What is the treatment approach for a patient with colitis, considering their past medical history and potential need for medication to induce remission?

Treatment of Colitis

For moderate-to-severe ulcerative colitis, initiate advanced therapy with infliximab, risankizumab, guselkumab, or ozanimod as first-line agents in biologic-naïve patients, as these demonstrate superior efficacy for inducing clinical remission compared to adalimumab. 1

Disease Severity Classification

Before initiating treatment, classify disease severity and extent:

• Mild-to-moderate disease: Bloody diarrhea with manageable symptoms, no systemic signs 2
• Moderate-to-severe disease: Mayo endoscopy sub-score 2-3, or mild symptoms with high inflammatory burden, or corticosteroid-dependent disease 2
• Acute severe colitis: Bloody stool frequency ≥6/day plus at least one of: tachycardia >90/min, temperature >37.8°C, hemoglobin <10.5 g/dL, or ESR >30 mm/h (CRP >30 mg/L) 3

Treatment Algorithm by Disease Extent and Severity

Ulcerative Proctitis (Rectal Disease Only)

• First-line: Mesalazine 1g suppository once daily 2, 4
• Suppositories are superior to enemas for proctitis as they better target the site of inflammation and are better tolerated 4
• Second-line (if refractory): Add rectal corticosteroids (budesonide or hydrocortisone foam) 4
• Combining rectal 5-ASA with rectal corticosteroids is superior to either agent alone for refractory disease 4

Left-Sided or Extensive Colitis (Mild-to-Moderate)

• First-line: Combination therapy with topical mesalazine 1g daily PLUS oral mesalamine 2-4g daily 2
• This combination achieves superior remission rates compared to monotherapy 2
• Once-daily dosing of topical mesalazine is as effective as divided doses 4
• Second-line: Add oral corticosteroids (prednisolone 40mg daily, tapered over 8 weeks) if inadequate response 1

Moderate-to-Severe Colitis (Biologic-Naïve Patients)

In the United States (where JAK inhibitors are restricted as first-line):

• Preferred first-line agents (in order of efficacy): 1

  • Infliximab 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 5
  • Risankizumab
  • Guselkumab
  • Ozanimod
  • Golimumab

• These agents demonstrate possibly higher likelihood of achieving remission compared to adalimumab with low-certainty evidence 1

Outside the United States (where JAK inhibitors permitted first-line):

• Upadacitinib shows the greatest effect size, achieving remission in approximately 50% of patients 1
• Risankizumab and ozanimod also demonstrate high efficacy 1

Moderate-to-Severe Colitis (Biologic-Exposed Patients)

• After infliximab failure (especially primary non-response): Use ustekinumab or tofacitinib rather than vedolizumab or adalimumab 1
• Consider switching out of class when there is lack of response despite adequate drug concentration 3

Acute Severe Colitis (Hospitalized Patients)

Initial management:

• IV corticosteroids: Methylprednisolone 40-60mg/day (preferred over hydrocortisone due to less mineralocorticoid effect) 1, 2
• Approximately 67% respond to IV corticosteroids alone 2
• Supportive care: 2
  • IV fluid and electrolyte replacement with potassium supplementation ≥60 mmol/day
  • Low-molecular-weight heparin for thromboprophylaxis (rectal bleeding is NOT a contraindication)
  • Nutritional support if malnourished
  • Daily monitoring: stool frequency, vital signs, CBC, CRP, albumin, electrolytes

Rescue therapy (if inadequate response by day 3-5):

• Infliximab 5 mg/kg IV OR cyclosporine 2 mg/kg/day 1, 2
• Limit IV corticosteroid duration to maximum 7-10 days (prolonged courses increase toxicity without additional benefit) 2

Surgical indications:

• Failure to improve or deterioration within 48-72 hours 3
• Free perforation, life-threatening hemorrhage, or generalized peritonitis 3
• Toxic megacolon with perforation, massive bleeding, or clinical deterioration 3
• Subtotal colectomy with ileostomy is the preferred emergency surgical approach 3

Combination Therapy Considerations

For patients on biologic therapy:

• Combine TNF antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate rather than using biologic monotherapy 1, 2
• Combination therapy is superior for inducing remission, though patients with less severe disease who prioritize safety may reasonably choose monotherapy 1

Maintenance Therapy

Once remission is achieved:

• Continue lifelong maintenance therapy with aminosalicylates (≥2g/day), azathioprine, or mercaptopurine 1, 2
• For patients on combination therapy (TNF antagonist + immunomodulator) in corticosteroid-free remission for ≥6 months, do NOT withdraw the TNF antagonist 2
• Discontinue 5-aminosalicylates in patients who achieved remission with biologic agents and/or immunomodulators, as they provide no additional benefit 1
• Maintenance mesalamine can be accomplished with twice-weekly enemas or enemas one week per month when using 4g/day dose 4

Critical Pitfalls to Avoid

• Do NOT use thiopurine monotherapy for induction of remission in active moderate-severe disease (use biologic monotherapy or tofacitinib instead) 1
• Do NOT use methotrexate monotherapy for induction or maintenance of UC 1
• Do NOT use corticosteroids for long-term maintenance due to significant adverse effects 3
• Do NOT delay surgery in critically ill patients with toxic megacolon, as this increases perforation risk with high mortality 3
• Do NOT switch between different oral 5-ASA formulations if initial therapy fails, as this is ineffective 2
• Assess for proximal constipation with abdominal X-ray before declaring treatment failure, as fecal loading impairs drug delivery 4
• Screen for latent tuberculosis before initiating infliximab, as treatment for latent infection must be initiated prior to use 5
• Avoid adjunctive antibiotics in hospitalized patients with acute severe UC without documented infections 1

Special Monitoring Requirements

For infliximab therapy:

• Monitor closely for infections during and after treatment, including possible development of tuberculosis in patients who tested negative for latent TB prior to therapy 5
• Be aware of increased risk of lymphoma and other malignancies, particularly hepatosplenic T-cell lymphoma in adolescent and young adult males receiving concomitant azathioprine or 6-mercaptopurine 5
• Consider invasive fungal infections (histoplasmosis, coccidioidomycosis) in patients who develop severe systemic illness, as antigen/antibody testing may be negative 5