Assessing New Treatment Options for MS

Tampa—Since 2010, the FDA has approved 3 oral drugs—fingolimod, teriflunomide, and dimethyl fumarate—to treat patients with multiple sclerosis (MS). Results from phase 3 trials indicated the new medications were superior to older options, according to Jacquelyn Bainbridge, PharmD, professor, University of Colorado.

“The newer agents won,” said Dr. Bainbridge, who spoke during a satellite symposium at the AMCP meeting. “That is the bottom line.” This satellite symposium was supported by educational grants from Biogen Idec and Teva Neuroscience.

Still, Dr. Bainbridge and Sheldon Rich, RPh, PhD, said there are challenges to treating the disease. The medications are expensive, there is no blood test or cure for the disease, the causes of MS are not fully understood, and patients do not always adhere to the treatment regimens.

Dr. Bainbridge defined MS as a chronic inflammatory disease characterized by myelin destruction and axonal damage. More than 2.7 million people worldwide and 400,000 Americans have MS, which is the second most common cause of neurologic disability in the United States. Each week, 200 new cases of MS are diagnosed in the United States, and 80% of patients develop the disease between 16 and 45 years of age.

Health-related costs associated with MS are more than $45,000 per year. If the disease is untreated, a person’s life span is decreased by an average of 5 years, while 50% of patients require a cane or more support for ambulation within 10 years of onset and 30% will become wheelchair or bed bound.

Treatment Options

Early, aggressive treatment is important, according to Dr. Bainbridge, because relapses are most common shortly after disease onset and decrease over time. She said people typically have spinal cord and brain issues before realizing they have MS. Magnetic resonance imaging (MRI) exams are effective at predicting relapses, disease activity, and long-term disability. “MRIs are our right hand friend for [MS],” Dr. Bainbridge said.

After diagnosing MS, healthcare professionals have several treatment options. The older treatments are self-injectable medications, such as glatiramer acetate, intramuscular and subcutaneous interferon beta-1a, and interferon beta-1b. The newer treatments are natalizumab (an intravenous infusion drug approved in 2010) as well as the 3 oral drugs (fingolimod, teriflunomide, and dimethyl fumarate), which were approved in 2010, 2012, and 2013, respectively.

There are also a few MS drugs in late-stage development, including daclizumab (subcutaneous), ocrelizumab (intravenous infusion), laquinimod (oral), and pegylated interferon beta-1a. In late December 2013, the FDA rejected the approval of alemtuzumab for MS. Genzyme, the drug’s manufacturer, is appealing the FDA’s decision. In addition, 70 doctors involved in alemtuzumab’s clinical trials published a letter in Lancet urging the FDA to approve the drug, while patient advocates are also asking the FDA to make the drug available.

Managed Care Implications

Dr. Rich, president, SJR Associates, LLC, adjunct clinical professor, University of Michigan and Wayne State University, encouraged a multidisciplinary approach to treating MS and said pharmacists could play a major role working with physicians and other providers.

By providing medication therapy management services, pharmacists can educate patients about their treatment options, provide them with realistic expectations regarding treatment effects, and help them with side effects, costs, comorbid conditions, and other barriers to health improvements. Patients benefit from medication therapy management by having a slower disease progression, fewer and less severe symptoms, and improvements in work productivity.

Dr. Rich said cognitive impairment, not physical impairment, is the top reason for disability in patients with MS. He added that there are 10 disease-modifying therapies for MS with 7 mechanisms of action available to help improve cognitive and physical abilities. The goals of treatment regimens include decreasing clinical attacks, reducing the development of sustained disability, and preventing silent MRI lesions.

Treating MS early can have numerous benefits, according to Dr. Rich, including decreasing mortality and delaying or preventing the transition to secondary progressive disease.

There are advantages and disadvantages of the treatment options, according to Dr. Rich. Glatiramer acetate, interferon beta-1b, and interferon beta-1a have been approved for more than 20 years, so they have known efficacy and safety profiles and long-term data. However, the disadvantages include that they are injections and are associated with injection site problems. The interferon products are also associated with flu-like symptoms, while glatiramer acetate is associated with immediate post-injection reaction.

The advantages of natalizumab and mitoxantrone include less frequent dosing and guaranteed adherence. However, mitoxantrone is rarely used in the United States because of an increased incidence of cardiotoxicity and high occurrences of leukemias. There is also a risk of progressive multifocal leukoencephalopathy in patients who take natalizumab, although Dr. Rich said the drug is nonetheless well tolerated.

As of now, there are no biomarkers available to help patients and providers choose the most appropriate medications, so they assess efficacy, safety, tolerability, costs, route of administration, and other factors.

Medication Adherence

Dr. Rich noted that adherence rates with the injectable drugs are approximately 50%. Patients are more likely to take oral drugs, but the medications are new and do not have long-term data available. If patients do not adhere to their regimens, Dr. Rich said they have more relapses and disability. Common reasons for nonadherence include forgetting to take their medicine, a perceived lack of efficacy, and safety concerns.

If MS is untreated, relapses occur every 6 months on average, according to Dr. Rich. If the disease is treated, relapses typically occur every 2 to 5 years. Pointing out that adherence leads to fewer relapses “really resonates with patients,” according to Dr. Rich.

He added that adherence to medications is directly correlated with decreased symptomatic problems, increased quality of life, decreased healthcare-related expenses, and continued employment. To improve adherence, Dr. Rich suggested involving family members and caregivers and simplifying treatment regimens with a preference toward once-daily regimens and monotherapies. He also said healthcare professionals should let patients know that MS medications only work if patients take them, they do not cure the disease, and they may not eliminate symptoms or future disease activity.

Payers can also influence drug utilization, according to Dr. Rich. Some examples of interventions include step therapy, prior authorization, automated controls, and differential tiering. When making formulary decisions, payers should consider numerous factors, such as safety, efficacy, cost-effectiveness, discounts, rebates, physician support, budget impact, and contracts with pharmacy benefit managers, physicians, and pharmacists.