Oral Medications for Multiple Sclerosis

San Antonio—Until recently, patients with multiple sclerosis (MS) received treatment via subcutaneous or intramuscular injections or intravenous infusions. In the past 3 years, however, the FDA has approved 3 oral medications to treat the disease: fingolimod approved in September 2010, teriflunomide approved in September 2012, and dimethyl fumarate approved in March 2013.

At the AMCP meeting, a noted doctor and pharmacist discussed the treatment options and issues related to MS during a satellite symposium titled Evaluating the Cost-Benefit Equation for Oral Multiple Sclerosis Therapies. Genzyme supported the session with an educational grant.

Stephen Krieger, MD, director of the neurology residency program at Mount Sinai Medical Center in New York, said an estimated 350,000 to 400,000 people in the United States and 2.1 million people worldwide have MS. The disease, which in 75% of cases begins between 20 and 50 years of age, is the most common chronic disease affecting the central nervous system in young adults. Women are 3 times more likely than men to have MS.

MS Guidelines

Dr. Krieger said the guidelines for treating MS are nearly a decade old when the only approved drugs were interferon beta and glatiramer acetate. Despite the lack of guidance on prescribing oral drugs, he said it is important that MS is treated early and aggressively. Relapses can occur early in the disease and can lead to disability. However, Dr. Krieger said there is limited data on the long-term efficacy of disease modifying therapies because clinical trials usually last only 2 years, and the first drug to treat MS was not approved until 1993.

When deciding the drug to use, Dr. Krieger said healthcare professionals should not compare the results of different studies because they have different designs and protocols and do not include the same patients. Results can vary even when the same drug is tested. For instance, a trial found that patients taking fingolimod had a 55% reduction in gadolinium enhanced lesions, while another study indicated an 82% reduction in gadolinium enhanced lesions associated with fingolimod.

Instead, Dr. Krieger said more attention should be paid to trials that evaluate the drugs in a head-to-head setting, although there have not been any head-to-head studies comparing the oral MS medications. He added that the National Multiple Sclerosis Society recommends that healthcare professionals treat patients indefinitely unless there is a clear lack of benefit, intolerable side effects, or a better treatment option available.

When trying to determine a suboptimal response to medications, there are numerous options, including the number of relapses, the severity of relapses, the location of relapses, disability measures, and signs of lesions on a magnetic resonance imaging exam. However, Dr. Krieger said there are not many accurate ways to measure a sub-optimal response to MS drugs, so healthcare professionals should monitor patients and tailor the treatment to how they are reacting to the drugs.

“[MS] is not a 1 size fits all disease,” Dr. Krieger said.

Economic Considerations for MS

Jeffrey D. Dunn, PharmD, senior vice president at VRx Pharmacy Services, said MS is a lifelong disease state, progressive, and associated with a significant impact on disability. In fact, he said MS is the leading cause of disability in young women and the second leading cause of disability in young men in the United States.

It is also an expensive condition to treat. The annual health-related costs per patient with MS are $35,000, and the total cost to the US economy is $16 billion per year.

According to the Express Scripts 2010 Drug Trend report, MS treatments accounted for 22.9% of specialty spending under the pharmacy benefit, the second most expensive category behind inflammatory conditions. The per-member per-year specialty spend was $37.16 for inflammatory conditions and $29.80 for MS.

MS Treatment Compliance

Dr. Dunn added that there are issues with patients not taking MS medications as prescribed, discontinuing the drugs in the short-term, and a failure to continue the medications over the long-term because they do not realize the clinical benefit. Within 1 year of starting on MS drugs, 17% to 40% of patients stop taking them, according to Dr. Dunn. He said many patients who do not take the medications as prescribed cite a perceived lack of efficacy and adverse effects, including depression.

In a study of 798 patients who were not compliant with their injectable MS drugs, the most common reason patients gave for not using the medications is that they forgot to take them. Other explanations included that they did not feel like or were tired of taking the injections and that the dosing schedules were difficult and they experienced pain at the injection site.

Another reason for patients not taking their medications as prescribed is because they are being asked to pay for a higher share of the drug costs. Dr. Dunn cited the EMD Serono Specialty Digest 8th Edition that found the average copay for specialty drugs was $43 in 2009, $48 in 2010, and $54 in 2011. He expects the costs to continue to increase and predicts that 50% of spending in the pharmacy benefit will be on specialty medications, such as MS drugs.

With the high costs and lifelong disability associated with MS, Dr. Dunn said it is crucial that healthcare professionals educate patients about MS drugs. They also must understand if and why they are not adhering to the medications.

“We are investing a lot of money in these patients,” Dr. Dunn said. “We want to see the benefits.”

The National Multiple Sclerosis Society recommends that all FDA-approved therapies be included on formulations and that “failure to do so is unethical and discriminatory,” according to its disease management consensus statement. However, Dr. Dunn said payers should have closed formularies, although the lack of guidelines and data on MS drugs makes it difficult to assess what medications provide the best value or cost effectiveness. “It is a source of frustration,” he said.

Dr. Dunn said that managed care organizations are effective at analyzing randomized controlled trials and making formulary decisions, but most do not pay attention or follow up to see if the choices they made were correct. He added that they should also evaluate comparative effectiveness research in deciding what drugs to cover. “Benefit designs need to be addressed,” he said.