Neurology -- Correspondence for Naumann et al., 70 (19) 1707-1714

Correspondence published:

Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based: Alexander Mauskop, Ninan Mathew (14 July 2008)

Reply from the authors: David M. Simpson, Markus Naumann, Charles Argoff, Casey Childers, Janis Miyasaki, Stephen Silberstein, and Yuen So (14 July 2008)

Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based 14 July 2008

Alexander Mauskop,
New York Headache Center
30 East 76 Street, New York, NY 10021,
Ninan Mathew
Send Correspondence to journal:
Re: Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based

drmauskop{at}nyheadache.com Alexander Mauskop, et al.

Reports of Therapeutics and Technology Assessment Subcommittee of the Academy are usually considered to be objective and definitive statements that are read and followed by large numbers of neurologists and are taken into consideration by many insurance companies.
This makes reading parts of the latest assessment of botulinum neurotoxin (BoNT) in the treatment of autonomic disorders and pain particularly surprising and disappointing. [1] The authors state that “Based on published Class I and Class II studies, BoNT injection is probably ineffective in the treatment of episodic migraine”. [1]
This statement is based on two studies which were well conducted, but used what we know to be suboptimal doses of BoNT. One study used up to 25 units of BoNT and the second one 7.5 to 50 units. Most headache specialists who utilize BoNT in their daily practice use an average of 100 units.
Despite this, the report goes on to state unequivocally that “BoNT should not be considered in patients with episodic migraine and chronic tension-type headache.” We hope that the authors will issue a correction that will state that the treatment paradigms used in these studies were probably suboptimal and that no conclusion about the appropriateness of the use of BoNT in episodic migraine can be made.
Reference
1. Naumann M, So Y, Argoff CE et al. Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008;70:1707-1714.
Disclosures: The authors have no disclosures

Reply from the authors 14 July 2008

David M. Simpson,
Department of Neurology, Mount Sinai Medical Center
One Gustave Levy Place; Box 1052, New York, NY 10029,
Markus Naumann, Charles Argoff, Casey Childers, Janis Miyasaki, Stephen Silberstein, and Yuen So
Send Correspondence to journal:
Re: Reply from the authors

david.simpson{at}mssm.edu David M. Simpson, et al.

The purpose of our TTA Subcommittee evidence-based review is to provide an explicit and transparent process by which the published literature is translated into conclusions and recommendations. [1] Details of this analytic process and the schema for study classification are provided in the Clinical Practice Guideline Development Process Manual [2] and on the AAN website at www.aan.com/go/guidelines/development.
The author panel is comprised of individuals with extensive clinical and research experience with BoNT or the guideline process. Furthermore, TTA papers undergo many levels of review by external and internal experts. The highest quality literature available for the respective indications is chosen for analysis. Of the two Class I and two Class II analyzed studies in migraine, none showed a difference between BoNT and placebo on the predefined primary outcome measures. This resulted in the conclusion that BoNT is probably ineffective and the recommendation that it should not be considered in the treatment of episodic migraine (Level B).
While Mauskop and Mathew acknowledge that these studies were “well conducted”, they state without supportive evidence that they “used what we know to be suboptimal doses of BoNT”. We are not aware of a high quality dose-finding study to define the optimal BoNT dose for headache. In contrast to their comment that the maximal dose in these studies was inadequate, one of the negative studies [3] incorporated a Botox® dose of 100 units, alleged by Mauskop to be that used by “most headache specialists”.
We are aware that there is wide variability among clinicians in BoNT injection technique in the treatment of headache. In addition to the dosing issues discussed above, some injectors use a flexible muscle selection “follow-the-pain” strategy, whereas the four reviewed studies all incorporated a fixed site selection paradigm. We thus indicated that “it is possible that underdosing and suboptimal muscle selection may account for some of the reported failures in studies of BoNT in headache.”
In order to acknowledge the limitations of such rigorous evidence-based reviews, the abstract states that “while clinicians’ practice may suggest stronger recommendations in some of these indications, evidence-based conclusions are limited by the availability of data”. It is possible that with greater experience gleaned from clinicians’ experience and prior negative studies, future trials may refine methodology and outcome measures to yield different results. If new, high-quality data is published that will alter the current conclusions and recommendations, the TTA will periodically update the guidelines to reflect this evidence.
References
2. Edlund W, Gronseth G, So Y, Franklin G. AAN Clinical Practice Guideline Process Manual. St. Paul: American Academy of Neurology. 2005.
3. Evers S, Vollmer-Haase J, Schwaag S, Rahmann A, Husstedt IW, Frese A. Botulinum toxin A in the prophylactic treatment of migraine--a randomized, double-blind, placebo-controlled study. Cephalalgia 2004;24:838-843.
Disclosures: Dr. Naumann has received speaker honoraria from Ipsen and Allergan and performs botulinum toxin injections. Dr. So holds financial interest in Satoris Inc., and has received research support from NIH, Pfizer, Inc., and NeurogesX, Inc. Dr. Argoff performs botulinum toxin injections. Dr. Childers has received speaker honoraria and research support from Allergan and performs botulinum toxin injections. Dr. Dykstra has received speaker honoraria from Allergan and Solstice, research support from Allergan, and performs botulinum toxin injections. Dr. Gronseth has received speaker honoraria from Pfizer, GlaxoSmithKline, Boehringer Ingelheim, and Ortho-McNeil. Dr. Jabbari has received research support from Allergan and performs botulinum toxin injections. Dr. Kaufmann has received speaker honoraria from Chelsea Therapeutics, research support from NIH, payment for expert testimony, and performs autonomic testing. Dr. Schurch has received speaker honoraria from Pfizer, Astellas, and Allergan; research support from Allergan, IFP, NCCR, and SNF; and performs autonomic testing and botulinum toxin injections. Dr. Silberstein has received speaker honoraria from GlaxoSmithKline, Allergan, AstraZeneca, Endo, Medtronic, Merck, J&J, Pfizer, Pozen, and Valeant Pharmaceuticals International; research support from Allergan, and performs botulinum toxin injections. Dr. Simpson has received speaker honoraria and research support from Allergan, Merz, and Solstice, Inc., and performs botulinum toxin injections.