What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

The treatment of ulcerative colitis should be tailored based on disease extent (proctitis, left-sided, or extensive) and severity (mild, moderate, severe), with aminosalicylates (5-ASA) as first-line therapy for mild to moderate disease, combined with topical therapy for distal disease, and systemic corticosteroids for more severe disease or those who fail to respond to 5-ASA therapy. 1

Treatment Based on Disease Location

Ulcerative Proctitis

• A mesalamine 1-g suppository once daily is the preferred initial treatment for mild or moderately active proctitis 2, 1
• 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, 1
• 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 Ulcerative 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
• If symptoms deteriorate, rectal bleeding persists beyond 10–14 days, or sustained relief is not achieved after 40 days of appropriate 5-ASA therapy, additional therapy with oral systemic steroids should be started 2

Extensive Ulcerative 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, 1
• 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

Treatment Based on Disease Severity

Mild to Moderate Disease

• First-line therapy is 5-ASA compounds (mesalamine 2-4g daily) 2, 3
• High dose mesalamine (4 g/daily) may be sufficient initial therapy 2, 4
• Combining oral and topical 5-ASA is more effective than either alone 1
• Once-daily dosing with mesalamine is as effective as divided doses 2
• If no response to oral 5-ASA within 2-4 weeks, oral corticosteroids should be initiated 2, 1
• Budesonide MMX 9 mg/day can be considered for patients with left-sided disease who are inadequately controlled with oral 5-ASA before escalating to conventional steroids 2

Moderate to Severe Disease

• Oral prednisolone 40 mg daily is appropriate for patients with moderate to severe disease or those with mild to moderate disease that has failed to respond to oral mesalamine 2, 1
• Prednisolone should be reduced gradually according to severity and patient response, generally over 8 weeks 2
• Intravenous steroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) are appropriate for patients with severe disease 2
• 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 2

Severe Disease Requiring Hospitalization

• Joint medical and surgical management is appropriate 2
• Monitoring should include vital signs, stool chart, laboratory tests (CBC, ESR, CRP, electrolytes, albumin), and abdominal radiography if colonic dilatation is present 2
• Intravenous fluid and electrolyte replacement, blood transfusion to maintain hemoglobin >10 g/dl, and subcutaneous heparin to reduce thromboembolism risk 2
• Patients should be kept informed of treatment and prognosis, including a 25–30% chance of needing colectomy 2

Medication Options

5-Aminosalicylates (5-ASA)

• First-line therapy for mild to moderate UC 2, 3
• Options include mesalamine (2-4g daily), balsalazide (6.75g daily), olsalazine (1.5-3g daily) 1, 5
• ≥2 g/day oral 5-ASA induces remission more effectively than lower doses 2
• Patients with moderate disease may benefit from the higher dose of 4.8 g/day 2, 4
• Once-daily dosing is as effective as divided doses and may improve compliance 2
• 5-ASA has a favorable safety profile compared to immunomodulators and biologics 4, 5

Corticosteroids

• Indicated for moderate to severe UC or when 5-ASA therapy fails 1
• Oral prednisolone 40 mg daily is standard dosing 2, 1
• Budesonide MMX 9 mg/day can be used for left-sided disease in patients inadequately controlled with 5-ASA 2
• Prednisolone should be tapered gradually over 8 weeks 2
• Not recommended for long-term maintenance due to side effects 2, 1

Immunomodulators

• Azathioprine (1.5-2.5mg/kg/day) or mercaptopurine (0.75-1.5mg/kg/day) are indicated for steroid-dependent disease 1
• Can be used for maintenance therapy but usually require induction with another agent, often a corticosteroid 2
• Suggested alongside infliximab therapy 2

Biologics

• 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 ulcerative colitis who have had an inadequate response to conventional therapy 6
• The recommended dose of infliximab is 5 mg/kg given as an intravenous induction regimen at 0,2, and 6 weeks followed by a maintenance regimen of 5 mg/kg every 8 weeks 6
• Other biologics include monoclonal antibodies against α4β7 integrins (vedolizumab) and interleukin-12/23 (ustekinumab) 3

Small Molecules

• Janus kinase inhibitors (e.g., tofacitinib) and sphingosine-1-phosphate modulators (e.g., ozanimod) are newer options for moderate to severe UC 3

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
• Maintenance therapy should be continued with the agent successful in achieving induction, with the important exception that corticosteroids are not recommended for long-term maintenance 2
• 5-ASA compounds are effective and safe for maintenance therapy 1, 5
• Aminosalicylates may reduce the risk of colorectal cancer 2, 7

Treatment Considerations and Pitfalls

• Despite advances in medical therapies, the highest response to advanced treatments ranges from 30% to 60% in clinical trials 3
• Within 5 years of diagnosis, approximately 20% of patients with UC are hospitalized and approximately 7% undergo colectomy 3
• The risk of colorectal cancer after 20 years of disease duration is 4.5% 3
• Treatment goals have shifted from achieving clinical response to achieving biochemical, endoscopic, and histological remission 2, 8
• Patients with UC have a lower life expectancy (approximately 5 years shorter than people without UC) and require monitoring of symptoms, biomarkers of inflammation, and colonoscopy for dysplasia surveillance 3
• When initiating biologic therapy, screening for tuberculosis and other infections should be performed 6