What is the best treatment approach for an ulcerative colitis flare?

Treatment of Ulcerative Colitis Flare

For a mild to moderate UC flare, start with combination therapy of oral mesalazine 2-3 g/day plus topical mesalazine 1 g/day (enemas or suppositories), and if already on 5-ASA therapy, escalate to 4-4.8 g/day orally alongside 5-ASA enemas. 1, 2

Initial Treatment Strategy

Mild to Moderate Flare

The cornerstone of treatment is combination therapy, which is more effective than either oral or topical therapy alone. 2

• Start with oral mesalazine 2-3 g/day combined with topical mesalazine ≥1 g/day 1, 2
• For proctitis specifically, use mesalazine 1-g suppository once daily as it delivers drug more effectively to the rectum than enemas 2
• For left-sided colitis, use aminosalicylate enema ≥1 g/day combined with oral mesalazine ≥2.4 g/day 2
• Once-daily dosing is as effective as divided doses and improves adherence 2

Treatment Escalation Timeline

If patients are already on 5-ASA therapy when they flare, immediately escalate the dose rather than continuing the same regimen. 1, 2

• Increase oral mesalazine to 4-4.8 g/day alongside 5-ASA enemas 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) 2
• Continue optimized mesalazine therapy for up to 40 days before determining treatment failure, as sustained remission may take time 2
• Some patients who don't respond to 8 weeks of standard-dose 5-ASA may achieve remission after a further 8 weeks of high-dose (4.8 g) therapy 2

When to Add Corticosteroids

If there is no improvement within 10-14 days on optimized mesalazine therapy, or if symptoms worsen, add oral corticosteroids. 1, 2

Moderate to Severe Flare

• Oral prednisolone 40 mg daily with tapering over 6-8 weeks is the standard approach 1, 2
• Single daily dosing of prednisolone is as effective as split-dosing and causes less adrenal suppression 2
• Prednisolone is superior to 5-ASA for induction of remission but has significant side effects, so reserve it for patients who fail or are intolerant to 5-ASA 1
• Approximately 50% of patients experience short-term corticosteroid-related adverse events including acne, edema, sleep and mood disturbance, glucose intolerance, and dyspepsia 1, 2

Alternative Corticosteroid Option

For patients wishing to avoid systemic corticosteroid side effects, particularly those with left-sided disease, consider budesonide MMX 9 mg/day. 1, 2

• Budesonide MMX 9 mg daily is significantly more effective than placebo and as effective as 5-ASA for mild to moderate UC 1
• Week 8 combined clinical and endoscopic remission rates were 17.7% for budesonide MMX 9 mg versus 6.2% for placebo 1
• Benefit is most significant for left-sided disease 1
• This option has fewer systemic side effects than conventional steroids 2

Advanced Therapy Indications

Patients requiring two or more courses of corticosteroids in the past year, or who become corticosteroid-dependent or refractory, require treatment escalation to advanced therapies. 1

• Options include thiopurine, anti-TNF therapy (infliximab), vedolizumab, or tofacitinib 1
• For moderate to severe UC with inadequate response to conventional therapy, infliximab 5 mg/kg IV at 0,2, and 6 weeks followed by maintenance every 8 weeks is indicated 3
• Long-term steroid use should be avoided due to significant side effects 2

Acute Severe UC (Hospitalization Required)

Approximately 20% of UC patients experience a severe flare requiring hospitalization during their disease course. 4

Inpatient Management Protocol

• Intravenous corticosteroids are first-line treatment for acute severe UC 4, 5
• Provide IV fluid and electrolyte replacement 6
• Start subcutaneous heparin for thromboprophylaxis 6, 4
• Provide nutritional support if needed 6, 4
• Close monitoring with regular laboratory assessments (C-reactive protein, albumin levels) 4
• Exclude superimposed bacterial or viral infections before escalating therapy 2, 4

Rescue Therapy

If patients do not sufficiently respond to IV corticosteroids after 3-5 days, initiate rescue treatment with ciclosporin or infliximab. 4

• Monitor symptoms closely along with serum C-reactive protein and albumin levels 4
• If medical therapy fails, perform timely colectomy to prevent critical complications 4
• Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding 5

Critical Pitfalls to Avoid

• Always exclude infectious causes of diarrhea before attributing symptoms to UC flare and escalating therapy 6
• Rapid steroid tapering is associated with early relapse—taper prednisolone over 6-8 weeks, not faster 1, 6
• For distal UC, address proximal constipation with laxatives, as it can paradoxically worsen diarrhea symptoms 6
• Patients who do not respond by Week 14 to treatment are unlikely to respond with continued dosing 3
• Regular monitoring of renal function is recommended for patients on long-term 5-ASA therapy (eGFR before starting, after 2-3 months, then annually) 2

Maintenance After Flare Resolution

After achieving remission, continue maintenance therapy with mesalazine to prevent relapse. 2

• Lifelong maintenance therapy is generally recommended, especially for those with left-sided or extensive disease 2, 6
• For patients with chronic active steroid-dependent disease, use azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day 6