What are the considerations for using adalimumab (adalimumab), guselkumab (guselkumab), or risankizumab (risankizumab) in a patient with moderate ulcerative colitis (UC) where systemic immunosuppression is a concern?

Adalimumab, Guselkumab, and Risankizumab in Moderate Ulcerative Colitis with Immunosuppression Concerns

For patients with moderate ulcerative colitis where systemic immunosuppression is a concern, vedolizumab is the preferred first-line therapy due to its gut-selective mechanism that minimizes systemic immunosuppression, while adalimumab should be avoided due to its lower efficacy and significant systemic immunosuppressive effects. 1, 2

Comparative Efficacy and Safety Profile

Adalimumab

• Efficacy: Considered a LOWER efficacy medication by the AGA for moderate-to-severe UC 1
• Immunosuppression risk: High systemic immunosuppression with increased risk of opportunistic infections 2
• Clinical remission rates: Modest efficacy with clinical remission rates of 16.5% at week 8 and 17.3% at week 52 3
• Best use case: May be appropriate for patients who prefer self-injection and have moderate disease activity, but not ideal when immunosuppression is a concern 4

Guselkumab (IL-23 antagonist)

• Efficacy: Classified as a HIGHER efficacy medication by the AGA for biologic-naïve patients 1
• Immunosuppression risk: Lower rate of infectious complications compared to TNF antagonists like adalimumab 1, 2
• Clinical positioning: Demonstrated "possibly important benefit" over adalimumab in network meta-analysis 1
• Best use case: Good option when immunosuppression is a concern due to more targeted mechanism of action 2

Risankizumab (IL-23 antagonist)

• Efficacy: Classified as a HIGHER efficacy medication for biologic-naïve patients 1
• Immunosuppression risk: Lower rate of infectious complications compared to TNF antagonists 1, 2
• Clinical positioning: Likely has "important benefit" compared to adalimumab with moderate certainty evidence 1
• Best use case: Excellent option when immunosuppression is a concern due to more targeted mechanism 2

Decision Algorithm for Patients with Immunosuppression Concerns

1. First-line option: Vedolizumab

   • Gut-selective mechanism with minimal systemic immunosuppression
   • Strong recommendation from AGA for moderate-to-severe UC 2
   • Preferred in patients at higher risk of immunosuppression-related infections 1

2. Second-line options (if vedolizumab not suitable):

   • Risankizumab or Guselkumab (IL-23 antagonists)
     • Higher efficacy than adalimumab 1
     • More targeted mechanism with lower immunosuppressive risk 2
     • Risankizumab shows "likely important benefit" over adalimumab with moderate certainty evidence 1

3. Avoid if possible:

   • Adalimumab
     • Lower efficacy compared to other options 1
     • Higher systemic immunosuppression risk 2
     • Classified as a "LOWER efficacy medication" by the AGA 1

Important Clinical Considerations

• Pre-treatment screening: Ensure appropriate screening for tuberculosis, hepatitis B, and other infections before initiating any biologic therapy 2

• Vaccination status: Update vaccinations (influenza, pneumococcal, herpes zoster) before starting therapy 2

• Monitoring: Regular monitoring for treatment response and adverse effects is essential, with particular attention to signs of infection in immunosuppressed patients

• Combination therapy: Avoid combination with immunomodulators when immunosuppression is a concern, as this significantly increases immunosuppression risk 2

• Dose considerations: Higher induction doses may be required for patients with more severe disease, but this must be balanced against immunosuppression concerns 4

Common Pitfalls to Avoid

1. Underestimating immunosuppression risk: TNF antagonists like adalimumab carry higher risk of serious infections compared to gut-selective or more targeted therapies 2

2. Inadequate pre-treatment screening: Failure to screen for latent infections can lead to serious complications when initiating immunosuppressive therapy

3. Inappropriate combination therapy: Adding immunomodulators to biologics significantly increases immunosuppression risk and should be avoided when immunosuppression is already a concern 2

4. Overlooking patient-specific factors: Age, comorbidities, prior infections, and malignancy history should all factor into the decision-making process