Which IBD (Inflammatory Bowel Disease) medication would you avoid in a patient with moderate ulcerative colitis (UC) due to concerns about systemic immunosuppression?

Medications to Avoid in Moderate UC When Concerned About Systemic Immunosuppression

For patients with moderate ulcerative colitis where systemic immunosuppression is a concern, thiopurines (azathioprine, 6-mercaptopurine) should be avoided as they offer limited efficacy with significant immunosuppressive risk. 1

Rationale for Avoiding Thiopurines

• The 2024 AGA guidelines specifically suggest against using thiopurine monotherapy for inducing remission in patients with active UC (conditional recommendation; very low certainty of evidence) 1
• Thiopurines have a poor risk-benefit profile when systemic immunosuppression is a concern:
  • Limited efficacy for induction of remission
  • Significant systemic immunosuppressive effects
  • Associated with increased risk of opportunistic infections and malignancies
  • Slow onset of action (3-6 months)

Alternative Medication Options with Less Systemic Immunosuppression

Preferred Options

1. Vedolizumab

   • Gut-selective anti-integrin biologic with minimal systemic immunosuppression
   • AGA recommends vedolizumab for moderate-to-severe UC (strong recommendation) 1
   • Associated with lower rates of infectious complications than TNF antagonists 1

2. S1P Receptor Modulators (ozanimod, etrasimod)

   • More targeted mechanism with potentially less systemic immunosuppression
   • AGA recommends ozanimod and etrasimod for moderate-to-severe UC 1

Other Options to Consider

• 5-ASA compounds (mesalamine) - may be insufficient for moderate UC but have minimal immunosuppressive effects
• Ustekinumab - targets IL-12/23 pathway with potentially less systemic immunosuppression than TNF inhibitors

Medications with Significant Systemic Immunosuppression to Consider Carefully

1. TNF Antagonists (infliximab, adalimumab, golimumab)

   • Effective but associated with significant systemic immunosuppression
   • Higher risk of opportunistic infections compared to vedolizumab 1

2. JAK Inhibitors (tofacitinib, upadacitinib, filgotinib)

   • Broad immunosuppressive effects
   • FDA recommends use only after TNF antagonist failure 1
   • Associated with increased risk of serious infections, herpes zoster, and potentially cardiovascular events

3. Methotrexate

   • AGA suggests against using methotrexate monotherapy for induction or maintenance of remission 1
   • Limited efficacy with significant immunosuppressive potential

Clinical Decision-Making Algorithm

1. Assess severity and extent of UC

   • Confirm moderate disease activity through symptoms, biomarkers, and endoscopic evaluation
   • Evaluate comorbidities that might increase risk from immunosuppression

2. Consider vedolizumab as first-line therapy

   • Gut-selective mechanism minimizes systemic immunosuppression
   • Strong recommendation from AGA for moderate-to-severe UC 1

3. If vedolizumab is not suitable:

   • Consider S1P receptor modulators (ozanimod, etrasimod)
   • Evaluate ustekinumab as an alternative option

4. Avoid combination therapy with immunomodulators

   • While combination therapy of biologics with immunomodulators is more effective, it significantly increases immunosuppression risk 1

Important Considerations

• Ensure appropriate pre-treatment screening (tuberculosis, hepatitis B, etc.) before initiating any biologic therapy 1
• Consider vaccination status (influenza, pneumococcal, herpes zoster) before initiating therapy 1
• Monitor for treatment response and adjust therapy accordingly
• The choice of medication should balance efficacy against the specific immunosuppression concerns for the individual patient