What are the treatment options for managing ulcerative colitis?

Management of Ulcerative Colitis

The treatment of ulcerative colitis (UC) should be tailored based on disease extent, severity, and location, with 5-aminosalicylates (5-ASA) as first-line therapy for mild-to-moderate disease and escalation to corticosteroids, immunomodulators, or biologics for moderate-to-severe disease or those who fail initial therapy. 1

Treatment Based on Disease Location and Severity

Proctitis (Distal Disease)

• A mesalamine 1-g suppository once daily is the preferred initial treatment for mild or moderately active proctitis 2
• Mesalamine foam or enemas are an alternative, but suppositories deliver the drug more effectively to the rectum and are better tolerated 2
• Topical mesalamine is more effective than topical steroids 2
• Combining topical mesalamine with oral mesalamine or topical steroids is more effective than monotherapy 2
• Refractory proctitis may require treatment with systemic steroids, immunosuppressants, and/or biologics 2

Left-Sided Colitis

• Mild to moderately active left-sided UC should initially be treated with an aminosalicylate enema ≥1 g/day combined with oral mesalamine ≥2.4 g/day 2
• This combination is more effective than oral or topical aminosalicylates, or topical steroids alone 2
• Once-daily dosing with mesalamine is as effective as divided doses 2
• For patients who don't respond to 5-ASA, oral corticosteroids (prednisolone 40 mg daily) are appropriate 2
• Budesonide MMX 9 mg/day may be an alternative therapy for patients inadequately controlled with oral 5-ASA before escalating to conventional steroids 2

Extensive Colitis

• Mild to moderately active extensive UC should initially be treated with an aminosalicylate enema 1 g/day combined with oral mesalamine ≥2.4 g/day 2
• Systemic corticosteroids are appropriate in patients with moderate to severe activity and in those with mild activity who do not respond to mesalamine 2
• Severe extensive colitis is an indication for hospital admission for intensive treatment 2

Dosing and Formulations

• Standard dose mesalamine (2-3 grams/day) or diazo-bonded 5-ASA is recommended as first-line therapy for extensive disease 1
• High-dose mesalamine (>3 grams/day) with rectal mesalamine is suggested for suboptimal response to standard-dose or moderate disease activity 1
• Once-daily dosing of oral mesalamine is preferred over multiple daily dosing for better adherence 1
• There is no difference in efficacy between the various 5-ASA formulations 2

Management of Moderate-to-Severe UC

• Oral corticosteroids (prednisolone 40 mg daily) are appropriate for induction of remission 1
• After successful induction with corticosteroids, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents, or vedolizumab is recommended 1
• For corticosteroid-resistant/dependent UC, anti-TNF therapy (such as infliximab) or vedolizumab is recommended 1
• Infliximab is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active UC who have had an inadequate response to conventional therapy 3

Management of Severe UC

• Severe UC should be managed jointly by a gastroenterologist and colorectal surgeon 2
• Patients should receive intravenous fluid and electrolyte replacement, maintain hemoglobin >10 g/dl, with subcutaneous heparin to reduce thromboembolism risk 2
• Intravenous steroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) are appropriate for patients with severe disease 2
• For patients refractory to IV corticosteroids who prefer ongoing medical management, either infliximab or cyclosporine may be used 2

Maintenance Therapy

• Lifelong maintenance therapy is generally recommended for all patients, especially those with left-sided or extensive disease, and those with distal disease who relapse more than once a year 2
• Patients in remission with biologics and/or immunomodulators after prior failure of 5-ASA may discontinue 5-aminosalicylates 2

Special Considerations

• Patients should be monitored for response to therapy, with adjustment of treatment if symptoms deteriorate, rectal bleeding persists beyond 10-14 days, or sustained relief from all symptoms has not been achieved after 40 days of appropriate 5-ASA therapy 2
• There is some evidence for therapeutic benefit of probiotics (particularly VSL#3) when added to standard therapy to induce remission, but results are inconsistent 2
• Fecal transplantation has shown promising results in inducing remission in active UC in some trials, but additional studies are needed to define optimal protocols 2

Pitfalls and Caveats

• Patients with severe UC should be kept informed of treatment and prognosis, including a 25-30% chance of needing colectomy 2
• Patients treated with infliximab should be monitored for infections, particularly tuberculosis and invasive fungal infections 3
• Lymphoma and other malignancies have been reported in patients treated with TNF blockers, including infliximab 3
• The threshold for introducing oral steroids depends upon the response to and tolerance of 5-ASA, patient's preference, and physician's practice 2