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

Initial Treatment for Ulcerative Colitis Flare

For a UC flare, start combination therapy with oral mesalazine ≥2.4 g/day plus topical mesalazine (1 g suppository for proctitis or 1 g enema for left-sided disease) administered once daily, which is more effective than either treatment alone for controlling inflammation and achieving remission. 1, 2

Treatment Algorithm Based on Disease Location

Proctitis (Rectal Disease Only)

• First-line: Mesalazine 1 g suppository once daily 1
• Suppositories deliver medication more effectively to the rectum than foam or enemas and are better tolerated 1
• Add oral mesalazine ≥2.4 g/day to the suppository for enhanced efficacy 3, 1

Left-Sided Colitis

• First-line: Mesalazine enema ≥1 g/day combined with oral mesalazine ≥2.4 g/day 1, 2
• This combination is superior to either oral or topical aminosalicylates alone 1
• Once-daily dosing is as effective as divided doses and improves adherence 3, 1

Extensive Colitis

• First-line: Oral mesalazine 2.4-3 g/day plus topical mesalazine (enemas) 1, 2
• For patients already on 5-ASA who are flaring, escalate oral dose to 4-4.8 g/day alongside topical therapy 1

Treatment Escalation Strategy

If No Improvement After 10-14 Days

• Increase oral mesalazine to 4.8 g/day while continuing topical therapy 1
• 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

If Inadequate Response After 40 Days or Symptoms Worsen

• Add oral prednisolone 40 mg once daily with tapering over 6-8 weeks 3, 1, 2
• Single daily dosing causes less adrenal suppression than split-dosing 1
• Alternative: Budesonide MMX 9 mg/day for left-sided disease (fewer systemic side effects than conventional steroids) 1, 2

Severe Flare Requiring Hospitalization

• Intravenous corticosteroids as first-line treatment 3, 4
• If no response after 3-5 days, initiate rescue therapy with either:
  • Infliximab: 5 mg/kg at weeks 0,2, and 6 3
  • Ciclosporin: 2 mg/kg/day continuous IV infusion, then convert to oral 4 mg/kg/daily for 3 months (target trough 150-250 ng/mL) 3
• Joint management by gastroenterology and colorectal surgery is essential 2

Critical Considerations

Before Starting Treatment

• Always exclude infectious causes (C. difficile, CMV, bacterial pathogens) before attributing symptoms to UC flare 2
• Check baseline renal function (eGFR) before starting 5-ASA therapy 1

Monitoring During Treatment

• Recheck renal function after 2-3 months, then annually for patients on long-term 5-ASA 1
• Monitor clinical response using Mayo score or partial Mayo score 3
• Consider biomarkers (fecal calprotectin >150 mg/g, elevated CRP) to confirm active inflammation in symptomatic patients 3

Common Pitfalls to Avoid

• Do not use topical corticosteroids as first-line therapy - topical mesalazine is more effective 1, 2
• Avoid long-term steroid use due to significant side effects; approximately 50% of patients experience short-term corticosteroid-related adverse events 1
• Do not delay treatment escalation - patients requiring two or more courses of corticosteroids in the past year need escalation to thiopurines, anti-TNF therapy, vedolizumab, or tofacitinib 1
• Do not use mesalazine monotherapy without topical therapy for distal disease - combination is significantly more effective 3, 1, 2

Dosing Evidence

• Doses ≥2 g/day are more effective than <2 g/day for achieving remission (RR 0.91; 95% CI 0.85 to 0.98) 3
• Patients with moderate disease respond better to 4.8 g/day, while those with mild disease show no significant dose-response difference 3
• Some patients who do not respond to 8 weeks of standard-dose 5-ASA may achieve remission after a further 8 weeks of high-dose (4.8 g) therapy 1