S1P Receptor Modulator Therapy Reversibility Considerations


Drs Jeffrey Dunn and Regina Berkovich provide insight into the biochemistry and reversibility of currently available S1P treatments for patients with multiple sclerosis.

Jeffrey Dunn, MD: You’ve mentioned reversibility first as we were discussing the immunomodulatory S1P modulators, those sphingosine 1-phosphate modulators. There are now 4 of those approved by the FDA for use in relapsing forms of multiple sclerosis in the US. Is there a differential in the reversibility profiles of those 4- S1P medications in that class?

Regina Berkovich, MD, PhD: Yes. And this is one of the immediate distinguishing factors that comes to mind.

Jeffrey Dunn, MD: Take us through that, how would you compare them then, 1 to 1?

Regina Berkovich, MD, PhD: Gladly. We have of course the very first medication that came, fingolimod. We all remember, because everyone had experience with this medication, and it was, overall, very successful, but we remember that for the lymphocytes to come back it usually takes about 6 weeks. And then, we have the next one, siponimod, and there it is shorter. Then we have the third, if we go chronologically, ozanimod. With that one we have slightly longer than with the fingolimod. Finally, we have ponesimod, which probably has the shortest period of time, that is, about 7 days, for the lymphocytes to come back.

Jeffrey Dunn, MD: A shorter span of reversibility seems like that may be favorable in managing patients on medications who are considering pregnancy. Is that your experience as well?

Regina Berkovich, MD, PhD: If we take the reversibility on lymphocytes as a marker for reversibility on other pharmacological functions of the drug, which by itself is somewhat of an agreement we have to make, then yes. Given the choices of those 4, if I have a patient who is planning to get pregnant or might find herself being pregnant, I would go with the last option, with the ponesimod, simply because of the as they say agility of it. The agility that I may have as a result of using it that I can change the course of treatment by discontinuing it at the time of pregnancy because I wouldn’t recommend stopping any disease modifying therapy until pregnancy actually takes place. This is one of the reasons probably the biggest one why I prefer to go with immunomodulatory medications and not with immunosuppressants because I prefer patients to get pregnant while on treatment.

Jeffrey Dunn, MD: There are so many considerations when it comes to choosing a therapy for someone who is pregnant or considering pregnancy. You would certainly advocate to our colleagues that reversibility really preconsidering an escape strategy prior to your first prescription is something you would recommend to them.

Regina Berkovich, MD, PhD: Correct. If we understand that statistically it’s important, never forget, that 50 percent of pregnancies are unexpected so we should not be catering for those 50% that are expected and forget about those unexpected pregnancies.

Transcript Edited for Clarity

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