title: Multiple sclerosis therapeutic pipeline: opportunities and challenges.
abstract: The year 2010 marked the beginning of the era of oral medications for the treatment of multiple sclerosis, with the approval of dalfampridine to improve walking and fingolimod as the first oral disease-modifying agent. This review provides an overview of these and other emerging therapies, with an emphasis on the opportunities for new treatment paradigms they have the potential to offer, followed by a discussion of the challenges they will pose in the new era of multiple sclerosis management. Therapeutics in late-stage development for MS include non-selective immunosupressants, targeted immune-modulators, and monoclonal antibodies. Oral agents including cladribine, teriflunomide, laquinimod, and dimethyl fumarate, as well as monoclonal antibodies alemtuzumab, daclizumab, and rituximab are considered. Potential side effects and adverse event monitoring, including opportunistic infections, emergent malignancies, and other systemic consequences of immunosuppression are discussed in a unified section. Challenges of optimally staging, sequencing, and combining treatments in the expanding multiple sclerosis armamentarium are discussed. This review emphasizes the multifactorial decision making that these new therapeutics will warrant in terms of patient selection and personalization/individualization of therapy, and the increasingly interdisciplinary approach that will be necessitated by the new generation of agents.
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA. stephen.krieger@exchange.mssm.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Krieger
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000009:adverse effects; D000284:Administration, Oral; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D003221:Confusion / Q000139:chemically induced; D018450:Disease Progression; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008124:Locomotion / Q000187:drug effects*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D010348:Patient Care Team; D018579:Patient Selection; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D012720:Severity of Illness Index; D013110:Sphingosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D026902:Potassium Channel Blockers; D011409:Propylene Glycols; D015761:4-Aminopyridine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine