What is the treatment for a mild to moderate ulcerative colitis flare-up?

Treatment for Ulcerative Colitis Flare-Up

Start with standard-dose oral mesalamine (2-3 grams/day) or diazo-bonded 5-ASA as first-line therapy for mild to moderate ulcerative colitis flare-ups, and add rectal mesalamine to enhance efficacy, particularly for extensive or left-sided disease. 1, 2

Initial Treatment Strategy by Disease Location

Extensive or Left-Sided Disease

• Begin with standard-dose oral mesalamine (2-3 grams/day) or diazo-bonded 5-ASA (such as balsalazide or olsalazine), which is superior to low-dose mesalamine, sulfasalazine, or no treatment 1
• Add rectal mesalamine to oral therapy to improve induction of remission rates—combination therapy is more effective than either alone 1, 2, 3
• Once-daily dosing is preferred over multiple daily doses for convenience without loss of efficacy 1

Proctosigmoiditis (Left-Sided Distal Disease)

• Use mesalamine enemas (≥1 gram daily) rather than oral mesalamine as first-line therapy 1, 3
• Mesalamine enemas are preferred over rectal corticosteroids for superior effectiveness 1
• Patients prioritizing convenience over maximal effectiveness may reasonably choose oral mesalamine 1

Proctitis (Rectal Disease Only)

• Mesalamine suppositories (1 gram once daily) are the most effective initial treatment with strong recommendation and moderate-quality evidence 1, 2, 3
• This is superior to oral mesalamine for isolated rectal inflammation 1

Dose Escalation for Inadequate Response

If patients show suboptimal response to standard-dose therapy after 10-14 days, or present with moderate disease activity at onset, escalate to high-dose mesalamine (>3 grams/day) combined with rectal mesalamine. 1, 2

• High-dose oral mesalamine is more effective than standard doses for moderate disease activity 2, 4
• Do not switch between different oral 5-ASA formulations when initial therapy fails—instead, escalate dose or add rectal therapy 2

Management of Refractory Disease

For patients refractory to optimized oral and rectal 5-ASA therapy (defined as persistent symptoms beyond 10-14 days despite appropriate mesalamine therapy), add either oral prednisone (40 mg daily) or budesonide MMX. 1, 2, 3

• This applies regardless of disease extent 1
• Corticosteroids should only be added after optimized mesalamine therapy has failed, not as first-line treatment 3
• The European guidelines suggest waiting up to 40 days of appropriate 5-ASA therapy before adding prednisolone if sustained relief has not been achieved 3

Alternative Options for Rectal Therapy Intolerance

If patients are intolerant of or refractory to mesalamine suppositories or enemas, use rectal corticosteroid therapy (enemas or foams) rather than no therapy. 1

• Patients who place higher value on avoiding difficulties with mesalamine enemas may reasonably select rectal corticosteroid foam preparations 1
• However, topical mesalamine remains superior to topical corticosteroids for inducing remission 3

Monitoring Requirements

• Monitor renal function periodically in all patients on 5-ASA therapy due to rare but serious risk of interstitial nephritis 2, 5
• Monitor complete blood cell counts and platelet counts, particularly in elderly patients (≥65 years), due to higher incidence of blood dyscrasias 5
• Discontinue mesalamine if renal function deteriorates during therapy 5

Critical Pitfalls to Avoid

• Do not use low-dose mesalamine (<2 grams/day) for active disease—start with standard or high doses 1
• Do not use rectal corticosteroids as first-line therapy instead of mesalamine suppositories for proctitis 2
• Do not delay escalation to corticosteroids if rectal bleeding persists beyond 10-14 days despite optimized mesalamine therapy 3
• Avoid rectal suppositories and enemas in patients with suspected mechanical bowel obstruction 2
• Do not use probiotics, curcumin, or fecal microbiota transplantation outside of clinical trials, as these lack evidence and risk delaying proven effective therapy 1

Medication Formulations

Mesalamine preparations include: 2

• Delayed-release enteric-coated tablets (pH-sensitive release in distal ileum and colon)
• Controlled-release formulations (delivery from duodenum to lower bowel)
• MMX formulation (delayed and extended delivery throughout lower bowel)
• Capsules containing delayed enteric-coated granules

Diazo-bonded 5-ASA includes: 2

• Olsalazine (two 5-ASA moieties joined by azo bond)
• Balsalazide (one 5-ASA moiety linked to inert carrier)

Rare but Serious Adverse Effects

• Idiosyncratic worsening of colitis (presumed hypersensitivity syndrome) 2
• Interstitial nephritis 2, 5
• Secretory diarrhea (primarily with olsalazine) 2
• Blood dyscrasias (agranulocytosis, neutropenia, pancytopenia), particularly in elderly patients 5