Treating Progressive Multiple Sclerosis with Various Disease-Modifying Therapies

Physicians must consider a range of factors when initiating treatment with disease-modifying drug therapy and be prepared to switch to another first- or second-line option if the patient fails to respond.

At the 2013 annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Fifth Cooperative Meeting with Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held May 29-June 1 in Orlando, FL, Mark C. Cascione, MD, a neurologist and medical director of the South Tampa Multiple Sclerosis Center, presented an overview of multiple sclerosis disease state classifications, economic impacts, and experiences with a wide variety of disease-modifying therapies (DMT) to treat MS.

Though the first symptoms of MS include an initial loss of myelin or inflammation with a clinically isolated syndrome, Cascione said the hallmark feature of MS is an additional demyelination. Thereafter, increased disability indicates a progressive MS disease state.

Cascione pointed out that half of patients with relapsing-remitting MS (RRMS) will proceed to secondary progressive MS (SPMS) within 10 years of a post-MS diagnosis, while over 90 percent will transition to SPMS after 25 years.

According to Cascione, the financial burden of MS in the United States is approximately $28 billion per year in direct and indirect costs. The cost of care for each individual MS patient — not including drug charges — is approximately $18,000 per year, and that cost roughly doubles for every two-point increase in expanded disability status scale (EDSS) score. For example, an EDSS score of less than 2.5 costs approximately $5,000 cost per year, while an EDSS score of 8.0 costs approximately $46,000 per year. Though an MS patient with an EDSS score of 2.0 is minimally disabled, Cascione said a patient with an EDSS score of 8.0 is typically restricted to bed, but he or she may be out of the bed for extended periods of time and capable of self-care functions.

In utilizing steroids to treat MS, Cascione said methylpredinisolone administered intravenously (IVMP) has been the most common steroid used. Clinical trials of IVMP in 457 MS patients with optic neuritis revealed a decrease in visual field and optic field but not visual acuity six months after treatment. However, all of those benefits had disappeared at 12 months post-treatment. Cascione noted that after IVMP therapy, it’s particularly important to carefully monitor the patient’s glucose levels and other symptoms, since the adrenals generally shut down after treatment.

Briefly comparing and contrasting a variety of other treatments for RRMS, Cascione said Acthar gel, an animal-derived gel form of adrenocorticotropic hormone (ACTH), can be effective in treating patients with poor intravenous access, but he noted it’s expensive. For RRMS patients that are refractory to steroids, intravenous immunoglobulin therapy (IVIT) is also an option, as a recent randomized clinical trial involving 24 IVIT-treated patients compared to 23 IVMP-treated patients resulted in data suggesting that IVIT may be superior to IVMP.

While DMTs are evaluated on the basis of relapse frequency, lesion frequency detected by MRI, and effects on progression of disability measured by EDSS scores, Cascione urged MS physicians to remember that clinical studies of DMTs are not directly comparable between separate independent studies, so only studies that directly compare DMTs should be considered in weighing the efficacy of one individual DMT over another.

With roughly 10 different FDA-approved DMTs currently available for use in MS patients, Cascione said there’s a significant amount of attention being devoted to switching DMTs in challenging patients. In examining interferon, fingolimod, teriflunomide, dimethyl fumarate, natalizumab, and mitoxantrone, Cascione said dimethyl fumarate has exhibited the fewest number of side effects, and the flushing response can be simply managed with aspirin or eating a fatty meal prior to administration. In contrast, mitoxantrone may have the most severe side effects, but it’s the only FDA-approved drug for the treatment of progressive MS, and it may be the most effective in more severe forms of the disease.

Nevertheless, as more treatments for multiple sclerosis gain FDA approval, Cascione said switching DMTs will become an increasingly important part of progressive MS therapy.