Immunomodulatory therapies for relapsing-remitting multiple sclerosis: monoclonal antibodies, currently approved and in testing

Abstract

Relapsing–remitting multiple sclerosis (RRMS), a CNS inflammatory demyelinating disease, is one of the most prevalent causes of chronic disability in young adults. Studies of the disease pathogenesis have identified multiple therapeutic targets. The number of approved disease modifying therapies has almost doubled within the past 5 years, which creates a challenge for medical professionals to stay abreast of their use in everyday practice. This manuscript provides an overview of available injectable, oral, and intravenous therapies for RRMS, and offers guidance in selecting an appropriate therapy. Focus is on the recently approved and emerging monoclonal antibody therapies, because they offer more selective and superior therapeutic efficacy compared with injectable and oral disease modifying therapies. We discuss the outlook for monoclonal antibodies and their role in RRMS treatment in the future.

Keywords:

• alemtuzumab
• daclizumab
• mechanism of action
• monoclonal antibody
• natalizumab
• ocrelizumab
• ofatumamab
• relapsing remitting multiple sclerosis

Acknowledgements

We thank C. Zelasky for critical reading of the manuscript.

Financial & competing interests disclosure

S Markovic-Plese has received research grants from Genzyme Inc, Biogen Idec, EMD Serono and clinical trial support from Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The number of approved therapies for the treatment of relapsing–remitting multiple sclerosis has doubled within the past 5 years.

• The newly approved monoclonal antibodies offer more selectivity and have superior therapeutic efficacy.

• The most recently approved monoclonal antibody, alemtuzumab, offers superior efficacy and treatment may provide long-lasting disease suppression.

• In selecting a disease-modifying therapy, one most consider efficacy, safety, and tolerability of the drug while keeping in mind each individual patients preferences.

• The first-line agents continue to be the injectables (interferons and glatiramer acetate) and oral therapies (fingolimod, teriflunomide, and dimethyl fumarate) with their superior safety and tolerability profiles and are indicated in patients with mild to moderate disease activity.

• Second-line agents include mitoxantrone and the monoclonal antibodies with their superior efficacy but increased side effect profiles, they are recommended for aggressive disease or if other therapies have failed.

• The future of monoclonal antibodies is promising with their ability to selectively inhibit key molecular targets and preserve the immune response against infections.

• The use of monoclonal antibodies is expanding and expected to make significant contributions to the treatment and study of multiple sclerosis in the next 5–10 years.