title: Future clinical challenges in multiple sclerosis: Relevance to sphingosine 1-phosphate receptor modulator therapy.
abstract: The limitations of established therapies for multiple sclerosis (MS) are well-known and include the need for injections, treatment adherence and convenience issues, partial efficacy, and, in some cases, a risk of potentially life-threatening adverse events, such as progressive multifocal leukoencephalopathy. Recently, attention has focused on developing more effective therapies that are administered orally and target neurodegeneration as well as inflammation. In this review, we provide an outlook on the future clinical challenges for MS treatment and management, and focus specifically on the emerging sphingosine 1-phosphate receptor (S1PR) modulators. We highlight the importance of improving our understanding of the neurobiological basis of MS to develop well-tolerated targeted therapies and the need to include advanced MRI assessments that quantify neurodegeneration in interventional studies in MS. As more treatments become available, often with complex pharmacodynamic actions, objective assessment of benefit-to-risk profiles becomes increasingly important to ensure that patients receive appropriate care. Pharmacovigilance and immune monitoring will become important aspects of patient treatment and management in the future. With respect to S1PR modulation, we review the experimental agents that are in clinical development for MS and summarize the steps taken in postmarketing surveillance to ensure that fingolimod (FTY720) has a well-characterized safety profile.
authors.affiliation: Institute for Clinical Neuroimmunology, Munich, Germany. reinhard.hohlfeld@med.uni-muenchen.de
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Chris
authors.initials: C
authors.lastname: Polman
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000639:trends*; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D049349:Receptors, Lysosphingolipid / Q000276:immunology / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine