S1P receptor modulators are multiple sclerosis (MS) disease-modifying drugs you take as a pill. They’re used to treat relapsing MS (RMS) by reducing the number of immune cells called lymphocytes in the blood. This lowers the amount of damage to your brain and spinal cord.
How Do S1P Receptor Modulators Work?
S1P receptor modulators help stabilize or “tighten” the blood-brain barrier, the membrane that surrounds your brain and spinal cord and protects it from disease. This barrier regulates what comes in and out of the space around the brain and spinal cord.
In order to cause damage to your myelin, immune cells (such as T cells and B cells) have to be able to cross that border. Because S1P receptor modulators prevent that, inflammation goes down and you have less damage to your cells.
S1P receptor modulators also interfere with the movement of these immune cells out of lymph nodes so they can’t cross into the central nervous system, essentially “trapping” them inside. This helps reduce the damage to brain and spinal cells.
Which S1P Receptor Modulators Are Used to Treat Relapsing MS?
Four S1P receptor modulators are FDA approved to treat relapsing MS:
Fingolimod (Gilenya, Tascenso ODT) is the only option that’s FDA-approved for children. Doctors can prescribe it to kids aged 10 and older.
When Are S1P Receptor Modulators Prescribed for Relapsing MS?
S1P receptor modulators are FDA-approved to treat relapsing forms of MS. This includes:
- Relapsing-remitting MS
- Secondary progressive MS
- Clinically isolated syndrome
If you or your loved one is under 18, fingolimod (Gilenya, Tascenso ODT) is an option for treatment.
How Do You Take S1P Receptor Modulators?
S1P receptor modulators are oral medications you take by mouth. They come in either tablet or capsule form. You take one dose a day.
For every S1P receptor modulator except for fingolimod, you’ll start on a lower dose than you’ll ultimately take in the long run. This helps your body get used to the mediation and lower chances of side effects. Your doctor will talk to you about your dosing schedule to be sure you understand how to “ramp up” to your regular dose.
Your doctor may monitor you closely for your first dose to watch for certain side effects. You should be able to take your S1P receptor modulator with or without food.
How Effective Are S1P Receptor Modulators?
Studies show S1P receptor modulators decrease MS relapse rates and may slightly delay disease progression in people with relapsing MS.
In adult MS registrational trials of the different S1P receptor modulators, researchers found each drug to have different levels of success in reducing the number of relapses per year, also called annualized relapse rate (ARR).
Are S1P Receptor Modulators Safe?
Doctors consider these treatments safe for treating MS. As with most medications, there are risks of rare adverse events. These risks are slightly higher if you take fingolimod (Gilenya, Tascenso ODT) than with other S1P receptor modulators.
They include risk of:
- Cancer
- Decreased lung function
- Fluid buildup in the eye (macular edema)
- High blood pressure (hypertension)
- Slowed heart rate (bradycardia)
You should avoid live vaccines while you’re taking an S1P receptor modulator. Also avoid them for one month (siponimod), two months (fingolimod), or three months (ozanimod) after you stop taking an S1P receptor modulator.
A rare but serious reaction to S1P receptor modulators is progressive multifocal leukoencephalopathy (PML), a brain infection that can cause death. Your doctor can test you for a certain virus to see if you’re at a higher risk of getting this reaction.
To reduce your risk of getting a serious side effect, your doctor may give you certain tests before starting you on an S1P receptor modulator. These include:
- Complete blood count (CBC)
- Electrocardiogram (EKG)
- Liver function tests (LFTs)
- Varicella-zoster IgG antibody testing (VZV) and VZV vaccination if antibody-negative
- Eye tests to screen for fluid buildup in eyes
- Gene testing (for siponimod only)
- Skin exam
Your doctor may repeat some of these tests as you start your treatment.
What Are the Common Side Effects of S1P Receptor Modulators?
It’s common for S1P receptor modulators to cause:
- Changes in liver function
- Diarrhea
- Headache
- High blood pressure
- Increased infection risk
- Slowed heart rate
- Upper respiratory infections
Who Should Not Take S1P Receptor Modulators?
If you’ve had a heart event in the last six months such as a heart attack (myocardial infarction), unstable angina, stroke, transient ischemic attack, or heart failure requiring hospitalization, you shouldn’t take an S1P receptor modulator.
You raise your risk of an adverse reaction if you take an S1P receptor modulators while also living with:
- Asthma
- Chronic obstructive pulmonary disease
- Diabetes
- Pulmonary fibrosis
- Uveitis (inflammatory disease of the eye)
If you take a monoamine oxidase inhibitor for depression or have obstructive sleep apnea, ozanimod (Zeposia) isn’t a good choice for you.
People who take certain drugs should take caution before using S1P receptor modulators. These drugs include:
- Some cancer drugs, such as antineoplastics, immunomodulating drugs, and non-corticosteroid immunosuppressive therapies
- Drugs to treat abnormal heart rhythms
- Beta-blockers or calcium channel blockers
If you take warfarin, an anticoagulant drug used to prevent blood clots, an S1P receptor modulator may affect the way it works in your body. Talk to your doctor about whether this treatment choice is best for you.
How Much Do S1P Receptor Modulators Cost?
Prices for S1P receptor modulators vary. It’s unlikely you’ll pay the full retail cost. These range from:
- Fingolimod (Gilenya, Tascenso ODT) $11,105; price with coupon $2,327
- Ozanimod (Zeposia); $8,297; no coupon available
- Ponesimod (Ponvory) $20,106; price with coupon $9,819
- Siponimod (Mayzent) $17,020; price with coupon $9,851
With a manufacturer’s coupon, your cost could be as little as $0. These manufacturers provide assistance:
Fingolimod (Gilenya) does not offer program assistance.
Clinical Trials of S1P Receptor Modulators for Relapsing MS
Clinical trials are how doctors are able to create new treatments for MS. To do this, they need volunteers with MS to take part.
A clinical trial may be an option for you if:
- Traditional treatments aren’t working for you.
- You’re interested in learning more about new therapies.
- You’d like to be part of research that could help others who live with MS.
If you’re interested in joining a clinical trial:
Talk to your doctor. They may know of trials that you’d be right for because of your personal MS course.
Search a clinical trial database. Websites like ClinicalTrials.gov list all ongoing clinical trials. You can search by condition, location, treatment stage, and more.
Join a MS patient registry. These groups collect information about people with MS and help match volunteers with clinical trials. Some are sponsored by government agencies. Others are run by hospitals, nonprofits, or private companies. Do your research and find one that works for you.
What to Know if You’re a Caregiver
Helping your loved one take an S1P receptor modulator won’t be hard because of the way they take it, but the timing in the beginning can be complicated for some of these medications.
Go over the schedule with the doctor so you also understand it and can help keep your loved one on track.
Make sure you also know which side effects to watch for, like signs of depression or breathing issues.
Is an S1P Receptor Modulator Right for Me?
You’re gathering the info you need to make an informed decision about your MS treatment. Organize your thoughts with these factors in mind:
How you'll take your medicine
Because they’re tablets or capsules, S1P receptor modulators are easy to take, but some of them require titration, or “ramping up” of the dose that requires a very specific dosing schedule.
Prior treatments
If you’ve tried other DMTs, like infusions, and they haven’t worked or are hard to manage, S1P receptor modulators may be a better option.
Potential side effects
The side effects of S1P receptor modulators can be mild or more serious. The most common are diarrhea, headache, high blood pressure, and upper respiratory infections. You’re also at risk of some less common but more serious effects such as liver damage, cancer, fluid buildup in the eye, and PML.
Costs
S1P receptor modulators can cost a lot. Be sure you have all the information you need to make a smart decision about their affordability. Insurance may help, especially governmental insurance like Medicare and Medicaid. You can also use copay cards or manufacturer assistance programs to help lower or even eliminate the cost.
Medical history and related conditions
If you’re pregnant, planning to get pregnant, or breastfeeding, talk to your doctor before taking an S1P receptor modulator. Doctors typically do not recommend you take these treatments during these time periods. Having certain heart and lung conditions may also rule out S1P receptor modulators for you.