New Therapies to Treat Multiple Sclerosis

Las Vegas—Patients with multiple sclerosis (MS) often suffer from relapses, creating a situation in which their disease progresses and disability worsens. The deteriorating condition also contributes to increased healthcare costs. To help patients and lower expenses, providers should initiate treatment soon after MS is detected, according to Bruce Cree, MD, PhD, assistant professor of clinical neurology at the University of California-San Francisco. Dr. Cree spoke at the Fall Managed Care Forum in a session titled Emerging Challenges on the Therapeutic Landscape of Multiple Sclerosis. Since last year, the US Food and Drug Administration (FDA) has approved new MS drugs, including fingolimod (the first oral medication for MS), dextromethorphan and quinidine, and dalfampridine. Older drugs reduce relapses by between 20% and 30%, but fingolimod reduces relapses by >50%, according to data Dr. Cree presented.

There are also several more drugs in the pipeline intended to treat MS, such as BG-12, teriflunomide, and laquinimod, which are all in phase 3 trials. “We are seeing a landscape change when it comes to MS therapies,” Dr. Cree said. The novel therapies may lead to a paradigm shift in dealing with a disease found in an estimated 2.5 million people worldwide and 400,000 in the United States. Most patients have bout-onset or relapsing-remitting MS. Three times as many women as men have MS, and the highest incidence is found in Caucasians. Dr. Cree said many people suffer from MS relapses that contribute to disability and “relentless deterioration of function 20 years after onset.” He added that the frequency of relapses varies, but they usually decline as time passes. Symptoms associated with MS include pain, depression, cognitive dysfunction, spasticity, and gait abnormalities.

Approximately 50% of patients with MS will die from causes associated with the disease, and MS shortens a person’s lifespan by an average of approximately 10 years. Dr. Cree discussed several trials examining the effect of certain drugs on annualized relapse rates. Patients treated with interferon beta-1b had a 31% reduction in relapse rates, those treated with interferon beta-1a had an 18% to 32% reduction in relapse rates, those treated with glatiramer acetate had a 29% reduction in relapse rates, and those treated with fingolimod had a 54% reduction in relapse rates. Relapses are costly, according to Dr. Cree. The total medical costs associated with a low-intensity episode are $243, a moderate-intensity episode costs $1847, and a high-intensity episode costs $12,870. Dr. Cree questioned the accepted method in most trials that defines progression as a 1-point change in the Expanded Disability Status Scale (EDSS), which is confirmed in 3 or 6 months. He said 50% of patients with a 1-point change who are confirmed at 3 months will improve to a lower EDSS by the end of the study compared with 33% of patients with a 1-point change confirmed at 6 months. However, Dr. Cree said neither measure is a good way to predict long-term disability.

Several studies have examined the costs associated with MS. However, because most of them are outdated, Dr. Cree said “we need an economic reanalysis” to gain a more accurate understanding of the costs. He cited studies that estimated the annual cost of MS in the United States was $13.6 billion (in 1994 dollars), the total lifetime costs per patient are $2.4 million (in 1994 dollars), and the mean annual costs per patient are $47,215 (in 2004 dollars). In addition, patients with MS have 2 to 3 times higher healthcare costs compared with those who do not have MS. One study found that 34% of MS costs are attributable to early retirement, 22% are attributable to disease-modifying therapies, and 10% are attributable to sick leave or reduced working time.

Another study examined the average wholesale price per year for numerous MS drugs: $38,475 for interferon beta-1b subcutaneously, $36,010 for interferon beta-1a intramuscular injection, $38,761 for interferon beta-1a subcutaneously, $40,187 for glatiramer acetate subcutaneously, and $48,000 for fingolimod orally. When treating patients with MS, Dr. Cree said some of the goals are reducing the frequency of relapses, slowing the progression of disability, maintaining adherence, and providing long-term efficacy and safety. He cited the National MS Society guidelines released in 2007 that therapy should be initiated as soon as possible following diagnosis; access to medications should not be limited by age, level of disability, or frequency of relapses; and patients should continue treatment until they experience a lack of benefit or intolerant adverse effects or better treatment becomes available.

New Treatment Options

Brian Steingo, MD, medical director at Neurologic Associates Research, discussed the new therapies available for MS patients. Before initiating treatment, he said that providers should compare benefits such as meaningful impact, disease course, and efficacy with risks such as potential safety issues. Dr. Steingo provided an overview of several trials of the MS drugs, including two, 24-month phase 3 studies involving laquinimod: ALLEGRO and BRAVO.

In ALLEGRO, patients were included if they were between 18 and 55 years of age, had relapsing-remitting MS, an EDSS score between 0 and 5.5, and disease characteristics. They were randomized to receive a daily 0.6-mg dose of laquinimod or placebo. The annualized relapse rate was 0.39 in the placebo group and 0.30 in the laquinimod group (P=.0024). The laquinimod group also had a significantly lower disability progression at 3 months (P=.012) and at 6 months (P=.002). In the BRAVO study, patients received a daily 0.6 mg dose of laquinimod with a matching oral placebo or a 30-mcg once-weekly interferon beta-1a intramuscular injection. Patients were included if they had relapsing remitting MS, were between 18 and 55 years of age, had an EDSS score between 0 and 5.5, and displayed disease characteristics. Exclusion criteria included a progressive form of MS, previous treatment with interferon beta-1a, interferon beta-1b, natalizumab, glatiramer acetate, or stem cell transplantation, or an onset of relapse between the screening and baseline visits. Patients in the laquinimod group had a significantly better relapse rate (P=.026) compared with the interferon beta-1a group, but there was no significant difference in sustained disability at 3 months or 6 months or in brain volume.

In September 2010, fingolimod became the first oral drug approved by the FDA to treat MS. Dr. Steingo discussed results of the 24-month, double-blind, randomized FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis) trial that compared once-daily doses of 0.50 mg fingolimod, 1.25 mg fingolimod, and placebo. At 24 months, the annualized relapse rate was 54% lower in the 0.5-mg fingolimod group and 60% lower in the 1.25-mg fingolimod group compared with placebo (P<.001 in both comparisons). Significantly fewer patients in the 0.5-mg fingolimod group and the 1.25-mg fingolimod group had EDSS progression compared with the placebo group (P=.03 and P=.01, respectively). Dr. Steingo also mentioned the TRANSFORMS (Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis) trial that compared 0.50 mg fingolimod, 1.25 mg fingolimod, and interferon beta-1a. At 12 months, the annualized relapse rate was 52% lower in the 0.5-mg fingolimod group and 38% lower in the 1.25-mg fingolimod group compared with placebo (P<.001 for both comparisons).