What are the treatment options for ulcerative colitis?

Treatment of Ulcerative Colitis

Treatment for ulcerative colitis should be tailored based on disease location and severity, starting with 5-aminosalicylates (5-ASA) for mild-to-moderate disease, escalating to corticosteroids for inadequate response, and advancing to biologics or small molecules for moderate-to-severe or steroid-refractory disease. 1, 2

Treatment Algorithm by Disease Location and Severity

Ulcerative Proctitis (Disease Limited to Rectum)

• First-line therapy is mesalamine 1-g suppository once daily, which delivers medication most effectively to the rectum and is better tolerated than other formulations 2, 3
• Topical mesalamine is more effective than topical corticosteroids and should be preferred 2, 3
• Combining topical mesalamine with oral mesalamine (≥2.4 g/day) is more effective than either agent alone for patients requiring escalation 2, 3
• For refractory proctitis despite optimized 5-ASA therapy, consider oral corticosteroids, topical tacrolimus, JAK inhibitors, S1P agonists, or biologic therapy 1

Left-Sided Colitis (Disease to Splenic Flexure)

• Initial treatment should be aminosalicylate enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day, which is more effective than monotherapy 2, 3
• Mesalamine foam or liquid enemas are appropriate for disease extending beyond the rectosigmoid junction 2
• If no improvement within 10-14 days or symptoms worsen, escalate oral mesalamine to 4.8 g/day 3
• For patients not responding to optimized 5-ASA after 40 days, add oral prednisolone 40 mg daily with tapering over 6-8 weeks 1, 3

Extensive Colitis (Disease Beyond Splenic Flexure)

• Standard-dose mesalamine 2-4 g/day is first-line therapy for mild-to-moderate disease 1, 2
• Once-daily dosing is as effective as divided doses and improves adherence 2, 3
• Adding rectal mesalamine to oral therapy provides superior outcomes 2, 4
• For suboptimal response to standard-dose mesalamine, increase to high-dose (>3-4.8 g/day) with rectal mesalamine 2, 3

Corticosteroid Therapy

Indications and Dosing

• Prednisolone 40 mg daily is appropriate for moderate-to-severe disease or inadequate response to optimized 5-ASA within 2-4 weeks 1, 2
• Single daily dosing causes less adrenal suppression than split-dosing 3
• Taper gradually over 8 weeks according to severity and patient response; more rapid reduction is associated with early relapse 1
• Beclomethasone dipropionate or budesonide MMX 9 mg/day can be used as alternatives with fewer systemic side effects for left-sided disease 1, 3

Important Caveats

• Approximately 50% of patients experience short-term corticosteroid-related adverse events including acne, edema, sleep/mood disturbance, glucose intolerance, and dyspepsia 3
• Long-term corticosteroid use is undesirable and should be avoided 1, 3
• Patients requiring two or more courses of corticosteroids in the past year, or who become steroid-dependent or refractory, require treatment escalation 3

Advanced Therapy (Biologics and Small Molecules)

Indications for Escalation

• Advanced therapy should be started if there is no adequate response to oral corticosteroids within 2 weeks, if the corticosteroid taper is unsuccessful, or to avoid repeated courses of corticosteroids 1
• For corticosteroid-resistant or dependent disease, anti-TNF therapy (infliximab) or vedolizumab is recommended 2, 4
• Patients with chronic active steroid-dependent disease should be treated with azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day 1

Biologic Selection

• Infliximab and vedolizumab are preferred first-line biologics in biologic-naïve patients 4
• Infliximab (RENFLEXIS) is FDA-approved at 5 mg/kg IV at 0,2, and 6 weeks, then every 8 weeks for maintenance 5
• Combination therapy (biologic plus immunomodulator) is more effective than monotherapy 4
• JAK inhibitors (tofacitinib) and S1P modulators (ozanimod) are additional options for moderate-to-severe disease 1, 6

Acute Severe Ulcerative Colitis (Hospitalized Patients)

Management Approach

• Severe UC should be managed jointly by a gastroenterologist and colorectal surgeon 2, 4
• Daily physical examination is required to evaluate for abdominal tenderness and rebound 2, 4
• Intravenous corticosteroids are the mainstay: hydrocortisone 400 mg/day or methylprednisolone 40-60 mg/day 1, 2, 4

Supportive Care

• Provide IV fluid and electrolyte replacement 2, 4
• Maintain hemoglobin >10 g/dL 2, 4
• Administer subcutaneous heparin to reduce thromboembolism risk 2, 4
• Exclude infection before initiating treatment, though treatment need not wait for microbiological analysis 1

Refractory Disease

• For acute severe UC refractory to IV corticosteroids, infliximab or cyclosporine may be considered 2
• Ciclosporin may be effective for severe, steroid-refractory colitis 1
• Emergency surgery indications include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding 7

Maintenance Therapy

General Principles

• Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease 2, 3, 4
• After achieving remission, continue maintenance therapy with the agent successful in achieving induction, with the important exception that corticosteroids are not recommended for long-term maintenance 1
• Patients in remission with biologics and/or immunomodulators after prior failure of 5-ASA may discontinue 5-aminosalicylates 2, 4

Monitoring

• The overall treatment goal has shifted from achieving clinical response to achieving remission, assessed biochemically, endoscopically, and histologically 1
• Regular monitoring of renal function is recommended for patients on long-term 5-ASA therapy: eGFR before starting, after 2-3 months, then annually 3
• Monitor for response to therapy; adjust treatment if symptoms deteriorate, rectal bleeding persists beyond 10-14 days, or sustained relief has not been achieved after 40 days of appropriate 5-ASA therapy 2

Common Pitfalls to Avoid

• Do not use low-dose mesalamine (< 2 g/day) as initial therapy; start with standard doses of 2-4 g/day 2, 4
• Do not rely on oral therapy alone for distal disease; topical therapy is more effective and should be combined with oral agents 2, 3
• Do not continue corticosteroids beyond 8 weeks for maintenance; transition to steroid-sparing agents 1
• Do not delay surgical consultation in severe disease; close collaboration between gastroenterologist and surgeon is mandatory 7
• Sulfasalazine has a higher incidence of side effects compared with newer 5-ASA drugs and should be reserved for selected patients (e.g., those with reactive arthropathy) 1, 2