What is the recommended treatment approach for a patient with ulcerative colitis?

Treatment Approach for Ulcerative Colitis

The treatment of ulcerative colitis must be stratified by disease severity and extent: mild-to-moderate disease requires 5-aminosalicylates as first-line therapy, while moderate-to-severe disease necessitates advanced therapies including biologics (infliximab, vedolizumab, ustekinumab) or JAK inhibitors, with infliximab and vedolizumab preferred as first-line biologics in biologic-naïve patients. 1, 2

Mild-to-Moderate Disease

Extensive Disease (Beyond Splenic Flexure)

• Initiate standard-dose oral mesalamine 2-3 grams/day as first-line therapy, which is superior to low-dose mesalamine or sulfasalazine 1, 2
• Add rectal mesalamine to oral therapy for superior outcomes, as combination therapy achieves better remission rates than monotherapy 1, 3
• Use once-daily dosing of oral mesalamine rather than multiple daily doses to improve adherence 1

Suboptimal Response to Standard Therapy

• Escalate to high-dose mesalamine (>3 grams/day) combined with rectal mesalamine for patients with inadequate response to standard dosing or those with moderate disease activity 1, 3
• If symptoms persist despite optimized 5-ASA therapy (after 40 days), initiate oral prednisolone 40 mg daily for induction of remission 1, 3
• Budesonide MMX can be considered as an alternative to systemic corticosteroids, though standard mesalamine is preferred initially 1

Distal Disease (Proctitis and Proctosigmoiditis)

• For proctitis: Use mesalamine 1-gram suppositories once daily as the preferred initial treatment, which delivers medication more effectively to the rectum 3
• For proctosigmoiditis: Use mesalamine enemas (≥1 gram/day) combined with oral mesalamine (≥2.4 grams/day), which is more effective than monotherapy 3
• Topical mesalamine is superior to topical corticosteroids for treating distal disease 3
• For patients intolerant of mesalamine suppositories or enemas, rectal corticosteroid foam preparations may be used 1

Moderate-to-Severe Disease

First-Line Advanced Therapy Selection

• Infliximab and vedolizumab are the preferred first-line biologics in biologic-naïve patients with moderate-to-severe UC 1, 2
• The AGA strongly recommends using infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, and guselkumab over no treatment 1
• Adalimumab, filgotinib, and mirikizumab are conditionally recommended alternatives 1

JAK Inhibitor Restrictions

• JAK inhibitors (tofacitinib, upadacitinib, filgotinib) should be reserved for patients with prior TNF antagonist failure or intolerance per FDA labeling 1
• In patients ≥65 years, current/long-term smokers, or those with cardiovascular disease or cancer history, use JAK inhibitors cautiously due to increased adverse cardiovascular risk 1

Combination Therapy Considerations

• Combine TNF antagonists with immunomodulators (thiopurines or methotrexate) rather than using TNF antagonist monotherapy, as combination therapy is more effective 1, 2
• For non-TNF biologics (vedolizumab, ustekinumab), there is insufficient evidence to recommend combination with immunomodulators over monotherapy 1

Corticosteroid-Dependent or Refractory Disease

• Transition to maintenance therapy with anti-TNF agents (with or without immunomodulators), vedolizumab, or other advanced therapies after successful corticosteroid induction 3, 2
• Thiopurine monotherapy is suggested against for inducing remission but may be used for maintaining remission induced with corticosteroids 1
• Methotrexate monotherapy is not recommended for inducing or maintaining remission 1

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Initial Management Protocol

• Joint management by gastroenterologist and colorectal surgeon is mandatory 3, 2, 4
• Initiate intravenous methylprednisolone 40-60 mg/day (or hydrocortisone 400 mg/day) as the mainstay of treatment 3, 2, 4
• Provide IV fluid and electrolyte replacement 3, 2, 4
• Maintain hemoglobin >10 g/dL with blood transfusion if needed 3, 2, 4
• Administer subcutaneous low-molecular-weight heparin for thromboprophylaxis 3, 2, 4
• Perform daily physical examination to assess for abdominal tenderness and rebound 3, 2

Assessment and Escalation

• Assess response by day 3 of IV corticosteroid therapy, as approximately 67% of patients respond to IV corticosteroids alone 4
• For patients refractory to IV corticosteroids, consider infliximab or cyclosporine as rescue therapy 1, 3, 4
• Early recognition of treatment failure is critical to allow timely introduction of rescue therapy or surgical intervention 4, 5

Maintenance Therapy

Long-Term Management Strategy

• Lifelong maintenance therapy is recommended for all patients, especially those with left-sided or extensive disease, to reduce relapse risk and potentially reduce colorectal cancer risk 3, 2, 4
• Maintenance options include aminosalicylates, thiopurines, and biologics depending on disease severity and prior response 3, 2, 4

De-escalation Considerations

• Patients in remission on biologics and/or immunomodulators after prior 5-ASA failure may discontinue 5-aminosalicylates 1, 3, 2
• Do not withdraw TNF antagonists in patients achieving corticosteroid-free remission for ≥6 months on combination therapy (TNF antagonist + immunomodulator) 1
• There is insufficient evidence to recommend for or against withdrawing immunomodulators while continuing biologic monotherapy 1

Critical Implementation Points

Biosimilars and Formulations

• Biosimilars of infliximab, adalimumab, and ustekinumab are equivalent to originator drugs in efficacy 1
• Subcutaneous formulations of infliximab and vedolizumab show comparable efficacy to intravenous maintenance doses 1

Extended Induction and Dose Optimization

• In patients with severe disease, extended induction regimens (up to 16 weeks) or dose escalation may be beneficial for certain agents 1
• For patients who initially respond to infliximab 5 mg/kg but subsequently lose response, consider escalation to 10 mg/kg 6
• Patients who do not respond by week 14 are unlikely to benefit from continued dosing and should be considered for alternative therapy 6

Monitoring and Safety

• Exclude infectious causes before initiating therapy, though treatment should not be delayed awaiting stool culture results in severe presentations 4
• Monitor disease activity using stool frequency, rectal bleeding, inflammatory markers (CRP, fecal calprotectin), and endoscopic assessment 4
• For patients on sulfasalazine, perform complete blood counts with differential and liver function tests every 2 weeks for the first 3 months, then monthly for the next 3 months, then every 3 months 7

Common Pitfalls to Avoid

• Do not use probiotics, curcumin, or fecal microbiota transplantation routinely, as there is insufficient evidence and their use risks delaying proven effective therapy 1, 3
• Do not continue ineffective therapy beyond appropriate trial periods—patients not responding to optimized 5-ASA after 40 days require escalation 1
• Do not use thiopurine or methotrexate monotherapy for inducing remission in active moderate-to-severe disease 1