Heart features of fingolimod

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As we gear up for the mod wars as a number of S1P1 inhibitors arrive including siponimod and ozanimod, it will be interesting to see how fingolimod fairs. Fngolimod binds to S1P1, S1P3, S1P4 and S1P5 but the new variant bind to S1P1 and S1P5 and so avoid S1P3. This is in part the reason why fingolimod has heart issues and needs to be monitored. This risk is relatively low but needs to be checked. Will this mean that fingo gets chucked in the maggots pile once the others arrive, especially if they get first line statue in the UK?

Maybe things will be different if the patent on fingo expires, but the legal guys have kept it going and the shake up of 2019 as the patent expired in US didn’t happen, so we have to wait a few more years.

Cardiovascular autonomic individual profile of relapsing-remitting multiple sclerosis patients and risk of extending cardiac monitoring after first dose fingolimod. Vanoli E, Montano N, De Angelis G, Badilini F, Mirabella M, Bonavita S, Patti F, Bianco A, Sparaco M, Chisari C, Laroni A, Frigerio F, Bartezaghi M, Rossi S, Turrini R, Mancardi G.J Neurol Sci. 2019;405:116423.

Fingolimod exerts its therapeutic effect in multiple sclerosis by modulating sphingosine-1P receptors which are expressed in the heart mediating fingolimod first dose effects. Understanding potential interactions of baseline characteristics and autonomic profile with fingolimod first dose effects may add novel safety information and help explain cases requiring extension of the 6-hour ECG monitoring period. We aimed at characterizing the patient population treated with the first dose of fingolimod in clinical practice in an observational, multicenter, prospective 6-hours (up to 24) study. ECG was recorded for 15 min before first fingolimod administration and for 6 h after. Heart rate (HR) and HR variability in the frequency domain were derived from ECG traces. Out of the 625 enrolled patients, 580 (92.8%) were discharged at the sixth hour after fingolimod first dose; 45 (7.2%) required monitoring extension. Data confirm the well characterized cardiovascular fingolimod profile upon treatment initiation. Ten (1.6%) patients showed an atrioventricular block, all asymptomatic and self-resolving. Normalized spectral power in the High Frequency band (marking vagal modulation) and previous annualized relapse rate were independently correlated with the probability of undergoing extended monitoring. Our results could provide useful information for the stratification and individualized monitoring of MS patients prescribed with fingolimod.

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