S1P Receptor Modulators

Sphingosine 1‑phosphate (S1P) receptor modulators are a newer class of oral medicines for moderate to severe ulcerative colitis. The two drugs currently approved in the United States are ozanimod and etrasimod. They work by trapping certain white blood cells in lymph nodes, which reduces gut inflammation but also affects the heart and eyes, so careful monitoring is important before and during treatment. (pubmed.ncbi.nlm.nih.gov)

Key Takeaways

• Ozanimod (Zeposia) and etrasimod (Velsipity) are once‑daily oral S1P receptor modulators for adults with moderately to severely active ulcerative colitis. (drugs.com)

• Both drugs lower circulating lymphocyte (white blood cell) counts by roughly half, which helps control inflammation but slightly increases infection risk. (pfizermedical.com)

• S1P receptors are also present in heart tissue, so baseline heart checks and, in some people, monitored first doses are recommended. (drugs.com)

• Both medicines can rarely cause macular edema, a swelling in the center of the retina, so eye exams and prompt reporting of vision changes are important. (drugs.com)

• As of late 2025, ozanimod and etrasimod are approved for ulcerative colitis, not for Crohn’s disease, where trials have shown mixed results. (pubmed.ncbi.nlm.nih.gov)

What are S1P receptor modulators?

S1P receptor modulators are small‑molecule medicines that act on sphingosine‑1‑phosphate receptors found on lymphocytes and other cells.

By binding to specific S1P receptor subtypes, they cause lymphocytes to remain in lymph nodes instead of circulating in the blood and reaching inflamed gut tissue. This reduces immune attack in the colon while preserving many normal immune functions. (news.bms.com)

In large trials, S1P modulators improved remission and mucosal healing rates in ulcerative colitis when used for both induction and maintenance therapy compared with placebo. (pubmed.ncbi.nlm.nih.gov)

Where do ozanimod and etrasimod fit in treatment?

Both agents are used for moderately to severely active ulcerative colitis in adults. They are usually considered when 5‑ASA drugs are not enough and may be used before or after biologics, depending on local guidelines, prior treatments, and individual risk factors. (pubmed.ncbi.nlm.nih.gov)

As of November 2025, neither medicine is approved for Crohn’s disease in the United States. Phase 3 Crohn’s trials have had mixed or negative results, so use in Crohn’s remains investigational. (pubmed.ncbi.nlm.nih.gov)

Ozanimod vs etrasimod at a glance

Both medicines share class effects, including lymphopenia, infection risk, blood pressure increases, and rare eye or heart issues, but their receptor selectivity, titration needs, and interaction profiles differ slightly. (mdpi.com)

How these medicines affect the heart

Why heart monitoring is needed

S1P₁ receptors help regulate heart‑rate and electrical conduction. When an S1P modulator is started, there can be a transient slowing of the heart rate and a small risk of atrioventricular (AV) conduction delays, particularly on the first day of treatment. (pubmed.ncbi.nlm.nih.gov)

In ulcerative colitis trials:

• Average first‑day heart‑rate drops were small, often under 10 beats per minute.

• A small percentage of participants had bradycardia or first‑degree AV block, usually mild and resolving without stopping the drug. (pmc.ncbi.nlm.nih.gov)

Baseline heart checks for everyone

Before starting ozanimod or etrasimod, labels recommend several steps: (drugs.com)

• Heart history review
  Recent heart attack, unstable angina, stroke, decompensated heart failure, or certain rhythm problems are formal contraindications, unless a pacemaker is in place. (drugs.com)

• Electrocardiogram (ECG)
  An ECG is recommended for all patients to look for slow baseline heart rate, AV block, long QT interval, or other conduction problems.

• Medication review
  Special caution is needed with drugs that also slow heart rate or affect conduction, such as some beta‑blockers, certain calcium‑channel blockers, and class I or III antiarrhythmics.

• Blood pressure check
  Both drugs can cause a modest rise in blood pressure over time, so baseline values and regular checks are advised. (zeposia.com)

First‑dose monitoring in higher‑risk patients

For most people with a normal ECG and no significant cardiac history, ozanimod uses its 7‑day titration pack to limit the heart‑rate drop and does not require routine in‑clinic first‑dose monitoring. (zeposiahcp.com)

For people with certain risk factors, such as:

• Resting heart rate below about 55 beats per minute

• Mild pre‑existing AV block

• History of significant heart disease or uncontrolled high blood pressure

cardiology input and first‑dose observation for several hours may be recommended, with repeated vital signs and ECG checks. Similar guidance exists for etrasimod, which does not have titration but still carries a small, early heart‑rate effect. (pmc.ncbi.nlm.nih.gov)

Ongoing care teams usually continue to monitor blood pressure and ask about symptoms such as dizziness, fainting, chest pain, or new palpitations at follow‑up visits.

Eye safety and macular edema

What is macular edema?

The macula is the central part of the retina that controls sharp, detailed vision. S1P modulators have been linked to rare cases of macular edema, where fluid builds up in this area and can damage vision if not treated. (drugs.com)

Risk appears higher in people with:

• Diabetes

• A history of uveitis or other eye inflammation

Recommended eye monitoring

Guidance from product information includes: (drugs.com)

• Before or soon after starting therapy

• For ozanimod, an eye exam is recommended, especially for anyone with diabetes or past uveitis, including a view of the fundus and macula.

• For etrasimod, labels recommend a fundus exam, including the macula, near treatment start for all patients.

• During treatment
  Periodic eye examinations are suggested, particularly in higher‑risk groups, and urgently any time new visual symptoms arise.

Vision symptoms that need quick attention

Patients on S1P modulators should be reviewed promptly if they develop:

• Blurry or wavy central vision

• New blind spot or dark patch in the center of vision

• Unusual color vision or increased light sensitivity

These features can signal macular edema and should trigger an ophthalmology exam and review of ongoing S1P therapy. (drugs.com)

Other important monitoring

Although this article focuses on heart and eye issues, several other safety checks are standard.

• Blood counts and infection risk
  Both drugs lower circulating lymphocytes by about 45–55 percent, which can increase susceptibility to infections. Labels recommend a recent complete blood count before starting, periodic checks during therapy, and delayed initiation if there is an active infection. (pfizermedical.com)

• Liver tests
  Elevations in liver enzymes are seen in a minority of patients. Baseline liver function tests and periodic re‑checks are advised, especially if symptoms such as jaundice, dark urine, or unexplained fatigue appear. (drugs.com)

• Blood pressure and lung function
  Modest average increases in blood pressure are reported with both agents, so repeated monitoring is recommended. Ozanimod can also slightly reduce lung function in some people, so spirometry may be used if respiratory symptoms develop. (zeposia.com)

• Pregnancy and contraception
  Animal data suggest fetal risk for both medicines, so product labels advise avoiding use in pregnancy and using effective contraception during treatment and for a period after stopping (longer for ozanimod than for etrasimod). (pfizermedical.com)

FAQs

Are S1P receptor modulators “stronger” or “weaker” than biologics?

Trials suggest that ozanimod and etrasimod have meaningful efficacy for induction and maintenance of remission in ulcerative colitis, including endoscopic and histologic healing, but direct head‑to‑head comparisons with biologics are limited. (pubmed.ncbi.nlm.nih.gov)
Choice between a biologic, a JAK inhibitor, or an S1P modulator usually depends on prior drug history, comorbidities, risk tolerance, and patient preferences for oral pills versus injections or infusions.

Who might be a typical candidate for ozanimod or etrasimod?

Common candidates include adults with moderate to severe ulcerative colitis who prefer an oral advanced therapy, have no major uncontrolled heart disease or serious eye disease, and either have not responded to or cannot tolerate conventional therapies. Final decisions are individualized by the gastroenterology team, often with cardiology or ophthalmology input when risk factors are present.

How long are heart and eye checks continued?

Heart‑related monitoring, such as blood pressure and symptom review, continues throughout treatment, while ECGs are often repeated if cardiac risk changes or the medicine is stopped and restarted. Eye exams are typically done near treatment start, then periodically or any time vision changes occur, since macular edema can arise later during therapy as well as early on.