Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators.

INTRODUCTION: Sphingosine-1-phosphate (S1P) receptor modulators, of which one has received marketing approval and several others are in clinical development, display promising potential in the treatment of a spectrum of autoimmune diseases. AREAS COVERED: Administration of S1P1 receptor modulators leads to functional receptor antagonism triggering sustained inhibition of the egress of lymphocytes from lymphoid organs. First-dose administration is associated with transient cardiovascular effects. We compiled and discussed available pharmacokinetic, pharmacodynamic, and safety data of selective and non-selective S1P receptor modulators that were investigated in recent years. EXPERT OPINION: The safety profile of S1P receptor modulators is considered better than other classes of immunomodulators and was further improved by the development of up-titration regimens to mitigate first-dose effects. S1P receptor modulators display similar pharmacodynamic effects but have very different pharmacokinetic profiles. Drugs with a rapid elimination are of interest in case of opportunistic infections or pregnancy, whereas the need of re-initiation of up-titration in case of treatment interruption can present a challenge.