Can you feel it? Neurology treatments moving forward
Focus on Neurology
Conditions such as multiple sclerosis (MS), epilepsy, Parkinson disease (PD), and dementia are receiving more attention now than ever because of their prevalence, the debilitating nature of disease courses, and negative outcomes associated with suboptimal medication therapy. Pharmacists can guide patients with MS and epilepsy in choosing from among several new therapeutic options. Pharmacists also can help patients with PD to manage medications for nonmotor symptoms, and an issue to watch is the association between statin use and cognitive function in older patients.
New treatments for MS
“What is significant is that we now have several medications to treat MS that are effective, particularly if used early in the course of the disease,” said Melody Ryan, PharmD, MPH, who is Associate Professor of Pharmacy Practice and Science at the University of Kentucky (UK) College of Pharmacy and Associate Professor of Neurology at the UK College of Medicine. “Twenty years ago, there just wasn’t anything.”
MS is the most common disabling neurologic condition of young adults who typically are diagnosed between 20 and 40 years of age, according to the National Institute of Neurological Disorders and Stroke. Approximately 250,000 to 300,000 Americans are diagnosed with MS, which affects twice as many women as men. Treatments for MS are quite expensive, burdening the health care system.
The unpredictable nature of the disease course causes difficulty in diagnosing and treating it. Some patients may have a mild course with little disability, while others may have a steadily progressing disease with worsening symptoms and increased disability. “There is a big emphasis on earlier diagnosis and, thus, earlier treatment,” Ryan said. “Starting therapy as soon as you can and having a good, accurate diagnosis are really important.” Unfortunately, therapies do not improve neurologic damage that has already occurred. Current treatments focus on preventing relapse and lengthening remission.
In addition to the handful of disease-modifying drugs (DMTs) already in use, two new oral medications, dimethyl fumarate (Tecfidera—Biogen Idec) and teriflunomide (Aubagio—Sanofi) have been approved most recently by FDA. These two medications, along with fingolimod (Gilenya—Novartis) and dalfampridine (Ampyra—Acorda), provide MS patients with newer oral therapy instead of cumbersome injections.
Other drugs in the pipeline for 2014 include laquinimod (oral), peginterferon beta-1a, and two monoclonal antibodies, daclizumab and ocrelizumab (humanized version of rituximab). Peginterferon beta-1a is a modified formulation of interferon beta-1a with a longer half-life. FDA is currently reviewing this agent; a decision is expected in the spring of this year. Natalizumab is also pursuing an indication for secondary progressive MS.
FDA did not approve alemtuzumab for MS in a recent review because of concerns regarding safety compared with efficacy. The manufacturer, Genzyme, is appealing the review.
With increasing options to treat MS, “pharmacists can play a critical role in guiding and helping patients” choose which agent to use, said Jacci Bainbridge, PharmD, Professor of Clinical Pharmacy at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences.
“The literature suggests that 48% of the patients are nonadherent with the first DMT which takes time to work,” Bainbridge said. “You can’t treat just MS.” Patients may also need therapy for brain atrophy, urinary complications, or depression. “By increasing the adherence to MS, you can decrease other symptoms of MS,” she added. Pharmacists can help patients and prescribers choose an appropriate oral therapy based on the symptom presentation and also can monitor therapy for ADRs and drug–drug interactions.
Optimal therapy, education for epilepsy
The most common neurologic problem in the United States is epilepsy. About 2.3 million Americans have epilepsy, which costs the country approximately $12.5 billion each year, according to the National Institute of Neurological Disorders and Stroke. An estimated 25,000 to 50,000 die of seizures and related causes each year. “It can be life-threatening without a treatment or suboptimal therapy,” said Bainbridge.
About 20 FDA-approved antiepileptic medications (AEDs) are now on the market. New therapies include eslicarbazepine (Aptiom—Sunovion) and, from 2012, perampanel (Fycompa—Eisai). New formulations of existing drugs include topiramate extended release (Trokendi XR—Supernus) and oxcarbazepine (Oxtellar XR—Supernus). Treatments may differ based on the cause and symptom presentation, which vary widely from patient to patient.
For patients, managing epilepsy with medications may seem like a double-edged sword because AEDs have many adverse drug reactions (ADRs), which can be as debilitating as the disease itself, and drug interactions.
With AEDs, “pharmacists can have positive effects on the patient outcomes by recognizing patients’ symptoms and the toxicity of AEDs such as eye flickering, unsteady tremor, cognitive impairment, speech problems—all of which can be related and due to centrally active drugs,” said Bainbridge. The risk can increase “if the patient has too much drug on board and the drug level is too high for that person, or if he or she has a drug on the Beers criteria such as phenobarbital.”
A recent case–control study by Aaron S. Kesselheim, MD, JD, MPH, and colleagues published last year in JAMA Internal Medicine found that changes in the color of the AED tablet or capsule in the refill were associated with increased odds of nonpersistence and nonadherence to AED therapy, which may have serious medical, financial, and social consequences.
The JAMA Internal Medicine study was intriguing to pharmacists because it demonstrated that “patients actually do pay attention to the appearance of their medication, and if there is a discrepancy, they would delay in taking their medication until they can reach their physician or a pharmacist,” said Jack J. Chen, PharmD, Associate Professor in Neurology at Loma Linda University School of Pharmacy and Section Advisor for Neurology.
“My personal experience has been that the practice of informing patients of the changes in their medications is inconsistent,” Chen continued. “Pharmacists need to be more aware of medications used for neurologic conditions and become ready to provide thorough and consistent education to patients who take AEDs.”
Pharmacy computer systems can detect changes in product being dispensed based on NDC numbers and print warning labels for the prescription. Given that patients may not read those labels, however, taking a few seconds up front to explicitly tell them about the change in medication appearance during counseling can prevent significantly negative clinical outcomes for the patient. Pharmacy technicians can be trained to educate patients for this purpose.
Nonmotor symptoms of PD
Coming to the surface about PD now are its nonmotor symptoms, including orthostasis, anxiety, depression, gastrointestinal issues, and urinary symptoms. Nonmotor symptoms “have always been there. However, no one has really paid much attention to how common they are, and whether those symptoms are different between those who do and do not have PD,” Chen said.
“Specialists such as neurologists are very comfortable with motor-related features of PD, but pharmacists may have more knowledge regarding other medications to treat nonmotor symptoms,” Chen continued. From a medication therapy management (MTM) perspective, “there is an opportunity for pharmacists to help the patients with a more comprehensive approach to disease state management.”
Statins may be associated with an increase or decrease of PD incidence. Yen-Chieh Lee, MD, and colleagues recently published a study in Neurology suggesting that continued use of lipophilic statins in patients with dyslipidemia was associated with a lower incidence of new-onset PD compared with discontinuation of statin therapy, particularly in women and older patients. “It is premature to say that statins reduce the risk of PD because of a variety of confounders” present in the study, Chen said.
Statins and dementia
A recent systematic review by Karl Richardson, MD, and colleagues in the Annals of Internal Medicine disputed the association of cognitive decline and statins. It found that currently available evidence does not suggest an adverse effect of statin on cognition. The jury is still out on this, however. Bainbridge believes that “cognitive decline is associated with higher doses of statins” in older patients. “I make sure to screen my patients for that,” she said, “to decrease the dose.”