What are the treatment options for colitis?

Treatment of Colitis

For mild to moderate ulcerative colitis, start with oral mesalamine ≥2.4g daily combined with topical mesalamine 1g daily as first-line therapy, escalating to oral prednisolone 40mg daily if there is inadequate response. 1

Treatment Strategy Based on Disease Extent and Severity

Treatment must be tailored based on three key factors: disease extent (proctitis, left-sided, or extensive/pancolitis), disease severity (mild, moderate, or severe), and response to prior therapies. 2

Proctitis (Rectal Disease Only)

• Mesalamine 1g suppository once daily is the preferred initial treatment for mild to moderately active proctitis, as suppositories deliver drug more effectively to the rectum than foam or enemas. 2
• Topical mesalamine is superior to topical corticosteroids and should be the preferred topical agent. 1
• Combining topical mesalamine with oral mesalamine (≥2.4g daily) or topical steroids increases efficacy beyond monotherapy. 2, 1
• Refractory proctitis requires escalation to systemic steroids, immunosuppressants, and/or biologics. 2

Left-Sided/Sigmoid Colitis

• Combination therapy with oral mesalamine 2-4g daily plus topical mesalamine 1g daily is more effective than either agent alone and should be the initial approach. 1, 3
• Topical formulation selection matters: use suppositories for disease limited to rectum, foam or liquid enemas for more proximal left-sided disease. 1
• Once-daily dosing with mesalamine is as effective as divided doses, which may improve adherence. 1

Extensive Colitis/Pancolitis

• Oral mesalamine 2-4g daily combined with topical mesalamine enemas 1g daily is the cornerstone of initial therapy for mild to moderate disease. 1, 4
• Standard-dose mesalamine (2-3g/day) or diazo-bonded 5-ASA should be used as initial therapy. 3
• Alternative aminosalicylates include balsalazide 6.75g daily or olsalazine 1.5-3g daily, though sulfasalazine (2-4g daily) has higher side effect rates. 1, 4

Escalation for Inadequate Response to Aminosalicylates

Moderate Disease Without Response

• If standard-dose mesalamine fails, increase to high-dose mesalamine (>3g/day or up to 4.8g/day) with rectal mesalamine before escalating to corticosteroids. 3, 5
• If insufficient response persists after optimized aminosalicylate therapy, initiate oral prednisolone 40mg daily. 1, 4
• Prednisolone should be tapered gradually over approximately 8 weeks according to patient response. 1, 4

Moderate to Severe Disease

• Systemic corticosteroids (prednisolone 40mg daily) are appropriate for moderate to severe disease or for patients with mild disease who don't respond to mesalamine. 1
• For patients at high risk of colectomy with moderate-severe disease activity, biologic agents with or without an immunomodulator, or tofacitinib, should be used early rather than gradual step-up therapy after failure of 5-aminosalicylates. 2

Biologic Therapy for Moderate to Severe Disease

First-Line Biologic Selection

• Infliximab and vedolizumab may be preferred first-line therapy in biologic-naïve patients, rather than standard-dose adalimumab or golimumab, based on network meta-analysis. 2
• Infliximab is FDA-approved for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing in moderately to severely active ulcerative colitis with inadequate response to conventional therapy. 6
• Infliximab dosing: 5mg/kg IV at weeks 0,2, and 6, then every 8 weeks for maintenance. 6

Prior Biologic Exposure

• In patients with prior exposure to infliximab, particularly those with primary non-response to induction therapy, vedolizumab or tofacitinib may be preferred over adalimumab or golimumab. 2

Combination vs. Monotherapy

• Combination therapy of a biologic agent with an immunomodulator is more effective than monotherapy with either agent. 2
• However, patients with less severe disease and those averse to medication side effects may opt for monotherapy. 2

Severe/Acute Severe Ulcerative Colitis (ASUC)

Hospital Management

• Severe ulcerative colitis requires hospital admission and joint management by gastroenterologist and colorectal surgeon. 1, 4
• Severe UC is defined by bloody stool frequency ≥6/day plus one additional criterion: tachycardia (>90/min), temperature >37.8°C, anemia (hemoglobin <10.5 g/dL), or ESR >30 mm/h (or CRP >30 mg/L). 2

Acute Treatment

• Intravenous methylprednisolone 40-60mg/day (or equivalent) is the mainstay of therapy after excluding alternative etiologies. 2
• Routine use of adjunctive antibiotics in patients without infections is not recommended. 2
• Supportive care includes IV fluid and electrolyte replacement, blood transfusion to maintain hemoglobin >10 g/dL, subcutaneous heparin for thromboembolism prophylaxis, and nutritional support if malnourished. 4

Steroid-Refractory Disease

• Patients refractory to 3-5 days trial of intravenous corticosteroids who prefer ongoing medical management may be treated with either infliximab or cyclosporine. 2

Maintenance Therapy

Long-Term Management

• Lifelong maintenance therapy is generally recommended, especially for left-sided or extensive disease. 1, 3, 4
• Aminosalicylates are effective and safe for maintenance therapy. 1, 3
• Patients in remission with biologic agents and/or immunomodulators or tofacitinib after prior failure of 5-ASA may discontinue 5-aminosalicylates. 2

Steroid-Dependent Disease

• For steroid-dependent disease, consider immunomodulators: azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day. 1, 4
• Thiopurine monotherapy should not be used for induction of remission but may be considered for maintenance of remission. 2
• Long-term steroid treatment should be avoided due to significant side effects. 4

Special Considerations and Pitfalls

Critical Warnings with Biologics

• Increased risk of serious infections including tuberculosis, bacterial sepsis, and invasive fungal infections—perform latent TB testing before initiating infliximab and monitor all patients for active TB during treatment. 6
• Lymphoma and other malignancies, including fatal hepatosplenic T-cell lymphoma (HSTCL), have been reported, particularly in adolescent and young adult males with Crohn's disease or ulcerative colitis receiving concomitant azathioprine or 6-mercaptopurine. 6

Common Management Pitfalls

• Avoid antidiarrheal medications, as they can mask worsening symptoms while allowing underlying inflammation to progress, with theoretical risk of precipitating toxic megacolon. 4
• Proximal constipation should be treated with stool bulking agents or laxatives, not antidiarrheals. 1, 4
• Patients who do not respond by week 14 of biologic therapy are unlikely to respond with continued dosing and consideration should be given to discontinue treatment. 6

Microscopic Colitis

• Budesonide 9mg daily is first-line therapy over mesalamine or no treatment for symptomatic microscopic colitis, with high-quality evidence supporting this recommendation. 3