Since the approval of
fingolimod, several selective
sphingosine-1-phosphate receptor modulators have entered clinical development for
multiple sclerosis. However, side effects can occur with
sphingosine-1-phosphate receptor modulators. By considering short-term data across the
drug class and longer term
fingolimod data, we aim to highlight the potential of
sphingosine-1-phosphate receptor modulators in
multiple sclerosis, while offering reassurance that their benefit-risk profiles are suitable for long-term
therapy. Short-term
fingolimod studies demonstrated the efficacy of this
drug class, showed that
cardiac events upon first-dose administration are transient and manageable, and showed that serious adverse events are rare. Early-phase studies of selective
sphingosine-1-phosphate receptor modulators also show efficacy with a similar or improved safety profile, and treatment initiation effects were reduced with dose titration. Longer term
fingolimod studies demonstrated sustained efficacy and raised no new safety concerns, with no increases in
macular edema,
infection, or
malignancy rates. Switch studies identified no safety concerns and greater patient satisfaction and persistence with
fingolimod when switching from
injectable therapies with no washout period. Better outcomes were seen with short than with long washouts when switching from
natalizumab. The specific immunomodulatory effects of
sphingosine-1-phosphate receptor modulators are consistent with the low observed rates of long-term,
drug-related adverse effects with
fingolimod. Short-term data for selective
sphingosine-1-phosphate receptor modulators support their potential effectiveness in
multiple sclerosis, and improved side-effect profiles may widen patient access to this
drug class. The long-term safety, tolerability, and persistence profiles of
fingolimod should reassure clinicians that
sphingosine-1-phosphate receptor modulators are likely to be suitable for the long-term treatment of
multiple sclerosis.