Everything there is to know about Ponesimod (Ponvory®) and Fingolimod (Gilenya®)

What are sphingosine 1-posphate receptor modulators? 

Immunosuppressive drugs belonging to the family of sphingosine 1-phosphate receptor modulators are designed to reduce the number of lymphocytes (immune system cells) found in the blood. In people with multiple sclerosis, which is an autoimmune disease, lymphocytes attack the myelin sheath (the protective layer of neurons), causing damage to the neurons. By reducing the number of circulating lymphocytes, these treatments reduce neuron damage. 

Ponesimod has been on the market since 2021. However, the first sphingosine 1-phosphate receptor modulator to receive marketing authorisation for multiple sclerosis was fingolimod in 2010.

Fingolimod comes in capsules, while ponesimod comes in the form of tablets. Both are taken orally. 

A specific feature of ponesimod is that treatment is initiated according to a dose titration schedule, meaning that the dose is gradually increased until a maintenance dose is reached. It is very important to follow this titration schedule.

How should patients taking these treatments be monitored? 

Treatment with ponesimod and fingolimod must be taken under strict supervision by healthcare professionals. When one of these drugs is prescribed, patients and/or carers receive a guide or liaison booklet to ensure that they are properly informed. Patients of childbearing age should also be given a specific pregnancy card. Particular vigilance is required throughout the course of treatment. 

This type of treatment affects the immune system and therefore exposes patients to an increased risk of infection. Frequent blood tests must be carried out (blood count) to check for infection on a regular basis. In addition, if the patient's temperature rises above 38°C, or if flu-like symptoms appear while they are taking the treatment, it is important that they see a doctor as soon as possible, as these can be signs of a potential infection.

An electrocardiogram (ECG) should be taken before treatment is started, and any signs of dizziness, vertigo, nausea or palpitations should be reported to the doctor after the start of treatment.   

Patients should also pay attention to other aspects when taking ponesimod or fingolimod, such as monitoring their blood pressure and checking their eyesight. In the event of visual symptoms, you should inform your doctor immediately. The same applies to symptoms such as nausea, vomiting or stomachache, which may indicate liver failure. 

Any neurological changes such as sudden severe headaches or confusion should be reported to your doctor immediately.  

In addition, if ponesimod has been discontinued for 4 or more consecutive days without medical advice, you should see your doctor who will restart your treatment initiation schedule.

Sphingosine 1-phosphate receptor modulators increase the risk of skin cancer, so regular skin checks are recommended, especially for people with risk factors for skin cancer. It is also recommended to limit sun exposure by wearing protective clothing and regularly applying a sunscreen with a high sun protection factor (ideally SPF 50 or SPF 50 indicated on sunscreens). 

Patients can get all the necessary vaccines, and are even recommended to do so, as their immune defences are reduced (flu vaccine, Covid-19 or pneumococcal vaccine). The only vaccines that should be avoided are the so-called "live inert" vaccines, such as the yellow fever vaccine (required for travel to certain countries) or the BCG vaccine against tuberculosis or VZV (chickenpox virus). If this type of vaccine is required, treatment should be stopped 1 week before and for 4 weeks after receiving a live vaccine.

What are the contraindications to taking sphingosine 1-phosphate receptor modulators? 

These drugs should not be used in the following cases:

• Heart problems such as heart failure, heart rhythm disorders, a history of stroke or myocardial infarction, etc.; 
• Immunodeficiency (deficiency of the immune system);
• Moderate or severe liver failure; 
  
• Evolving cancer;
  
• Active infections;
  
• Pregnancy and women of childbearing age not using effective contraception.

What are the possible side effects? 

The most common side effects (affecting up to 10% of patients) that can develop after taking these treatments are as follows:

• Infections (urinary tract infections, viral respiratory infections such as bronchitis or pneumonia, etc.),
  
• headaches, backaches;
  
• flu;
  
• shingles;
  
• fever;
  
• cough;
  
• diarrhoea;
  
• vertigo and convulsions; 
  
• changes in vision due to an accumulation of fluid in the retina (back of the eye).

If patients taking ponesimod or fingolimod experience any of the above side effects, or any other symptoms that they think may be caused by their treatment, they should discuss them immediately with their doctor or pharmacist. They can also report the side-effects they experienced via the Yellow Card reporting site.