VANCOUVER—The American Academy of Neurology (AAN) has updated its 2008 guidelines on the use of botulinum toxin for spasticity, cervical dystonia, blepharospasm, and migraine to reflect recent research. Unlike the 2008 guidelines, the current document describes the evidence for the four formulations of botulinum toxin individually. The guidelines were published online ahead of print April 18 in Neurology and presented at the 68th Annual Meeting of the AAN.
Botulinum toxin blocks the release of substances at nerve endings, generally resulting in reduced muscle contraction and decreased transmission of pain signals. The four preparations available in the United States are abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, and rimabotulinumtoxinB.
To develop the guideline, David M. Simpson, MD, Professor of Neurology and Neuromuscular Diseases at the Icahn School of Medicine at Mount Sinai Hospital in New York, and colleagues reviewed all available scientific studies on these formulations in the four conditions specified. The authors concluded that botulinum toxin is generally safe and effective for treating spasticity in adults, cervical dystonia, blepharospasm, and chronic migraine.
The new guideline’s recommendation on chronic migraine is a major change from the earlier document, said Dr. Simpson. In 2008, not enough evidence was available to support any recommendation on the use of botulinum toxin for chronic migraine. Since that time, two pivotal Class I studies demonstrated the effectiveness of onabotulinumtoxinA in the treatment of chronic migraine. The magnitude of the drug’s efficacy was small, however. In the four weeks after the first treatments, onabotulinumtoxinA was associated with an approximately 15% reduction in headache days per month, compared with placebo. The difference was statistically significant, and the new guideline contains a Level A recommendation of onabotulinumtoxinA for chronic migraine.
On the other hand, the authors found Level A evidence indicating a lack of effectiveness of onabotulinumtoxinA in episodic migraine. “It’s an interesting question as to whether there’s a pathophysiologic difference between episodic migraine and chronic migraine,” but the evidence is unclear, said Dr. Simpson. Another possible explanation for botulinum toxin’s lack of efficacy in this indication is that studies of episodic migraine may reflect a floor effect, he added. “If you have so few headaches per month … how much does that need to reduce to see a significant difference from placebo? That is perhaps one obvious concern about getting a positive result of those studies.” In addition, the authors concluded that abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA are effective in reducing excess muscle tone and should be offered to patients with upper limb spasticity. RimabotulinumtoxinB is probably effective for this indication and should be considered, according to the guideline. For lower limb spasticity, abobotulinumtoxinA and onabotulinumtoxinA are effective and should be offered.
The guideline also indicates that abobotulinumtoxinA and rimabotulinumtoxinB are effective for cervical dystonia and should be offered. OnabotulinumtoxinA and incobotulinumtoxinA are probably effective and should be considered for this indication.Researchers have conducted few well-designed studies on blepharospasm. OnabotulinumtoxinA and incobotulinumtoxinA are probably effective and should be considered for this indication, according to the guideline. AbobotulinumtoxinA is possibly effective and may be considered. The 2008 guidelines also discussed disorders such as essential tremor, hemifacial spasm, and disorders of the voice. No new evidence about botulinum toxin’s effect in these disorders was available at the time that the update was initiated, and they were not included.