New Trials Testing Agents for Treating Relapsing-Remitting Multiple Sclerosis

DALLAS -- May 29, 2014 -- A plethora of new agents may soon be available for treating relapsing-remitting multiple sclerosis, according to information presented at the 2014 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Sixth Cooperative Meeting with Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Mitzi Joi Williams, MD, who is a neurologist at the MS Center of Atlanta, presented an overview current and investigational therapies for treating multiple sclerosis in a presentation titled “Relapsing Remitting MS: Current and Emerging Disease Modifying Therapies and Acute Relapse Management.”

Although there are more treatment options than ever before available to patients and clinicians, Williams said that new approaches are needed to treat acute exacerbations, as well as new options that can help meet the long-term goals of symptomatic management and rehabilitation.

She said an MS attack is defined by the development of neurologic symptoms likely caused by an inflammatory demyelinating lesion lasting at least 24 hours and supported by objective findings, often accompanied by repeated attacks of paroxysmal symptoms lasting at least 24 hours.

“We normally take a four-tiered approach to therapy for relapsing-remitting multiple sclerosis: acute therapy for exacerbations, disease-modifying therapy, symptomatic management, and rehabilitation,” said Williams.

According to Williams, it is easy to mistake an acute relapse in multiple sclerosis when a patient complains of new symptoms, but she said that often fever or other symptoms may be related to an infection.

She recommended treating acute relapse with steroids such as oral methylprednisolone, IV methylprednisolone, dexamethasone, or adrenocorticotropic hormone ACTH. “The late onset means that you don’t want to delay treatment,” she said.

Some patients treated with these agents may experience side effects such as insomnia, fluid retention, GI upset, and irritability.

There are currently 10 agents approved by the FDA for the treatment of multiple sclerosis that are indicated for treating clinically isolated syndrome and/or relapsing forms of the disease. The newer disease-modifying therapies include glatiramer acetate and the interferon beta agents. Available oral agents include fingolimod, dimethyl fumerate, and teriflunomide. Infusion therapies include natalizumab and mitoxantrone.

Williams noted that physicians may soon have additional options in their armamentarium, as alemtuzumab (a monoclonal antibody that binds to the CD52 protein) and pegylated interferon beta-1a have been submitted for FDA approval for the treatment of multiple sclerosis.

Results from two phase III studies (CARE-MS I and CARE-MS II) that compared alemtuzumab with interferon beta-1a in patients with relapsing-remitting multiple sclerosis showed that treatment with alemtuzumab was associated with significantly reduced relapse rates and sustained accumulation of disability.

Results from CARE-MS I indicated that treatment with alemtuzumab was associated with a insignificant 55% reduction in relapse; CARE-MS II found a 49% reduction in relapse rate over 2 years that was sustained in 42% of the study group.

Adverse events associated with treatment with alemtuzumab included profound lymphopenia, infections, and autoimmune thyroid disease.

In the phase III ADVANCE study, patients with relapsing multiple sclerosis were treated with pegylated interferon beta-1a 125 mcg SC every two or four weeks. The two-week dosing arm experienced a 35% decrease in relapses, a 67% reduction in new or enlarging T2 lesions, and a 86% decrease in Gd+ lesions. The four-week regimen produced a 27% decrease in relapses, a 28% reduction in new or enlarging T2 lesions, and a 36% decrease in Gd+ lesions.

Investigational agents that may be available down the road include daclizumab (a monoclonal antibody that binds to CD25), rituximab (a monoclonal antibody that binds to CD20), and ocrelizumab (an anti-CD20 monoclonal antibody). Phase II studies of daclizumab and ocrelizumab have shown treatment is associated with decreased annual relapse rates, reduced disability progression, and reductions in active lesions on MRI.

Adverse events from the daclizumab study indicated only mild effects, such as infusion-related diarrhea, increased risk of infection, and swelling.

Williams said that farther out, stem cell therapy, hormone therapy, and even personalized medicine may be promising areas of ongoing research.