Siponimod

How it works

It selectively modulates S1P1 and S1P5 receptors, retaining lymphocytes within lymph nodes and so reducing the number of circulating lymphocytes available to enter the central nervous system.

Prescribing in practice

• CYP2C9 genotype must be determined before starting because patients homozygous for certain poor-metaboliser alleles are contraindicated and others require dose adjustment.
• It can cause bradycardia and atrioventricular conduction delay at initiation, so first-dose cardiac assessment is required in those with relevant cardiac history.
• It increases infection risk and necessitates checks of macular health, liver function and varicella immunity before treatment.

Monitoring

Monitor full blood count, liver function, blood pressure and, where indicated, cardiac rhythm at initiation and ophthalmological assessment for macular oedema.

Counselling the patient

• Report signs of infection, and remember that immune effects can persist for some weeks after stopping.
• Report any visual disturbance, which could indicate macular oedema.
• Effective contraception is needed during and for a period after treatment because of the risk to a developing baby.

Evidence & guidelines

Siponimod slowed disability progression in active secondary progressive multiple sclerosis in the randomised EXPAND trial and is recommended by NICE for eligible patients.