Ulcerative Colitis: Science, Choice, and Hope

 This article is based on the most recent clinical guidelines from the American Gastroenterological Association (AGA), published in the journal Gastroenterology in 2020: “AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis” (Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S, on behalf of the AGA Institute Clinical Guidelines Committee). The team behind this document includes leading gastroenterologists, clinical researchers, and academic professors from top U.S. medical centers specializing in the treatment and study of inflammatory bowel disease (IBD). Their guidelines are the result of a thorough analysis of the latest scientific data and clinical trials, providing patients and their loved ones with the most reliable and evidence-based information available. The following sections present key questions and answers that every patient with moderate to severe ulcerative colitis should understand — to be better informed and to work effectively with their care team.

“Modern treatment of ulcerative colitis requires informed decision-making, a personalized approach, and a partnership between the patient and the healthcare team.”

Expert Opinions

Moderate to severe ulcerative colitis (UC) is a serious chronic inflammatory bowel disease that impacts quality of life, requires long-term treatment, and often involves difficult medical decisions for patients, caregivers, and doctors alike. To navigate the most effective, science-based approaches, it is essential for those affected to have access to up-to-date and unbiased expert recommendations. Below is a summary of expert insights from the latest AGA clinical guidelines — helpful for both patients and their families.

1. What are the most effective medications for moderate to severe ulcerative colitis? 

For outpatient adults with moderate to severe ulcerative colitis, the AGA recommends using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment.

Interpretation: These are the main categories of medications proven to reduce disease activity and help manage symptoms as well as maintain remission. All of them are more effective than doing nothing and can be used both to induce and maintain remission. The choice depends on individual patient characteristics, contraindications, and preferences.

2. Which medication should I choose if I haven’t received biologic treatment before? 

For outpatients with moderate to severe UC who are naïve to biologic therapy, the AGA suggests using infliximab or vedolizumab rather than adalimumab for induction of remission.

Interpretation: If you’re new to biologic therapy, infliximab or vedolizumab are recommended first-line options, especially if your priority is effectiveness. However, if convenience is important to you (e.g., at-home injections), adalimumab may also be a reasonable choice, though some studies show it is slightly less effective.

3. What should I do if I no longer respond to initial treatment with infliximab? 

For outpatients with moderate to severe UC who have previously been treated with infliximab (especially those who were primary non-responders), the AGA suggests using ustekinumab or tofacitinib rather than vedolizumab or adalimumab for induction of remission.

Interpretation: If infliximab no longer works for you, the next step is to consider switching to a different class of medications — ustekinumab or tofacitinib. These drugs have different mechanisms of action and may be more effective in people who did not respond to their initial therapy.

4. What is the role of immunosuppressants like thiopurines and methotrexate? 

The AGA suggests against using thiopurine monotherapy for induction of remission... and does not recommend methotrexate monotherapy for induction or maintenance of remission in moderate to severe UC.

Interpretation: Monotherapy with immunosuppressants like azathioprine and methotrexate isn’t effective enough for active disease, though thiopurines may be used to maintain remission once achieved with other treatments (such as corticosteroids). Methotrexate is not recommended for UC at all.

5. How is acute severe ulcerative colitis treated in hospitalized patients? 

The AGA suggests using intravenous methylprednisolone at 40–60 mg/day instead of higher doses of corticosteroids to treat acute severe UC in a hospital setting... For patients who do not respond to corticosteroids, infliximab or cyclosporine is recommended.

Interpretation: The main treatment for severe UC flares requiring hospitalization is corticosteroids. If there’s no improvement after 3–5 days, infliximab or cyclosporine is recommended as the next step, with the goal of avoiding surgery (colectomy).

Questions and Answers

1. How is it determined whether my UC is moderate, severe, or acute severe (ASUC)? 

Answer: The classification is based on the number of bloody bowel movements per day, presence of systemic signs (fever, heart rate, hemoglobin levels, and elevated ESR), and endoscopic findings (such as ulcers). For example, severe UC typically means more than six bloody stools per day plus at least one systemic sign (like fever over 100°F, heart rate over 90 bpm, hemoglobin <10.5 g/dL, ESR >30 mm/h). Acute severe UC (ASUC) requires hospitalization and carries a high risk of complications, including potential need for surgery.

2. What are the risks of needing surgery (colectomy), and what increases those risks? 

Answer: Among patients with moderate to severe UC, 10–15% may require surgery within 5–10 years. Those at higher risk include younger individuals (under age 40), people with extensive colon involvement, those with large or deep ulcers seen on endoscopy, extraintestinal symptoms, early need for corticosteroids, or high levels of inflammatory markers. For hospitalized patients with ASUC, 25–30% may need surgery in the short term.

3. When should biologic therapies be used, and when are they not recommended? 

Answer: The guidelines recommend earlier use of biologic agents (or tofacitinib) in patients with more severe disease or high risk of surgery, rather than waiting for traditional medications (like 5-ASA) to fail. For patients with milder disease concerned about side effects, a more stepwise approach may be discussed. Biologic drugs are generally not used for mild UC and should not be combined with 5-ASA if remission has already been achieved with other treatments.

4. Is there any benefit to continuing 5-ASA medications after starting biologic or immunosuppressive therapy? 

Answer: If you’ve reached the point of needing biologic or immunosuppressive treatment (e.g., thiopurines or tofacitinib), continuing 5-ASA is not recommended for inducing or maintaining remission, as there’s no proven added benefit. This is especially true if 5-ASA has already failed. Evidence does not support combining these drugs at this stage of the disease.

5. When and how are corticosteroids used during severe flare-ups, and why aren’t antibiotics routinely given? 

Answer: In a hospital setting, during a severe flare (ASUC), the standard is IV methylprednisolone at 40–60 mg/day. Higher doses don’t offer more benefit and may increase side effects. If there’s no improvement in 3–5 days, switching to infliximab or cyclosporine is the next step. Routine use of antibiotics is not recommended unless there is a confirmed infection, as studies show no benefit in reducing surgery risk or improving clinical outcomes during purely inflammatory flares.

Conclusion

Modern treatment of moderate to severe ulcerative colitis requires a precise and individualized approach grounded in the latest scientific evidence and strong collaboration between the patient and healthcare providers. The clinical guidelines from the American Gastroenterological Association provide scientifically validated, practical information that helps patients make informed decisions about their care — from recognizing disease severity and choosing the most appropriate therapies, to knowing what to do during severe flare-ups. Reliable communication between patients and medical teams — guided by transparent recommendations and personal preferences — is the best path toward successful disease management and a better quality of life.

Source: Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S, on behalf of the AGA Institute Clinical Guidelines Committee. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology 2020;158:1450–1461. DOI: 10.1053/j.gastro.2020.01.006