The Emerging Role of Neurotoxins for the Treatment of Upper Limb Spasticity

One expert addresses the evolving standards of care and strategies for enabling patients to receive optimal care.

A Q&A with David M. Simpson, MD

While several therapeutic options are available for post-stroke patients with upper limb spasticity (ULS), effective management has proven difficult. However, the recent emergence of botulinum toxins as potential first-line agents provides reason for hope that more patients with spasticity can receive optimal treatment. According to David M. Simpson, MD, lead author of the Report of the Therapeutics and Technology Assessment Committee of the American Academy of Neurology (AAN) assessing botulinum neurotoxin for the treatment of spasticity, botulinum toxins offer a safe and effective means of managing ULS and could play a pivotal role in the shifting treatment paradigm for spasticity. Ahead, Dr. Simpson reflects on how this could change the spectrum of care going forward.

What are some of the challenges of spasticity management?

According to Dr. Simpson, the main difficulties of managing spasticity concern treatment more than diagnosis. “Many patients, particularly those who suffered acute stroke, are discharged to nursing homes and primary care physicians,” Dr. Simpson observes. Therefore, “management of spasticity is not handled very aggressively,” he continues. When they are no longer under the care of specialists, patients are underserved by not having the proper access to treatment.

Practical Pointers

Management of upper limb spasticity is challenging because patients are often discharged to nursing homes and primary care physicians and do not receive appropriate care. Over the last several years, botulinum toxins have emerged as a standard of care and first-line agents, offering patients an alternative to traditional oral therapy. It is important for neurologists and physiatrists to be trained in proper techniques and communicate with other healthcare providers, whether for botulinum toxin injection by the provider or in referral to the appropriate expert.

How has the standard of care for ULS evolved in recent years?

Several treatment options are available for spasticity, but ULS in particular has gained increased attention with the approvals of Botox (onabotulinumtoxinA, Allergan) and more recently Dysport (abobotulinumtoxinA, Ipsen Biopharmaceuticals) for that indication.

Dr. Simpson, a principal investigator on many studies of the treatment of spasticity with botulinum toxins, notes that the momentum for the use of toxins has increased significantly in recent years. “There have certainly been quite a few more studies published for use of toxins in spasticity, but one thing that we focused on in our recent review was in addition to reviewing toxins in general we looked at each of the forms of botulinum toxin individually,” says Dr. Simpson. “There are four different types of botulinum toxin commercially available in the US. We looked at evidence base for each, and one of the key points that comes out in reviewing literature is that the drugs are not interchangeable in terms of extrapolating efficacy and safety data from one to the other,” Dr. Simpson says. Thus, Dr. Simpson and his co-authors concluded that safety and efficacy may vary depending on the agent selected. “While there are commonalities across the entire class of botulinum toxins, they need to be looked at individually,” says Dr. Simpson. “It behooves all of us in the medical community to educate patients and families of patients, as well as colleagues in other specialties, that effective therapies are available for spasticity,” says Dr. Simpson.

How do botulinum toxins figure into the current treatment paradigm for spasticity and ULS in particular?

Not only are botulinum toxins a standard of care for the treatment of spasticity, according to Dr. Simpson, but there is also mounting evidence to suggest that they should be considered a first-line therapy for ULS. A head-to-head placebo-controlled study published by Dr. Simpson’s group showed that onabotulinumtoxin was more effective and safer than oral tizanadine in the treatment of upper limb spasticity.1 These findings reinforce that notion that botulinum toxins may indeed be first-line even before oral therapy, according to Dr. Simpson. He observes that botulinum toxins have also been proven safe and effective in the treatment of lower limb spasticity, an indication for which toxins are not yet FDA approved. “A recent placebo-controlled study presented at the 2015 Annual AAN meeting showed that botulinum toxin was superior to placebo in the treatment of lower limb spasticity.”2

However, Dr. Simpson notes that therapeutic selection in a clinical setting is not an “either/or” proposition and that the availability of multiple treatment modalities is beneficial for patients. “One of the things that has changed in medicine is that we are moving toward an era called ‘Rational Polypharmacy’,” he says. “The basic principle is that one uses any and all therapies and mixes and matches them together as long as it’s done in a rational and safe way. One can certainly consider that a patient may be treated with numerous therapies—physical and occupational therapy, botulinum toxin, oral agents, and even an intrathecal baclofen pump in the appropriate setting—that are each brought in at different times,” Dr. Simpson notes. “One can’t necessarily treat all of the muscles affected by spasticity with botulinum toxins.” Thus, there will still be a significant role for other treatment modalities in addition to botulinum toxin, according to Dr. Simpson.

In terms of how the treatment paradigm will evolve from here, Dr. Simpson notes that the development of guidelines concerning polypharmacy may present a challenge, given logistical difficulties of funding research into combination regimens. “There are few with the incentive to study and fund trials examining the combination of different agents and modalities,” he says.

Given the advances made regarding the use of botulinum toxins, what tips can you offer for the successful integration of these agents as standards of care continue to evolve?

“There are some very effective treatments with robust data for both upper and lower spasticity, including emerging data on toxins,” says Dr. Simpson. With indications for ULS and strong data for other off-label uses, Dr. Simpson points out that botulinum toxins are typically reimbursed by insurance companies, including off-label indications when supported by robust data.

However, before using these medications, it is important that physicians become educated on injection techniques and best practices, Dr. Simpson observes. “Some expertise and knowledge of anatomy is required to perform the injections properly, including optimal needle localization techniques, such as EMG, electrical stimulation, and ultrasound.” It is important for neurologists and physiatrists to be trained in proper techniques and communicate with other healthcare providers, whether for botulinum toxin injection by the provider or in referral to the appropriate expert, Dr. Simpson notes. “It is incumbent upon us to be knowledgeable about the data, to provide the expertise to make this treatment available to patients, and also to teach colleagues in our own field and other fields that aren’t currently incorporating these agents.” n

David M. Simpson, MD, is a Professor of Neurology and Director of the Clinical Neurophysiology Laboratories and Neuromuscular Division at the Icahn School of Medicine at Mount Sinai Hospital.

1. Simpson DM, Gracies JM, Yablon S, et al. Botulinum neurotoxin vs tizanidine in upper limb spasticity: A placebo-controlled study. J Neurol Neurosurg Psych. 2009;80(4) :380-385.

2. Wein et al. AAN 2015 Annual Meeting abstr.


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Launched in 2002, Practical Neurology is a publication uniquely dedicated to presenting current approaches to patient management, synthesis of emerging research and data, and analysis of industry news with a goal to facilitate practical application and improved clinical practice for all neurologists. Our straightforward articles give neurologists tools they can immediately put into practice.