Download The Burden of Refractory Epilepsy

ISSUE OVERVIEW
Approximately 50 million people worldwide are affected by epilepsy, including nearly three
million people in the U.S.1, 2. According to the Epilepsy Foundation of America, epilepsy is the
third most common neurological disorder, with approximately 200,000 new cases of epilepsy
diagnosed annually; equal in prevalence to cerebral palsy, multiple sclerosis and Parkinson’s
disease combined. Epilepsy is associated with increased mortality: 25,000 to 50,000 people
will die of seizures and related causes each year2.
Epilepsy is characterized by recurrent seizures. A seizure occurs when the electrical system of
the brain malfunctions, which may cloud awareness, block normal communication and produce
a variety of undirected, uncontrolled and unorganized movements3.
The Burden of Refractory Epilepsy
Antiepileptic drugs (AEDs) are the primary option for treating epilepsy. While many patients
with epilepsy experience seizure reduction or control with AEDs, studies have shown that as
many as one-third of people with epilepsy are unable to achieve seizure control with
medications alone4,5.
Additionally, some combinations of multiple drugs produce side effects, such as drowsiness,
lethargy, weight changes and confusion6. AEDs can also produce an increased risk of suicidal
behavior for some patients7.
Epilepsy is considered drug-resistant when seizures are not adequately controlled by
medications or when the side effects of the medication are intolerable and prevent patients
from continuing with treatment8. Several studies have shown that the likelihood of seizure
control greatly diminishes with each unsuccessful AED trial, such that after three AEDs, the
chances of seizure control with the next drug is nearly zero4. In 2009, the International League
1
Epilepsy Fact Sheet, World Health Organization.October 2012. Accessed online from
http://www.who.int/mediacentre/factsheets/fs999/en/
2
Epilepsy Foundation of America. Epilepsy Fact Sheet. Accessed on February 12, 2013 from
http://www.epilepsyfoundation.org/resources/newsroom/loader.cfm?csModule=security/getfile&PageID=21764
3
Epilepsy Foundation of America. Seizures Fact Sheet. Accessed on February 12, 2013 from
http://www.epilepsyfoundation.org/aboutepilepsy/seizures/index.cfm .
4
Kwan P., Brodie M.J. Early Identification of Refractory Epilepsy. New England Journal of Medicine.
2000;342:314-319.
5
Schiller Y., Najjar Y. Quantifying the response to antiepileptic drugs: Effect of past treatment history. Neurology
2008;70;54-65.
6
Mattson R.H. Monotherapy trials: endpoints. Epilepsy Research. 2001;45:109-117.
7
U.S. Food and Drug Administration. Suicidal Behavior and Ideation and Antiepileptic Drugs. Accessed on
February 12, 2013 from http://www.fda.gov/cder/drug/infopage/antiepileptics/default.htm.
8
Kwan P., et al. Definition of Drug Resistant Epilepsy: Consensus Proposal by the ad hoc Task Force of the ILAE
Commission on Therapeutic Strategies. Epilepsia. 2010; 51(6): 1069–1077.
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Against Epilepsy (ILAE) published a consensus statement defining drug-resistant epilepsy as
the failure of two AED trials to provide sustained freedom from seizures8.
People living with seizures that are not controlled, or with significant drug-induced side effects,
face many challenges. Daily tasks, such as going to work each day or caring for a child, can be
difficult or impossible for those with drug-resistant epilepsy. People with epilepsy are more
likely to experience overall poorer health, unemployment, and other medical conditions when
compared with the population that doesn’t have epilepsy9.
Uncontrolled seizures are associated with cognitive and memory impairment, high rates of
depression, higher risk of accidental injuries and increased health care resource utilization10.
These health care issues related to epilepsy – such as a broken arm during a fall or emergency
room visit due to a seizure, as well as lost productivity – are costly. According to the Centers for
Disease Control (CDC), epilepsy results in an estimated annual cost of $15.5 billion in medical
costs and lost or reduced earnings and production11.
VNS Therapy®
Fortunately, non-drug treatments are available and offer many patients with drug-resistant
epilepsy improved seizure control and quality of life. Cyberonics’ VNS Therapy, available in
Europe since 1994 and United States Food & Drug Administration (FDA)-approved in 1997, is
the only device-based treatment approved for epilepsy in the United States. VNS Therapy is
approved in the U.S. as an adjunctive, or add on, therapy in reducing the frequency of seizures
in adults and adolescents over 12 years of age with partial onset seizures which are resistant to
antiepileptic medications. In the European Union, VNS Therapy is approved for use as an
adjunctive therapy in reducing the frequency of seizures in patients whose epileptic disorder is
dominated by partial seizures (with or without secondary generalization) or generalized
seizures that are refractory, or resistant, to antiepileptic medications12.
VNS Therapy consists of a pacemaker-like device the size of a small watch and weighing less
than one ounce. The device, or generator, is usually implanted in the left chest area during an
outpatient procedure that does not involve brain surgery. A thin thread-like wire, or lead,
connected to the generator, runs under the skin and is attached to the left vagus nerve in the
neck. The device delivers mild, intermittently-pulsed signals to the vagus nerve, which then
activates various areas of the brain. Using an external dose adjustment system, physicians
9
Kobau, R. et al. Epilepsy Surveillance Among Adults --- 19 States, Behavioral Risk Factor Surveillance System.
CDC Morbidity and Mortality Weekly Report. 2008; 57 1-20.
10
Helmers S.L., et al. Clinical and economic impact of vagus nerve stimulation therapy in patients with
drug-resistant epilepsy. Journal of Epilepsy and Behavior, 2011; 22 (2): 370-5.
11
Epilepsy Fast Facts. Centers for Disease Control and Prevention. Accessed on May 5, 2013 from
http://www.cdc.gov/epilepsy/basics/fast_facts.htm
12
Cyberonics, Cyberonics Europe About VNS Therapy. Accessed on May 3, 2013 from
http://eu.cyberonics.com/en/vns-therapy-for-epilepsy/healthcare-professionals/vns-therapy
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adjust the stimulation duration, frequency and intensity. Treatment is automatically delivered
at regular intervals all day, every day so treatment is automatic and continuous.
Patients and their caregivers can use an external magnet that can be briefly held over the
implant site to produce an extra dose of stimulation. This extra dose can potentially shorten or
stop a seizure or decrease its intensity or the recovery period.
A meta-analysis of VNS Therapy efficacy, published in the August 12, 2011 issue of Journal of
Neurosurgery, evaluated 74 clinical studies with 3,321 patients suffering from drug-resistant
epilepsy, implanted with VNS Therapy. Results found that, on average, approximately 50 percent of
patients attained a clinically significant reduction in seizure frequency greater than 50 percent, with
about 12 percent experiencing a 90 percent decrease in seizures13.
Another study of 436 patients with drug-resistant epilepsy found that VNS Therapy, when used as
part of a multimodality treatment plan, resulted in an at least 50 percent reduction in seizures for
more than 60 percent of patients. In some cases, more than 40 percent of patients experienced at least
a 75 percent reduction in seizures14.
Additionally, studies have shown that the efficacy of VNS Therapy typically improves over time
15,16.
Earlier addition of non-drug treatments such as VNS Therapy may result in better outcomes for
patients with drug-resistant epilepsy. Research has shown that VNS Therapy can be effective
even when used after unsuccessful epilepsy brain surgery17.
The increased seizure control that most VNS Therapy patients experience can lead to improved
overall health and quality of life. In a 2011-published study conducted by Emory School of
Medicine researchers, an evaluation of 1,655 patients with drug-resistant epilepsy showed that
with the addition of VNS Therapy, patients experienced a lower occurrence of epilepsy-related
conditions, injuries and other health issues. Additionally, hospitalizations and emergency room
visits significantly decreased following treatment with VNS Therapy, and benefits were
sustained over time. As a result of reduced patient healthcare utilization and comorbidities, the
study showed VNS Therapy to be associated with significant, long-term healthcare cost savings
beginning 18 months after implantation10.
13
Englot, D J, et al. Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response.
Journal of Neurosurgery. Accessed on November 10, 2011 from http://thejns.org/doi/abs/10.3171/2011.7.JNS11977
14
Elliott, R.E. et al. Epilepsy & Behavior. Vagus nerve stimulation in 436 consecutive patients with treatmentresistant epilepsy: long-term outcomes and predictors of response.2011; 20(1):57-63.
15
Elliot, R.E., et. al. Efficacy of vagus nerve stimulation over time: Review of 65 consecutive patients with
treatment-resistant epilepsy treated with VNS >10 years. Epilepsy & Behavior. 2011, 3: 478-483
16
Schachter S.C. Vagus Nerve Stimulation Therapy Summary: Five Years After FDA Approval. Neurology. 2002;
59 (4):S15-S20.
17
Elliott, R.E. et al. Impact of Failed Intracranial Epilepsy Surgery on the Effectiveness of Subsequent
Vagus Nerve Stimulation. Neurosurgery. 2011; 69 (6):1210-1217.
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The side effects associated with VNS Therapy are typically mild to moderate, usually occur
during stimulation and often diminish over time. These side effects may include voice
alteration, tickling in the throat, cough and a feeling of shortness of breath18. Additionally,
because it is a non-drug treatment, VNS Therapy is sometimes considered an attractive
treatment option for women who are pregnant or wish to become pregnant19,20. Although the
safety and effectiveness of VNS Therapy have not been specifically studied in pregnant women,
healthy, full-term births have been reported with VNS Therapy. In addition, studies have not
shown any harm to the fetus21 22 23.
Most patients treated with VNS Therapy continue receiving the treatment long-term. Ninetyseven percent of patients continue with VNS Therapy after one year, and 72 percent after three
years18.
Focused on Device Solutions for Epilepsy
VNS Therapy has been used to treat more than 70,000 patients worldwide to date.

Cyberonics continues to focus on the development of VNS Therapy and other device
solutions for epilepsy. In February 2011, Cyberonics announced FDA approval of
AspireHC®, the fifth generation of VNS Therapy® technology. AspireHC incorporates
special features and functionality for the benefit of patients and their physicians, including
enhanced battery life, electronics and features that simplify programming. The AspireHC is
particularly beneficial for patients that require higher stimulation parameters.
Cyberonics remains committed to developing device-based solutions to help people with epilepsy
gain better control of their seizures and enjoy a higher quality of life and health.
For more information about VNS Therapy or Cyberonics, Inc., please visit www.cyberonics.com or
contact [email protected].
18
Morris G.L. III, Mueller W.M. Long Term Treatment with Vagus Nerve Stimulation of Patients with Refractory
Epilepsy. Neurology. 1999; 53:1731-1735.
19
Houser, M., Hennessy, M., Howard, B. Vagal Nerve Stimulator Use During Pregnancy for Treatment of
Refractory Seizure Disorder. Obstet Gynecol 2010;115:417–9.
20
Husain, M., Stegman, D., Trevino, K. Pregnancy and delivery while receiving vagus nerve stimulation for the
treatment of major depression: a case report. Annals of General Psychiatry 2005, 4:16.
21
Ben-Menachem, E. Neurostimulation—Past, Present, and Beyond. Epilepsy Curr 2012 Sep - Oct; 12(5): 188–
191.
22
Ben-Menachem, E. et al. Gestational Outcomes in Epilepsy Patients Receiving Vagus Nerve Stimulation.
Epileppsia 1998, 39:6.
23
Daniellson, I., et al. A pilot study of the teratogenicity of vagus nerve stimulation in a rabbit model. Brain
Stimulation 2009, 2: 41-9
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