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

Treatment of Choice for Ulcerative Colitis Flare

The treatment of choice for ulcerative colitis flare depends on disease extent, severity, and pattern, with 5-aminosalicylic acid (5-ASA) compounds as first-line therapy for mild to moderate disease, corticosteroids for moderate to severe disease, and biologics or calcineurin inhibitors for severe or refractory cases. 1

Assessment of Disease Severity and Extent

Disease severity should be categorized using validated criteria:

• Severe UC: Bloody stool frequency ≥6/day plus at least one of: tachycardia (>90/min), temperature >37.8°C, anemia (Hb <10.5 g/dl), or elevated ESR (>30 mm/h) or CRP (>30 mg/l) 1
• Moderate UC: Between mild and severe
• Mild UC: <4 stools/day with minimal blood, no systemic symptoms

Disease extent classification:

• Proctitis (rectum only)
• Left-sided colitis (up to splenic flexure)
• Extensive colitis (beyond splenic flexure)

Treatment Algorithm by Disease Severity and Extent

1. Mild to Moderate Proctitis

• First-line: Mesalamine 1g suppository once daily 1
  • Alternative: Mesalamine foam or enemas
  • Topical mesalamine is more effective than topical steroids
• For refractory cases: Consider combining topical mesalamine with oral mesalamine or topical steroids 1

2. Mild to Moderate Left-Sided or Extensive Colitis

• First-line: Oral 5-ASA (mesalamine) at doses of 2g or more daily 1
  • Once daily dosing is as effective as divided doses and may improve adherence
  • For left-sided disease, combine with topical 5-ASA for better efficacy
• For inadequate response after 2 weeks: Consider adding oral corticosteroids (prednisolone 40 mg/day) 1

3. Moderate to Severe UC (Outpatient Management)

• First-line: Oral corticosteroids (prednisolone 40 mg daily, tapered over 6-8 weeks) 1
• For steroid-dependent or steroid-refractory disease:
  • Consider thiopurines (azathioprine/6-mercaptopurine) for maintenance 1
  • Consider biologic therapy (infliximab, other TNF inhibitors, vedolizumab, or upadacitinib) 1, 2
  • Recent evidence suggests upadacitinib may be the most effective therapy for moderate-to-severe UC in both biologic-naïve and biologic-exposed populations 1

4. Severe UC Requiring Hospitalization (Acute Severe UC)

• First-line: Intravenous corticosteroids (methylprednisolone 60 mg/day or hydrocortisone 100 mg four times daily) 1
• If no response after 3-5 days: Rescue therapy with either:
  • Infliximab (5 mg/kg IV at 0,2, and 6 weeks, then every 8 weeks) 2
  • Ciclosporin (2 mg/kg/day IV) 1
• If no response to rescue therapy after 4-7 days: Emergency colectomy 3

Monitoring Response to Treatment

• For outpatient management: Assess clinical response within 2 weeks of initiating therapy 1
• For inpatient management: Daily assessment of vital signs, stool frequency, abdominal examination, and CRP 1
• Consider fecal calprotectin (>150 mg/g) to confirm active inflammation in patients with moderate to severe symptoms 1

Important Considerations and Pitfalls

• Avoid prolonged steroid therapy: Prolonging high-dose oral corticosteroids has diminishing returns and increases risk of complications 1
• Thromboprophylaxis: All hospitalized UC patients should receive subcutaneous low-molecular-weight heparin 1
• Exclude infections: Always test for Clostridioides difficile and cytomegalovirus in severe or refractory cases 1
• Don't delay surgery: Prolonged ineffective medical therapy in severe UC increases surgical complications and mortality 1
• Maintenance therapy: After achieving remission, appropriate maintenance therapy (5-ASA, thiopurines, or biologics) should be initiated to prevent relapse 1

By following this algorithmic approach based on disease severity and extent, clinicians can optimize outcomes for patients experiencing ulcerative colitis flares.