Are patients on Skyrizi (Risankizumab) considered immunocompromised?

Are Patients on Skyrizi (Risankizumab) Considered Immunocompromised?

Patients on Skyrizi (risankizumab) should be considered moderately immunocompromised due to its mechanism of IL-23 inhibition, which affects immune function. 1

Understanding Risankizumab's Immunomodulatory Effects

Risankizumab is a fully human IgG1 lambda monoclonal antibody that selectively inhibits interleukin-23 (IL-23) by binding to the p19 subunit. This targeted immunomodulation has implications for immune function:

• IL-23 inhibitors like Skyrizi affect specific immune pathways rather than causing broad immunosuppression
• Guidelines specifically recommend using caution in patients with pre-existing immunosuppression-related conditions when using IL-23 inhibitors 1
• The degree of immunocompromise is generally considered moderate compared to other immunosuppressive agents

Clinical Implications of Immunocompromised Status

Infection Risk

While Skyrizi has a favorable safety profile, its immunomodulatory effects warrant certain precautions:

• Patients should be monitored for signs of infection during treatment
• The FDA label does not list specific warnings about severe infections, unlike some other biologics 2
• Clinical trials have shown similar rates of serious infections between risankizumab and placebo groups (1.0% vs 1.2%) 3

Vaccination Considerations

Immunization strategies should be modified for patients on Skyrizi:

• Live vaccines should be avoided in patients on immunosuppressive therapy 1
• Inactivated vaccines can be administered, but immune response may be suboptimal
• Ideally, vaccinations should be completed before initiating Skyrizi therapy when possible
• For herpes zoster protection, the recombinant zoster vaccine (RZV) is preferred over the live zoster vaccine (ZVL) for patients on immunomodulatory therapy 1

Comparison to Other Immunomodulatory Therapies

The degree of immunocompromise with Skyrizi appears to be less severe than with:

• TNF-α inhibitors
• High-dose corticosteroids (>20 mg/day of prednisone or equivalent) 1
• Combination immunosuppressive regimens

Practical Management Approach

1. Before starting Skyrizi:

   • Screen for latent infections
   • Update vaccinations when possible
   • Assess baseline immune function

2. During Skyrizi treatment:

   • Monitor for signs of infection
   • Consider prophylaxis for patients with recurrent infections
   • Exercise caution with live vaccines

3. Special situations:

   • For surgery: No specific recommendations to discontinue Skyrizi
   • For exposure to infectious diseases: Consider the patient moderately immunocompromised when determining prophylaxis needs

Common Pitfalls to Avoid

• Underestimating immune status: While Skyrizi has a targeted mechanism, patients should still be considered immunocompromised
• Inappropriate vaccination: Administering live vaccines to patients on Skyrizi could lead to vaccine-related infections
• Ignoring signs of infection: Immunomodulation may blunt typical inflammatory responses, potentially masking infection symptoms

In conclusion, patients on Skyrizi should be managed as moderately immunocompromised individuals, with appropriate infection prevention strategies and vaccination modifications, though the specific risk appears lower than with broader immunosuppressive agents.