What is the initial treatment for an ulcerative colitis (UC) flare?

Initial Treatment for Ulcerative Colitis Flare

The initial treatment for an ulcerative colitis flare should be a combination of topical mesalazine (≥1 g/day) plus oral mesalazine (≥2.4 g/day), which is more effective than either treatment alone for controlling inflammation and symptoms. 1, 2

Treatment Algorithm Based on Disease Severity

Mild to Moderate UC Flare

• Start with combination therapy of oral mesalazine 2-3 g/day plus topical mesalazine (enemas or suppositories) 3, 1
• For patients already on 5-ASA therapy who are flaring, escalate oral dose to 4-4.8 g/day alongside 5-ASA enemas 3, 2
• Once-daily dosing with mesalazine is as effective as divided doses and may improve adherence 1, 2
• The median time to cessation of rectal bleeding is approximately 9 days with high-dose mesalazine (4.8 g/day) compared to 16 days with standard dose (2.4 g/day) 1
• Continue treatment for up to 40 days before determining failure, as sustained complete remission may take time 1

When 5-ASA Therapy Fails

• If no response to optimized mesalazine therapy after 40 days, or symptoms worsen, add oral prednisolone 40 mg daily with tapering over 6-8 weeks 3
• Alternatively, consider budesonide MMX 9 mg/day for left-sided disease as it has fewer systemic side effects than conventional steroids 3, 1
• Single daily dosing of prednisolone is as effective as split-dosing and causes less adrenal suppression 3

Moderate to Severe UC Flare

• Oral prednisolone 40 mg daily weaning over 6-8 weeks is the recommended initial treatment 3
• There is no evidence of benefit with doses higher than 40-60 mg/day, and higher doses may increase adverse effects 3
• Approximately 50% of patients experience short-term corticosteroid-related adverse events such as acne, edema, sleep and mood disturbance, glucose intolerance and dyspepsia 3

Disease-Specific Considerations

Based on Disease Location

• For proctitis: Mesalazine 1-g suppository once daily is the preferred initial treatment 1
• For left-sided colitis: Aminosalicylate enema ≥1 g/day combined with oral mesalazine ≥2.4 g/day 1, 2
• For extensive colitis: Oral mesalazine 2-3 g/day plus topical therapy if tolerated 3, 1

Important Monitoring and Precautions

• 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 3, 1
• Always exclude infectious causes before attributing symptoms to IBD flare 2
• Long-term steroid use should be avoided due to significant side effects 3, 2

Escalation Therapy

• Patients who required two or more courses of corticosteroids in the past year, or who become corticosteroid-dependent or refractory, require treatment escalation with thiopurine, anti-TNF therapy, vedolizumab, or tofacitinib 3
• In clinical trials, mesalamine at 4.8 g/day showed superior efficacy compared to 2.4 g/day for active disease, with response rates between 40%-70% and remission rates of 15%-20% 4

Maintenance Therapy

• After achieving remission, maintenance therapy with mesalazine should be continued to prevent relapse 1, 2
• Lifelong maintenance therapy is generally recommended, especially for those with left-sided or extensive disease 1, 2

The evidence strongly supports starting with combination topical and oral mesalazine therapy for mild to moderate UC flares, with escalation to corticosteroids if necessary. This approach maximizes efficacy while minimizing potential adverse effects from steroids.