What are the recommended medication regimens for ulcerative colitis according to disease extent and severity?

Medications for Ulcerative Colitis

Treatment Strategy by Disease Severity

For moderate-to-severe ulcerative colitis, the AGA strongly recommends infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab as first-line advanced therapies, with infliximab and vedolizumab preferred in biologic-naïve patients based on network meta-analysis. 1

Mild Ulcerative Colitis

Initial Treatment:

• Aminosalicylates are first-line therapy: mesalazine 2-4 g/day or balsalazide 6.75 g/day 2
• For distal disease (proctitis to sigmoid-descending junction), combined topical mesalazine 1 g daily PLUS oral mesalazine 2-4 g daily is superior to either alone 2
• For extensive or left-sided disease, mesalazine 2-4 g daily, olsalazine 1.5-3 g daily, or balsalazide 6.75 g daily are equivalent options 2

Escalation if Inadequate Response:

• Prednisolone 40 mg daily for patients requiring rapid response or those failing aminosalicylates 2
• Taper prednisolone gradually over 8 weeks according to disease severity and response 2

Maintenance:

• Lifelong aminosalicylate maintenance therapy is recommended for all patients 2
• For steroid-dependent disease, add azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day 2

Moderate-to-Severe Ulcerative Colitis

Advanced Therapy Selection:

The 2024 AGA guideline provides the most current evidence-based hierarchy 1:

Strong recommendations (high-quality evidence):

• Infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab 1

Conditional recommendations (moderate-quality evidence):

• Adalimumab, filgotinib, or mirikizumab 1

First-Line Agent Selection:

• In biologic-naïve patients, infliximab or vedolizumab are preferred based on network meta-analysis over standard-dose adalimumab or golimumab 1
• In patients with prior infliximab exposure, particularly primary non-response, vedolizumab or tofacitinib are preferred over adalimumab or golimumab 1

Critical FDA Restriction:

• JAK inhibitors (tofacitinib, filgotinib, upadacitinib) are restricted to patients with prior failure or intolerance to TNF antagonists in the United States 1
• European Medicine Agency recommends cautious use as first-line in patients ≥65 years, current/previous long-term smokers, history of cardiovascular disease, or history of cancer 1

Combination Therapy vs. Monotherapy

TNF Antagonists:

• Combine TNF antagonists with immunomodulators (thiopurines) rather than monotherapy—this is more effective than either agent alone 1

Non-TNF Biologics:

• No recommendation exists for combining non-TNF biologics with immunomodulators over monotherapy due to knowledge gap 1

Immunomodulator Monotherapy:

• Do NOT use thiopurine monotherapy for inducing remission in active disease 1
• May use thiopurine monotherapy for maintaining remission typically induced with corticosteroids (conditional recommendation) 1
• Do NOT use methotrexate monotherapy for induction or maintenance of remission 1

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Initial Management:

• Intravenous methylprednisolone 40-60 mg/day (or equivalent) is mainstay therapy 1, 3
• Continue for 3-5 days with assessment of response 3
• Do NOT extend beyond 7 days if patient is not responding 3
• Doses above 60 mg daily provide no additional benefit 3

Assessment at 3-5 Days:

• Monitor stool frequency, blood in stool, fever, heart rate, CRP, and albumin 3
• If inadequate response after 3-5 days, initiate salvage therapy rather than prolonging steroids 3

Salvage Therapy:

• Either infliximab or cyclosporine for corticosteroid-refractory disease 1
• No recommendation can be made regarding intensive vs. standard infliximab dosing in this setting due to lack of robust evidence 1

Transition:

• Once clinical response achieved, transition to oral prednisolone 40 mg daily 3
• Taper gradually over 8 weeks—more rapid reduction increases relapse risk 3

De-escalation Strategies

5-Aminosalicylate Discontinuation:

• In patients who failed 5-ASA and escalated to immunomodulators or advanced therapies, STOP 5-aminosalicylates 1

Combination Therapy De-escalation:

• In patients in corticosteroid-free remission for ≥6 months on TNF antagonist + immunomodulator combination, do NOT withdraw the TNF antagonist 1
• No recommendation exists regarding withdrawing immunomodulators or continuing combination therapy (knowledge gap) 1

Important Implementation Considerations

Biosimilars:

• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs in efficacy 1

Subcutaneous Formulations:

• Subcutaneous infliximab and vedolizumab show comparable efficacy to intravenous maintenance doses 1

Extended Induction:

• In severe disease, extended induction regimens (up to 16 weeks) or dose escalation may be beneficial for certain agents 1

Disease Extent Considerations:

• Recent patient-level analysis suggests tofacitinib may have greater efficacy in extensive colitis compared to left-sided disease for clinical remission and symptom reduction 4
• Infliximab showed greater clinical remission rates in extensive colitis during induction 4

Common Pitfalls to Avoid

• Do not use thiopurine or methotrexate monotherapy for induction of remission in active moderate-to-severe disease 1
• Do not continue intravenous corticosteroids beyond 7-10 days in non-responding hospitalized patients 1, 3
• Do not use JAK inhibitors as first-line in the United States without prior TNF antagonist failure 1
• Do not continue 5-ASA after escalating to advanced therapies in patients who failed 5-ASA 1
• Do not withdraw TNF antagonists in patients stable on combination therapy, even if considering de-escalation 1