloc package insert. December, 2000.

4. Allergan, I., BOTOX Package insert . December, 2000.

My mom and I wanted to thank you for hosting such a great symposium this year. This was our third year and we are looking forward to next years. E. Mathews