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VANCOUVER – A new American Academy of Neurology practice guideline on the efficacy and safety evidence for botulinum toxin treatment of blepharospasm, cervical dystonia, spasticity, and headache has updated the last recommendations published in 2008, but leaves some relevant clinical concerns and off-label uses unaddressed.
The 2016 update, published April 18 in Neurology, adds new individual evidence for the use of the four branded formulations of the two commercially available botulinum toxin serotypes, A and B, for the aforementioned indications rather than lumping all recommendations for botulinum toxin together as in the 2008 guidelines. However, questions remain on the differences between the different products in clinical practice, especially since the formulations show little clinical difference in head-to-head comparisons for some of the indications, especially for the serotype A formulations.
In a press briefing on the new guidelines at the annual meeting of the American Academy of Neurology, guidelines coauthor Dr. Mark Hallett noted that nothing really surprised the experienced 14-member committee that put the guidelines together. “The reason that we chose these four different diseases is because we already had the sense that they were going to change in the particular ways that they did. We didn’t know exactly, of course, what was going to happen, but we had a sense that there were sufficient data that it was worth looking at them.”
For blepharospasm, the totality of evidence suggests that onabotulinumtoxinA (onaBoNT-A; Botox) and incobotulinumtoxinA (incoBoNT-A; Xeomin) injections should be considered and are probably safe and effective (level B recommendation), while abobotulinumtoxinA (aboBoNT-A; Dysport) may be considered (level C) and is possibly effective. The evidence shows that incoBoNT-A and onaBoNT-A have equivalent efficacy and aboBoNT-A and onaBoNT-A are possibly equivalent. There was not enough evidence to determine the efficacy of rimabotulinumtoxinB for blepharospasm (rimaBoNT-B; Myobloc).
The rigorousness of clinical trials in evaluating the efficacy and safety of botulinum toxin has evolved since the Food and Drug Administration approved onaBoNT-A and incoBoNT-A to treat blepharospasm, but no new trials have been conducted to give it a higher level of recommendation despite their well-known magnitude of benefit, said Dr. Hallett, chief of the National Institute of Neurological Disorders and Stroke medical neurology branch and its human motor control section.
New evidence added to the already well-established data on the effectiveness of botulinum toxin for cervical dystonia suggest that onaBoNT-A and incoBoNT-A are probably safe and effective and should be considered. In addition, aboBoNT-A and rimaBoNT-B have already proven effectiveness and safety and should be offered. The lack of class I studies for onaBoNT-A and incoBoNT-A led to the lower level of recommendation for them despite an extensive clinical history of their use in cervical dystonia, the guideline committee wrote (Neurology. 2016 Apr 18. doi: 10.1212/WNL.0000000000002560).
In adults with upper-limb spasticity, all three serotype A formulations – onaBoNT-A, aboBoNT-A, and incoBoNT-A – are effective and safe in reducing symptoms and improving passive limb function. All three achieved level A evidence to recommend that they should be offered. One comparative trial showed enough evidence to say that onaBoNT-A is probably superior to tizanidine for reducing upper-extremity tone and should be considered before it. RimaBoNT-B has level B evidence to advise that it should be considered and is probably safe and effective. None of the formulations have enough data to determine their efficacy on active limb function.
Fewer trials have examined the safety and effectiveness of botulinum toxin formulations for reducing lower leg spasticity in adults. The guidelines panel found enough evidence to recommend that aboBoNT-A and onaBoNT-A are safe and effective and should be offered (level A). There were no trials with high enough level of quality to determine whether incoBoNT-A or rimaBoNT-B were effective for lower-leg spasticity. None of the four agents had enough evidence to support their ability to improve active function associated with lower-limb spasticity.
At the press briefing, guidelines first author Dr. David M. Simpson expressed hope that a more refined methodology for evaluating spasticity might be achieved in future trials of botulinum toxin to detect the potentially subtle effects the agents may have on certain patients who are more likely to achieve benefits in active limb function. Currently, trials use a standardized set of outcomes to try to detect differences in patients with wide-ranging severity of symptoms and types of injury that led to spasticity. Dr. Simpson is professor of neurology at Mount Sinai in New York, as well as director of the neuromuscular diseases division and director of the clinical neurophysiology laboratories.
Positive results for onaBoNT-A in two pivotal trials in chronic migraine that were published since the last guidelines give the formulation the only FDA-approved indication for a botulinum toxin in chronic migraine and earned it a level A recommendation from the guidelines committee. However, in the trials it had a relatively small magnitude of efficacy in reducing the number of headache days by 15% versus placebo. The guidelines also advise not using onaBoNT-A in episodic migraine based on three negative trials. No high-quality trials have evaluated any formulation to change the overall 2008 guidelines’ advice that botulinum toxin is probably ineffective for treating chronic tension-type headaches.
Familiarity with appropriate dosing and side effects may allow clinicians to use the products off-label for indications in the guidelines for which clinical trials were not available, Dr. Richard L. Barbano of the movement disorders division at the University of Rochester noted in an editorial about the guidelines (Neurol Clin Pract. 2016 Apr 18. doi: 10.1212/CPJ.0000000000000244). “Off-label use is common in clinical practice. Little data exist to indicate that any of the different formulations, with attention to appropriate dosing and side effects, would not be effective in treating these other conditions. There are also a number of other neurologic conditions not discussed in the guideline in which botulinum toxin has shown efficacy, such as hemifacial spasm and other focal dystonias. Lack of sufficient high-level evidence to support a level A or B guideline recommendation does not negate their potential utility and likewise, there is little evidence to recommend one formulation over another.”
“In some circumstances where the drugs are relatively equivalent, some people prefer to stick with one so they get used to it more, and they can have more of a sense of what the dosing is, given that the doses may be different with the compounds and have different side effects,” Dr. Hallett said in an interview, noting that availability and price also might enter into a clinician’s decision on what to do.
Dr. Barbano also said that cost and value are becoming more important, and neurologists should consider when botulinum toxin therapy should be chosen among existing alternative treatment options, particularly for chronic migraine.
The guidelines are endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine and the American Society of Plastic Surgeons.
Dr. Hallett reported serving as chair of the Neurotoxin Institute Advisory Council and has received research grants from Allergan and Merz Pharmaceuticals. Dr. Simpson reported receiving research grants from and served as a consultant for Allergan, Ipsen, Merz Pharmaceuticals, and Acorda Therapeutics. Five other coauthors of the guidelines disclosed relationships with manufacturers of botulinum toxin formulations. Dr. Barbano reported serving on a scientific advisory board for Allergan and receiving research support from Allergan, Vaccinex, and Biotie.
VANCOUVER – A new American Academy of Neurology practice guideline on the efficacy and safety evidence for botulinum toxin treatment of blepharospasm, cervical dystonia, spasticity, and headache has updated the last recommendations published in 2008, but leaves some relevant clinical concerns and off-label uses unaddressed.
The 2016 update, published April 18 in Neurology, adds new individual evidence for the use of the four branded formulations of the two commercially available botulinum toxin serotypes, A and B, for the aforementioned indications rather than lumping all recommendations for botulinum toxin together as in the 2008 guidelines. However, questions remain on the differences between the different products in clinical practice, especially since the formulations show little clinical difference in head-to-head comparisons for some of the indications, especially for the serotype A formulations.
In a press briefing on the new guidelines at the annual meeting of the American Academy of Neurology, guidelines coauthor Dr. Mark Hallett noted that nothing really surprised the experienced 14-member committee that put the guidelines together. “The reason that we chose these four different diseases is because we already had the sense that they were going to change in the particular ways that they did. We didn’t know exactly, of course, what was going to happen, but we had a sense that there were sufficient data that it was worth looking at them.”
For blepharospasm, the totality of evidence suggests that onabotulinumtoxinA (onaBoNT-A; Botox) and incobotulinumtoxinA (incoBoNT-A; Xeomin) injections should be considered and are probably safe and effective (level B recommendation), while abobotulinumtoxinA (aboBoNT-A; Dysport) may be considered (level C) and is possibly effective. The evidence shows that incoBoNT-A and onaBoNT-A have equivalent efficacy and aboBoNT-A and onaBoNT-A are possibly equivalent. There was not enough evidence to determine the efficacy of rimabotulinumtoxinB for blepharospasm (rimaBoNT-B; Myobloc).
The rigorousness of clinical trials in evaluating the efficacy and safety of botulinum toxin has evolved since the Food and Drug Administration approved onaBoNT-A and incoBoNT-A to treat blepharospasm, but no new trials have been conducted to give it a higher level of recommendation despite their well-known magnitude of benefit, said Dr. Hallett, chief of the National Institute of Neurological Disorders and Stroke medical neurology branch and its human motor control section.
New evidence added to the already well-established data on the effectiveness of botulinum toxin for cervical dystonia suggest that onaBoNT-A and incoBoNT-A are probably safe and effective and should be considered. In addition, aboBoNT-A and rimaBoNT-B have already proven effectiveness and safety and should be offered. The lack of class I studies for onaBoNT-A and incoBoNT-A led to the lower level of recommendation for them despite an extensive clinical history of their use in cervical dystonia, the guideline committee wrote (Neurology. 2016 Apr 18. doi: 10.1212/WNL.0000000000002560).
In adults with upper-limb spasticity, all three serotype A formulations – onaBoNT-A, aboBoNT-A, and incoBoNT-A – are effective and safe in reducing symptoms and improving passive limb function. All three achieved level A evidence to recommend that they should be offered. One comparative trial showed enough evidence to say that onaBoNT-A is probably superior to tizanidine for reducing upper-extremity tone and should be considered before it. RimaBoNT-B has level B evidence to advise that it should be considered and is probably safe and effective. None of the formulations have enough data to determine their efficacy on active limb function.
Fewer trials have examined the safety and effectiveness of botulinum toxin formulations for reducing lower leg spasticity in adults. The guidelines panel found enough evidence to recommend that aboBoNT-A and onaBoNT-A are safe and effective and should be offered (level A). There were no trials with high enough level of quality to determine whether incoBoNT-A or rimaBoNT-B were effective for lower-leg spasticity. None of the four agents had enough evidence to support their ability to improve active function associated with lower-limb spasticity.
At the press briefing, guidelines first author Dr. David M. Simpson expressed hope that a more refined methodology for evaluating spasticity might be achieved in future trials of botulinum toxin to detect the potentially subtle effects the agents may have on certain patients who are more likely to achieve benefits in active limb function. Currently, trials use a standardized set of outcomes to try to detect differences in patients with wide-ranging severity of symptoms and types of injury that led to spasticity. Dr. Simpson is professor of neurology at Mount Sinai in New York, as well as director of the neuromuscular diseases division and director of the clinical neurophysiology laboratories.
Positive results for onaBoNT-A in two pivotal trials in chronic migraine that were published since the last guidelines give the formulation the only FDA-approved indication for a botulinum toxin in chronic migraine and earned it a level A recommendation from the guidelines committee. However, in the trials it had a relatively small magnitude of efficacy in reducing the number of headache days by 15% versus placebo. The guidelines also advise not using onaBoNT-A in episodic migraine based on three negative trials. No high-quality trials have evaluated any formulation to change the overall 2008 guidelines’ advice that botulinum toxin is probably ineffective for treating chronic tension-type headaches.
Familiarity with appropriate dosing and side effects may allow clinicians to use the products off-label for indications in the guidelines for which clinical trials were not available, Dr. Richard L. Barbano of the movement disorders division at the University of Rochester noted in an editorial about the guidelines (Neurol Clin Pract. 2016 Apr 18. doi: 10.1212/CPJ.0000000000000244). “Off-label use is common in clinical practice. Little data exist to indicate that any of the different formulations, with attention to appropriate dosing and side effects, would not be effective in treating these other conditions. There are also a number of other neurologic conditions not discussed in the guideline in which botulinum toxin has shown efficacy, such as hemifacial spasm and other focal dystonias. Lack of sufficient high-level evidence to support a level A or B guideline recommendation does not negate their potential utility and likewise, there is little evidence to recommend one formulation over another.”
“In some circumstances where the drugs are relatively equivalent, some people prefer to stick with one so they get used to it more, and they can have more of a sense of what the dosing is, given that the doses may be different with the compounds and have different side effects,” Dr. Hallett said in an interview, noting that availability and price also might enter into a clinician’s decision on what to do.
Dr. Barbano also said that cost and value are becoming more important, and neurologists should consider when botulinum toxin therapy should be chosen among existing alternative treatment options, particularly for chronic migraine.
The guidelines are endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine and the American Society of Plastic Surgeons.
Dr. Hallett reported serving as chair of the Neurotoxin Institute Advisory Council and has received research grants from Allergan and Merz Pharmaceuticals. Dr. Simpson reported receiving research grants from and served as a consultant for Allergan, Ipsen, Merz Pharmaceuticals, and Acorda Therapeutics. Five other coauthors of the guidelines disclosed relationships with manufacturers of botulinum toxin formulations. Dr. Barbano reported serving on a scientific advisory board for Allergan and receiving research support from Allergan, Vaccinex, and Biotie.
VANCOUVER – A new American Academy of Neurology practice guideline on the efficacy and safety evidence for botulinum toxin treatment of blepharospasm, cervical dystonia, spasticity, and headache has updated the last recommendations published in 2008, but leaves some relevant clinical concerns and off-label uses unaddressed.
The 2016 update, published April 18 in Neurology, adds new individual evidence for the use of the four branded formulations of the two commercially available botulinum toxin serotypes, A and B, for the aforementioned indications rather than lumping all recommendations for botulinum toxin together as in the 2008 guidelines. However, questions remain on the differences between the different products in clinical practice, especially since the formulations show little clinical difference in head-to-head comparisons for some of the indications, especially for the serotype A formulations.
In a press briefing on the new guidelines at the annual meeting of the American Academy of Neurology, guidelines coauthor Dr. Mark Hallett noted that nothing really surprised the experienced 14-member committee that put the guidelines together. “The reason that we chose these four different diseases is because we already had the sense that they were going to change in the particular ways that they did. We didn’t know exactly, of course, what was going to happen, but we had a sense that there were sufficient data that it was worth looking at them.”
For blepharospasm, the totality of evidence suggests that onabotulinumtoxinA (onaBoNT-A; Botox) and incobotulinumtoxinA (incoBoNT-A; Xeomin) injections should be considered and are probably safe and effective (level B recommendation), while abobotulinumtoxinA (aboBoNT-A; Dysport) may be considered (level C) and is possibly effective. The evidence shows that incoBoNT-A and onaBoNT-A have equivalent efficacy and aboBoNT-A and onaBoNT-A are possibly equivalent. There was not enough evidence to determine the efficacy of rimabotulinumtoxinB for blepharospasm (rimaBoNT-B; Myobloc).
The rigorousness of clinical trials in evaluating the efficacy and safety of botulinum toxin has evolved since the Food and Drug Administration approved onaBoNT-A and incoBoNT-A to treat blepharospasm, but no new trials have been conducted to give it a higher level of recommendation despite their well-known magnitude of benefit, said Dr. Hallett, chief of the National Institute of Neurological Disorders and Stroke medical neurology branch and its human motor control section.
New evidence added to the already well-established data on the effectiveness of botulinum toxin for cervical dystonia suggest that onaBoNT-A and incoBoNT-A are probably safe and effective and should be considered. In addition, aboBoNT-A and rimaBoNT-B have already proven effectiveness and safety and should be offered. The lack of class I studies for onaBoNT-A and incoBoNT-A led to the lower level of recommendation for them despite an extensive clinical history of their use in cervical dystonia, the guideline committee wrote (Neurology. 2016 Apr 18. doi: 10.1212/WNL.0000000000002560).
In adults with upper-limb spasticity, all three serotype A formulations – onaBoNT-A, aboBoNT-A, and incoBoNT-A – are effective and safe in reducing symptoms and improving passive limb function. All three achieved level A evidence to recommend that they should be offered. One comparative trial showed enough evidence to say that onaBoNT-A is probably superior to tizanidine for reducing upper-extremity tone and should be considered before it. RimaBoNT-B has level B evidence to advise that it should be considered and is probably safe and effective. None of the formulations have enough data to determine their efficacy on active limb function.
Fewer trials have examined the safety and effectiveness of botulinum toxin formulations for reducing lower leg spasticity in adults. The guidelines panel found enough evidence to recommend that aboBoNT-A and onaBoNT-A are safe and effective and should be offered (level A). There were no trials with high enough level of quality to determine whether incoBoNT-A or rimaBoNT-B were effective for lower-leg spasticity. None of the four agents had enough evidence to support their ability to improve active function associated with lower-limb spasticity.
At the press briefing, guidelines first author Dr. David M. Simpson expressed hope that a more refined methodology for evaluating spasticity might be achieved in future trials of botulinum toxin to detect the potentially subtle effects the agents may have on certain patients who are more likely to achieve benefits in active limb function. Currently, trials use a standardized set of outcomes to try to detect differences in patients with wide-ranging severity of symptoms and types of injury that led to spasticity. Dr. Simpson is professor of neurology at Mount Sinai in New York, as well as director of the neuromuscular diseases division and director of the clinical neurophysiology laboratories.
Positive results for onaBoNT-A in two pivotal trials in chronic migraine that were published since the last guidelines give the formulation the only FDA-approved indication for a botulinum toxin in chronic migraine and earned it a level A recommendation from the guidelines committee. However, in the trials it had a relatively small magnitude of efficacy in reducing the number of headache days by 15% versus placebo. The guidelines also advise not using onaBoNT-A in episodic migraine based on three negative trials. No high-quality trials have evaluated any formulation to change the overall 2008 guidelines’ advice that botulinum toxin is probably ineffective for treating chronic tension-type headaches.
Familiarity with appropriate dosing and side effects may allow clinicians to use the products off-label for indications in the guidelines for which clinical trials were not available, Dr. Richard L. Barbano of the movement disorders division at the University of Rochester noted in an editorial about the guidelines (Neurol Clin Pract. 2016 Apr 18. doi: 10.1212/CPJ.0000000000000244). “Off-label use is common in clinical practice. Little data exist to indicate that any of the different formulations, with attention to appropriate dosing and side effects, would not be effective in treating these other conditions. There are also a number of other neurologic conditions not discussed in the guideline in which botulinum toxin has shown efficacy, such as hemifacial spasm and other focal dystonias. Lack of sufficient high-level evidence to support a level A or B guideline recommendation does not negate their potential utility and likewise, there is little evidence to recommend one formulation over another.”
“In some circumstances where the drugs are relatively equivalent, some people prefer to stick with one so they get used to it more, and they can have more of a sense of what the dosing is, given that the doses may be different with the compounds and have different side effects,” Dr. Hallett said in an interview, noting that availability and price also might enter into a clinician’s decision on what to do.
Dr. Barbano also said that cost and value are becoming more important, and neurologists should consider when botulinum toxin therapy should be chosen among existing alternative treatment options, particularly for chronic migraine.
The guidelines are endorsed by the American Association of Neuromuscular & Electrodiagnostic Medicine and the American Society of Plastic Surgeons.
Dr. Hallett reported serving as chair of the Neurotoxin Institute Advisory Council and has received research grants from Allergan and Merz Pharmaceuticals. Dr. Simpson reported receiving research grants from and served as a consultant for Allergan, Ipsen, Merz Pharmaceuticals, and Acorda Therapeutics. Five other coauthors of the guidelines disclosed relationships with manufacturers of botulinum toxin formulations. Dr. Barbano reported serving on a scientific advisory board for Allergan and receiving research support from Allergan, Vaccinex, and Biotie.
AT THE AAN 2016 ANNUAL MEETING
