Biologics for ulcerative colitis: how they work and what to ask

Biologic medications represent a major advance in the treatment of moderate to severe ulcerative colitis. If you have heard the term from your gastroenterologist — or are wondering whether a biologic might be right for you — this guide explains what biologics are, how they differ from other UC medications, and what questions to ask before starting one.

What are biologics?

Biologics are a class of medications derived from living cells. Unlike traditional medications (which are chemically synthesized), biologics are large protein molecules that precisely target specific components of the immune system responsible for driving inflammation.

In UC, the immune system mistakenly attacks the lining of the colon. Biologics interrupt this process by blocking specific proteins or receptors involved in the inflammatory response. They are typically considered when aminosalicylates like mesalamine are not working well enough to control symptoms.

Types of biologics approved for UC

Several biologic medications are approved for ulcerative colitis in the United States. They differ in what target they block and how they are administered.

TNF-alpha inhibitors

These were the first biologics approved for UC. They block tumor necrosis factor-alpha (TNF-alpha), a protein that promotes inflammation.

Examples: Infliximab (Remicade), adalimumab (Humira), golimumab (Simponi)

• Infliximab is given by intravenous infusion at a clinic, typically every 8 weeks after initial loading doses
• Adalimumab is injected by the patient at home every 1–2 weeks
• Golimumab is injected monthly after initial doses

Biosimilar versions of infliximab and adalimumab (lower-cost alternatives to the original branded medications) are widely available.

Integrin inhibitors

These biologics prevent immune cells from entering the gut lining by blocking a protein called integrin. Vedolizumab (Entyvio) is gut-selective — it targets the gut specifically, rather than suppressing the immune system throughout the body. This may result in a more favorable safety profile.

Vedolizumab (Entyvio): Given by intravenous infusion or subcutaneous injection.

IL-12/23 inhibitors

Ustekinumab (Stelara) blocks interleukins 12 and 23, proteins involved in directing immune cell activity. Originally approved for Crohn’s disease and psoriasis, it is now also approved for UC.

Ustekinumab (Stelara): First dose is given by IV infusion; maintenance doses are injected every 8–12 weeks.

IL-23 inhibitors (newer)

Mirikizumab (Omvoh) and risankizumab (Skyrizi) are newer biologics that specifically target IL-23. They are approved for moderate to severe UC.

Who is a candidate for biologic treatment?

Biologics are typically considered for patients with:

• Moderate to severe UC symptoms
• Inadequate response to aminosalicylates (mesalamine/5-ASA)
• Dependence on corticosteroids to control symptoms
• Disease that has worsened despite standard maintenance therapy

Your gastroenterologist will assess your disease activity (typically via symptoms, blood tests, and sometimes endoscopy) before recommending a biologic. For a full comparison of how biologics fit into the treatment landscape, see our overview of ulcerative colitis treatment options.

What happens before starting a biologic?

Before starting most biologics, your doctor will:

• Test for latent tuberculosis (TB) — biologics can reactivate latent TB
• Screen for hepatitis B (some biologics)
• Review your vaccination history — certain vaccines (like live vaccines) cannot be given while on biologics; your doctor may recommend getting these before starting
• Review your current medications for interactions

What to expect after starting a biologic

Biologics do not always work immediately. Some patients see improvement within weeks; others take months to reach their full effect. Your gastroenterologist will typically reassess how you are responding after the initial treatment period (usually 10–14 weeks).

If one biologic does not work, switching to a different biologic — or to a different medication class such as JAK inhibitors — is a common next step.

Potential risks and side effects

Biologics are generally well-tolerated, but they do carry some risks:

• Increased infection risk: Because they modify immune activity, biologics can increase susceptibility to certain infections (respiratory infections, fungal infections, opportunistic infections in some cases)
• Infusion reactions: Some patients experience reactions during or shortly after IV infusions (chills, rash, low blood pressure)
• Injection site reactions: Redness or discomfort at the injection site
• Reduced effectiveness over time: Some patients develop antibodies against the biologic, reducing its effectiveness — this is called immunogenicity
• Reactivation of latent infections: Including TB, hepatitis B (for some biologics)

Your doctor will monitor you regularly with blood tests and clinical assessments.

Cost and access

Biologic medications can be expensive. However:

• Most manufacturers offer copay assistance programs for commercially insured patients that significantly reduce out-of-pocket costs
• Patient assistance programs exist for uninsured or underinsured patients
• Biosimilar versions of infliximab and adalimumab are available at lower cost

Ask your gastroenterologist’s office about which programs you may qualify for.

When to contact a doctor

Contact your healthcare provider if, while on a biologic, you experience:

• Signs of infection: fever, chills, persistent cough, unusual fatigue
• Skin reactions or rashes
• Symptoms of an infusion or injection reaction
• Your UC symptoms returning or worsening despite treatment
• Any new or unusual health changes

Questions to ask your doctor

• Is my disease severe enough to consider a biologic?
• Which biologic do you recommend and why?
• How is it administered — injection or infusion?
• What testing do I need before starting?
• How will we know if it is working?
• What should I do if I think I am getting an infection?
• Are there biosimilars or patient assistance programs available for cost?
• Can I get vaccines before starting?
• If this biologic stops working, what are my next options?

This content is for educational purposes only. It is not medical advice. Speak with your gastroenterologist before making any treatment decisions.