There are 4 approved drugs that bind to the sphingosine-1-phosphate (S1P) receptor fingolimod is one another is siponimod and then there is ozanimod and recently ponesimod…What’s the difference?
The receptor mediating the main effect on active MS is S1PR1
They all bind to this target and a few others. fingolimod hits S1P1,3,4,5, ponesimod is suggested to be S1P1-selective but it binds to others too (the lower the number the stronger the binding. This is the concentration needed to induce half maximal response. .
But important differences are how long they hang around for and this depends what happens when the drug is broken down.
Barry et al said the timing of severe relapses after stopping fingolimod appears somewhat predictable, with events occurring approximately within 2–4 months after stopping fingolimod. A review of the initial case reports noted that the relapses occurred between 4 and 16 weeks after stopping fingolimod. A separate review of cases with tumefactive lesions ranged in onset from 3 to 18 weeks after fingolimod cessation.
So if you are on fingolimod and want to have a baby and you are female and you stop fingolimod there is a risk of rebound/relapse in the study below about 60% of people had a relapse. However what will be the case with the other drugs.?
It could be much quicker woth ponesimod as the half live is a day and a half and cells can repopulate within a week, This is good if here is an adverse effect, and you want to stop, but it is possible that disease comes back. How quickly?
I would like to know it could be quick, meaning if you stop treatment you will suffer the consequences or you /your neuro needs a plan on how to switch to something else. On first look the half life of ozanimod is short and so disease reactivation could be very quick, but it is broken down to a molecule that is also active and one has a long half-life and so it takes time for white cells to return.
So as I have said when every you start a compounds you should also consider what you aim to do in the future and if having a family is the plan make sure you discuss this with your neuro/MS
Disease reactivation after fingolimod cessation in Multiple Sclerosis patients with pregnancy desire: A retrospective study. .Mult Scler Relat Disord. 2022 Jul 22;66:104066. doi: 10.1016/j.msard.2022.104066.
Reactivation of Multiple Sclerosis (MS) activity has been described after fingolimod cessation. Because of its contra indication during pregnancy, switch towards lower efficacy treatments are frequent in MS patients with childbearing desire but expose them to a risk of disease reactivation. In this retrospective study including 44 women with MS, a significant increase of the median annualized relapse rate was found in the year following fingolimod discontinuation compared to the period before (p < 0.0001), and 57% of women experienced at least one relapse. When considering to start fingolimod, particular attention should be paid to women with a short-term pregnancy desire.