JAK Inhibitors (Tofacitinib, Upadacitinib) and S1P Modulators
Oral medications for ulcerative colitis and Crohn's — fast-acting alternatives to injectable biologics. Convenient pill form, but higher cardiovascular and infection risk than some biologics.
This article is educational and does not replace your doctor's advice. Seek urgent care for any red-flag symptoms.
Drug class
JAK inhibitors (Janus Kinase inhibitors) and S1P (sphingosine-1-phosphate) modulators
Examples
JAK inhibitors: tofacitinib (Xeljanz), upadacitinib (Rinvoq), filgotinib (Jyseleca). S1P modulator: ozanimod (Zeposia), etrasimod (Velsipity).
How it works
JAK inhibitors block intracellular signals that activate inflammation — many cytokines route through JAK enzymes. S1P modulators keep certain inflammatory white blood cells trapped in lymph nodes, preventing them from reaching the gut.
What it treats
- Moderate-to-severe ulcerative colitis (tofacitinib, upadacitinib, ozanimod, etrasimod)
- Moderate-to-severe Crohn's disease (upadacitinib)
- Other autoimmune diseases (rheumatoid arthritis, psoriatic arthritis)
How to take it
Tofacitinib 10 mg twice daily (induction), then 5 mg twice daily (maintenance).
Upadacitinib 45 mg daily for 8-12 weeks (induction), then 15-30 mg daily (maintenance).
Ozanimod dose-titration over the first week, then 0.92 mg daily.
All oral; can be taken with or without food.
Common side effects
- Increased risk of upper respiratory infections, herpes simplex/zoster
- Headache, nausea
- Cholesterol may rise (manageable with statins)
- Nasopharyngitis
Serious side effects — call your doctor
Heart attack, stroke, or blood clot symptoms
JAK inhibitors carry cardiovascular and thrombosis risk — emergency assessment.
Severe infection (bacterial, viral, fungal)
Hold medication; treat infection.
Shingles (painful rash)
Significantly increased risk; antiviral treatment needed.
New skin lesions, lumps, or persistent infection
Investigate for malignancy.
Slow heart rate or fainting at start of S1P modulator
First-dose monitoring required for ozanimod.
Interactions
JAK inhibitors: avoid combining with other immunosuppressants. Some interact with strong CYP3A4 inhibitors. Don't give live vaccines.
S1P modulators: avoid with antiarrhythmics, beta-blockers (heart rate), MAO inhibitors. Need ECG before first dose.
Monitoring
Before starting: TB screening, hepatitis B/C, varicella immunity (consider vaccine), CBC, liver function, lipid panel, ECG (S1P).
During: CBC, liver function, lipids — every 3 months initially, then less often. Skin checks. Annual cancer screening.
When and how to stop
JAK inhibitors: in case of major adverse cardiovascular event, malignancy, severe infection. Don't stop without doctor — relapse common.
Pregnancy & breastfeeding
JAK inhibitors and S1P modulators are NOT recommended in pregnancy. Switch to a biologic before planning pregnancy. Effective contraception is required while on these drugs.
In the Saudi context
Available at major Saudi tertiary centers. Insurance coverage variable — usually requires prior authorization and biologic failure.
Questions to ask your doctor
Save this list or print it before your appointment — doctors appreciate prepared patients.
- Am I at higher cardiovascular risk if I take a JAK inhibitor?
- Do I need varicella vaccine before starting?
- Should I plan pregnancy first?
Medically reviewed by: SGA Patient Education Panel · Last reviewed 24/04/2026