S1P Receptor Modulators

Sphingosine-1-phosphate (S1P) receptor modulators are oral medicines that lower gut inflammation by trapping certain white blood cells in lymph nodes. In IBD care, two options are available for adults with moderate to severe ulcerative colitis: ozanimod and etrasimod. Both can help induce and maintain remission, but they require specific heart and eye checks before and during treatment to stay safe. (drugs.com)

Key takeaways

• Ozanimod and etrasimod are oral therapies for moderate to severe ulcerative colitis, not approved for Crohn’s disease in the U.S. as of November 7, 2025. (fda.gov)

• They keep lymphocytes from leaving lymph nodes, which reduces immune traffic to the intestines. (drugs.com)

• Heart checks are required: baseline ECG for both, and care with drugs that slow heart rate or affect heart rhythm. (drugs.com)

• Eye checks are required: baseline exam of the back of the eye, including the macula, and periodic follow‑up. (dailymed.nlm.nih.gov)

• Vaccine timing matters: avoid live vaccines during therapy and for about 5 weeks after etrasimod and 3 months after ozanimod. (dailymed.nlm.nih.gov)

How S1P modulators work

• S1P receptors sit on lymphocytes. When blocked, lymphocytes stay inside lymph nodes rather than circulating to inflamed gut tissue.

• Ozanimod targets S1P1 and S1P5. Etrasimod targets S1P1, S1P4, and S1P5. The clinical effect is a drop in circulating lymphocytes, which is reversible after stopping the drug. (drugs.com)

When they are used

• Both drugs are FDA‑approved for adults with moderately to severely active ulcerative colitis. They can be used to induce remission and to maintain it.

• As of November 2025, neither drug is FDA‑approved for Crohn’s disease. Ozanimod did not meet the primary endpoint in a Crohn’s phase 3 trial. (fda.gov)

Dosing at a glance

• Ozanimod: start with a 7‑day titration pack to reduce early heart‑rate slowing, then 0.92 mg once daily. In mild or moderate liver impairment, the maintenance dose is every other day. (drugs.com)

• Etrasimod: 2 mg once daily, no titration needed. (dailymed.nlm.nih.gov)

Symptom improvement is often assessed by week 10 for ozanimod and week 12 for etrasimod in the pivotal trials, with maintenance benefits seen at one year. (pubmed.ncbi.nlm.nih.gov)

Required heart monitoring

• Before starting: obtain an electrocardiogram to look for conduction problems.

• Contraindications include recent heart attack, stroke, or certain heart failure, and second‑degree type II or third‑degree AV block unless a pacemaker is present. Ozanimod also lists severe untreated sleep apnea and concurrent monoamine oxidase inhibitor use as contraindications. (drugs.com)

• First doses can cause a temporary drop in heart rate. Ozanimod requires a slow dose ramp over 7 days. For both drugs, seek cardiology input if the person uses class Ia or III antiarrhythmics or is on multiple heart rate–lowering drugs. Monitor blood pressure during therapy. (drugs.com)

Required eye monitoring

• S1P modulators can cause macular edema, a swelling in the center of the retina that can harm vision.

• Both labels recommend a baseline eye exam of the fundus, including the macula, near treatment start, periodic follow‑up while on therapy, and urgent evaluation for any vision changes. Risk is higher with diabetes or prior uveitis. (drugs.com)

Other safety and monitoring

• Infections: obtain a complete blood count, including lymphocytes, before starting. Monitor for infection during therapy and after stopping, for about 5 weeks with etrasimod and 3 months with ozanimod because effects on lymphocytes persist. Test varicella‑zoster immunity and vaccinate if needed before therapy. Avoid live vaccines during treatment and for the same post‑treatment windows. (dailymed.nlm.nih.gov)

• Liver: get baseline liver enzymes and repeat periodically. Stop if drug‑induced liver injury is suspected. (drugs.com)

• Lungs: both may cause small declines in lung function. Check spirometry if new or worsening shortness of breath appears. (drugs.com)

• Skin: skin exams are recommended at baseline and over time, with sun protection advice, since cutaneous cancers have been reported with this class. (drugs.com)

• Blood pressure: small average increases can occur, so periodic checks are advised. (dailymed.nlm.nih.gov)

Drug interactions to know

• Etrasimod and ozanimod both require caution with drugs that slow heart rate or prolong QT. Cardiology input is suggested if class Ia or class III antiarrhythmics are necessary. (dailymed.nlm.nih.gov)

• Ozanimod must not be combined with monoamine oxidase inhibitors. Rifampin can lower, and strong CYP2C8 inhibitors such as gemfibrozil can raise, ozanimod metabolite levels. (drugs.com)

• For both drugs, avoid combining with other potent immunosuppressants unless a specialist recommends and monitors it closely. (drugs.com)

Pregnancy and family planning

• Both medicines may harm a fetus. Effective contraception is required during therapy. Continue contraception for 3 months after stopping ozanimod and for 1 week after stopping etrasimod. Discuss pregnancy plans in advance to allow for washout. (drugs.com)

Ozanimod vs etrasimod: quick comparison

FAQs

Is first‑dose observation required

Routine in‑clinic first‑dose observation is not required by label for either drug. Ozanimod uses a 7‑day dose ramp to reduce heart‑rate effects, and both labels call for a baseline ECG and added caution if there are heart rhythm risks. (drugs.com)

How soon might symptoms improve

In trials, outcomes were assessed at week 10 for ozanimod and week 12 for etrasimod, with benefits maintained at one year for responders. Some people may notice improvements earlier. (pubmed.ncbi.nlm.nih.gov)

Can these be used with biologics or JAK inhibitors

They are generally not combined with other advanced immunosuppressive therapies because of additive immune effects. Switching is possible with proper timing and oversight. (drugs.com)

Are these options for Crohn’s disease

Not in the U.S. as of November 7, 2025. Research for ozanimod in Crohn’s did not meet key endpoints, and etrasimod is not approved for Crohn’s. (reuters.com)