Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis

Abstract

This review summarizes Phase III clinical trial data available for fingolimod. The main purpose is to evaluate the benefit-risk profile of fingolimod, the first oral compound available for treatment of multiple sclerosis (MS) and just recently approved by the European authorities. The authors place this evaluation in the context of the known safety and efficacy profile of established compounds for therapy of MS to outline the current and future potential of fingolimod. The authors conclude that only long-term safety data from post-marketing surveillance plans, together with additional head-to-head studies, would allow evidence-based treatment decisions. Furthermore, risk-profile analyses including patient history, exposure data to certain pathogens, and genetic analyses may potentially help to choose the right drug for individual patients in the future. Until these approaches toward an individualized medicine have been validated, treatment decisions for one or the other compound will have to be based partly on class IV evidence. Therefore, a close dialog with the well-informed patient, secured by effective risk mitigation plans, is required to choose the compound.

Interferon β-Mediated Protective Functions of Microglia in Central Nervous System Autoimmunity

“…Until now, additional disease modifying and immunomodulatory therapies for RRMS have been licensed. Among those glatirameracetate [34], dimethyl fumarate [35], teriflunomide [36], fingolimod (Sphingosin-1-Phosphat receptor agonist) [37], and cladribine [38], as well as the humanized monoclonal antibodies Natalizumab, that inhibits lymphocyte migration into the CNS by blocking the adhesion molecule very late antigen-4 (VLA-4) [39], Alemtuzumab, that recognizes CD52 on lymphocytes resulting in T and B cell depletion [40,41], and Ocrelizumab, an anti-CD20 antibody specifically depleting B cells, have been approved [42]. Notably, beside its approval for RRMS, Ocrelizumab has been additionally licensed for treating PPMS.…”

FTY720 Markedly Increases Alloengraftment but Does Not Eliminate Host Anti-Donor T Cells that Cause Graft Rejection on Its Withdrawal

“…FTY is effective in promoting solid organ allograft survival and inhibiting autoimmune disease in various experimental animal models and recently has been approved for use in relapsing-remitting multiple sclerosis patients(1–3, 6, 11, 12). Studies by us and others indicate that FTY inhibits GVHD by multiple mechanisms without the abrogation of a graft-versus-leukemia (GVL) effect (13–16).…”