What are the treatment options for ulcerative colitis?

Treatment Options for Ulcerative Colitis

Treatment for ulcerative colitis 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, 2

Treatment Based on Disease Extent and Severity

Mild-to-Moderate Disease

• For patients with proctitis (disease limited to rectum):

  • First-line: Mesalamine 1-g suppository once daily is the preferred initial treatment 1, 2
  • Topical mesalamine is more effective than topical corticosteroids and should be preferred 2, 3
  • Suppositories deliver medication more effectively to the rectum and are better tolerated than enemas for proctitis 2

• For patients with left-sided colitis:

  • First-line: Combination of aminosalicylate enema ≥1 g/day with oral mesalazine ≥2.4 g/day 1, 2
  • This combination is more effective than either oral or topical aminosalicylates alone 2, 3
  • Once-daily dosing of oral mesalamine is as effective as divided doses and improves adherence 1, 2

• For patients with extensive disease:

  • First-line: Standard dose mesalamine (2-3 grams/day) or diazo-bonded 5-ASA 1
  • Adding rectal mesalamine to oral 5-ASA therapy is recommended for better outcomes 1, 3
  • For suboptimal response, increase to high-dose mesalamine (>3 grams/day) with rectal mesalamine 1

Treatment Escalation Algorithm

• If no improvement within 10-14 days or symptoms worsen on 5-ASA therapy:

  • Consider increasing oral mesalamine dose to 4.8 g/day 2
  • Continue optimized 5-ASA therapy for up to 40 days before determining failure 2
  • The median time to cessation of rectal bleeding is approximately 9 days with high-dose mesalamine (4.8 g/day) compared to 16 days with standard dose (2.4 g/day) 2

• If inadequate response to optimized mesalamine therapy:

  • Add oral corticosteroids such as prednisolone 40 mg daily with tapering over 6-8 weeks 1, 2
  • Alternatively, consider budesonide MMX 9 mg/day for left-sided disease as it has fewer systemic side effects 2

Moderate-to-Severe Disease

• Oral corticosteroid therapy (prednisolone 40 mg daily) is appropriate for induction of remission 1, 3
• After successful induction with corticosteroids, transition to maintenance therapy with 5-ASA, thiopurines, anti-TNF agents (with or without thiopurine/methotrexate), or vedolizumab 1
• For corticosteroid-resistant/dependent UC, anti-TNF therapy (such as infliximab) or vedolizumab is recommended 1, 4

Severe Disease

• Severe UC requires hospital admission and joint management by gastroenterologist and colorectal surgeon 1, 3
• Treatment includes:
  • Intravenous fluid and electrolyte replacement 1
  • Maintaining hemoglobin >10 g/dl 1
  • Subcutaneous heparin to reduce thromboembolism risk 1
  • Intravenous steroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) 1
  • For patients with acute severe UC refractory to IV corticosteroids, infliximab or cyclosporine may be considered 1, 4

Biologic Therapy

• Infliximab is FDA-approved for moderately to severely active ulcerative colitis in patients with inadequate response to conventional therapy 4, 5
• 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 4
• Other biologic options include vedolizumab (anti-α4β7 integrin) and ustekinumab (anti-IL-12/23) 6
• Small molecule therapies like tofacitinib (JAK inhibitor) and ozanimod (sphingosine-1-phosphate modulator) are also available for moderate-to-severe UC 6

Maintenance Therapy

• Lifelong maintenance therapy is generally recommended, especially for patients with left-sided or extensive disease 1, 2
• 5-ASA compounds are effective and safe for maintenance therapy 3
• Patients in remission with biologics and/or immunomodulators after prior failure of 5-ASA may discontinue 5-aminosalicylates 1
• Regular monitoring of renal function is recommended for patients on long-term 5-ASA therapy, including eGFR before starting, after 2-3 months, and then annually 2

Important Considerations and Cautions

• Long-term steroid use should be avoided due to significant side effects 2
• Approximately 50% of patients experience short-term corticosteroid-related adverse events such as acne, edema, sleep and mood disturbance, glucose intolerance, and dyspepsia 2
• Patients treated with biologics like infliximab should be screened for tuberculosis and other infections prior to starting therapy 4
• Lymphoma and other malignancies have been reported in patients treated with TNF blockers, including rare cases of hepatosplenic T-cell lymphoma, particularly in young males with Crohn's disease or ulcerative colitis who received concomitant azathioprine or 6-mercaptopurine 4
• Despite advances in medical therapies, response rates to advanced treatments range from 30% to 60% in clinical trials, and approximately 7% of patients undergo colectomy within 5 years of diagnosis 6