What is the best current treatment for ulcerative colitis?

Best Current Treatment for Ulcerative Colitis

The best current treatment for ulcerative colitis is a stepwise approach based on disease severity, with infliximab and vedolizumab as preferred first-line biologics for moderate-to-severe disease, and upadacitinib emerging as the most effective therapy for both biologic-naïve and biologic-exposed populations. 1

Treatment Algorithm Based on Disease Severity

Mild to Moderate Disease

1. First-line therapy: Combination of oral mesalazine ≥2.4 g/day plus topical mesalazine 1 g/day 2

   • Once-daily dosing is as effective as divided doses
   • Topical formulation should match the extent of disease

2. If no improvement within 10-14 days or no complete relief after 40 days:

   • Add oral systemic corticosteroids 2

3. Maintenance therapy:

   • Lifelong maintenance with oral mesalazine 2-4g daily to prevent relapse and reduce colorectal cancer risk 2
   • Azathioprine or mercaptopurine for those who cannot maintain remission on 5-ASA compounds 2

Moderate to Severe Disease

1. Preferred first-line biologics (based on network meta-analysis):

   • Infliximab (5 mg/kg at 0,2, and 6 weeks, then every 8 weeks) 1, 3
   • Vedolizumab 1
   • These are preferred over standard-dose adalimumab or golimumab 1

2. For patients with prior exposure to infliximab:

   • Vedolizumab or tofacitinib may be preferred over adalimumab or golimumab 1
   • Upadacitinib has shown superior efficacy in both biologic-naïve and biologic-exposed populations 1

3. Combination therapy:

   • Biologic agent with an immunomodulator is more effective than monotherapy with either agent 1
   • Consider risk-benefit profile for individual patients

Severe Acute Ulcerative Colitis (ASUC)

1. Initial management:

   • Hospitalization
   • IV methylprednisolone 60 mg/day or hydrocortisone 100 mg four times daily 1
   • IV fluid and electrolyte replacement
   • Potassium supplementation (at least 60 mmol/day)
   • Thromboprophylaxis with low-molecular-weight heparin 1
   • Blood transfusion if needed to maintain hemoglobin above 8-10 g/dl 1

2. Assessment at day 3 of IV steroids:

   • If no improvement, consider rescue therapy or surgery 1

3. Rescue therapy options for steroid-refractory disease:

   • Infliximab or cyclosporine (equally effective) 1
   • Tacrolimus as an alternative 1

4. Surgical indications:

   • Free perforation
   • Life-threatening hemorrhage
   • Toxic megacolon with clinical deterioration
   • No improvement after 4-7 days of salvage therapy 1, 2

Important Considerations

Monitoring and Assessment

• Regular monitoring of disease activity through clinical symptoms, laboratory parameters, and endoscopic evaluation
• Surveillance colonoscopies to monitor for dysplasia/cancer 2

Emerging Therapies

• Upadacitinib has demonstrated superior efficacy compared to other biologics, though long-term safety data is still being collected 1
• Fecal transplantation shows promise in small studies but requires additional research to define optimal protocols 1

Common Pitfalls to Avoid

1. Inadequate dosing of 5-ASA compounds 2
2. Prolonged steroid use without appropriate steroid-sparing strategies 2
3. Delayed surgical consultation in severe cases 2
4. Failure to exclude infectious causes of colitis exacerbation 2
5. Inappropriate use of opioids for pain management, which can worsen gut dysmotility 2

Special Considerations

• Patients on TNF inhibitors should be screened for tuberculosis prior to treatment 3
• Combination of TNF inhibitors with thiopurines (azathioprine/6-mercaptopurine) increases efficacy but may increase risk of hepatosplenic T-cell lymphoma, particularly in young males 3
• Patients who fail to respond to biologics by week 14 are unlikely to respond with continued dosing 3

The treatment of ulcerative colitis continues to evolve, with an increasing focus on personalized therapy based on individual patient characteristics, disease phenotype, and biomarkers to predict treatment response.