How does Skyrizi (Risankizumab) affect patients with a history of Human Papillomavirus (HPV)?

Skyrizi (Risankizumab) and HPV: Impact on Patients with HPV History

Skyrizi (risankizumab) may potentially increase the risk of HPV persistence or reactivation in patients with a history of HPV infection due to its immunosuppressive effects, requiring careful monitoring and preventive measures.

Mechanism of Concern

Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 (IL-23) by targeting the p19 subunit 1. This immunomodulatory mechanism has implications for viral infections:

• IL-23 plays an important role in immune surveillance against viral infections
• Immune suppression is a known risk factor for HPV persistence and progression 2
• Patients with compromised immune systems have more difficulty clearing HPV infections

HPV Natural History and Immune Response

Understanding HPV's natural history helps explain the potential risk:

• Most HPV infections (70%) clear within 1 year and approximately 90% clear within 2 years through normal immune function 2
• Persistent infection with high-risk HPV types is the primary risk factor for cervical cancer precursors and invasive cervical cancer 2
• The immune system plays a critical role in controlling HPV infection:
  • Innate immune cells (macrophages, natural killer cells)
  • Adaptive immune cells (dendritic cells, CD4+/CD8+ T cells) 3
• Immunosuppression can disrupt the balance between Th1 and Th2 cells and downregulate dendritic cell activation 3

Clinical Implications for Patients on Skyrizi

While there are no specific studies directly examining Skyrizi's effect on HPV, the following clinical approach is recommended:

1. Pre-treatment screening:

   • Ensure patients are up-to-date with appropriate HPV screening
   • Consider HPV vaccination status and complete vaccination if appropriate 4

2. Monitoring during treatment:

   • Maintain regular cervical cancer screening as recommended by guidelines 2
   • Annual digital anorectal examination (DARE) may be considered for high-risk patients 2
   • Monitor for any new or changing genital warts

3. Patient education:

   • Inform patients about potential increased risk of HPV persistence
   • Emphasize importance of regular screening
   • Advise on safe sexual practices to prevent new HPV exposures 2

Management of HPV-Related Conditions in Patients on Skyrizi

If HPV-related conditions develop during Skyrizi treatment:

• For genital warts:

  • Standard treatments apply (provider-administered therapies like cryotherapy, TCA, or surgical removal; or patient-applied therapies like podofilox or imiquimod) 2
  • May require more frequent treatment cycles due to potentially compromised immune response

• For cervical/anal dysplasia:

  • Follow standard management protocols with potentially closer surveillance
  • Consider the risk-benefit of continuing Skyrizi in patients with high-grade lesions

Prevention Strategies

For patients starting or continuing Skyrizi with a history of HPV:

• HPV vaccination should be considered if not previously completed, ideally before starting treatment 4
• Prophylactic HPV vaccination may help prevent new HPV infections or reinfection with the same HPV type 4
• Regular screening is essential for early detection of any HPV-related disease progression

Safety Profile of Skyrizi

Long-term safety data for Skyrizi is reassuring but requires context:

• In the LIMMitless phase 3 extension trial (6 years of continuous treatment), Skyrizi demonstrated a favorable safety profile 5
• Treatment-emergent adverse events remained low and consistent with rates observed in previous studies 5
• However, specific monitoring for HPV-related outcomes was not a primary focus of these trials

Key Considerations and Pitfalls

• Don't assume HPV will clear normally: While most immunocompetent individuals clear HPV infections, immunosuppression may alter this natural history
• Don't neglect screening: Maintain or increase the frequency of appropriate HPV-related screening
• Don't overlook vaccination: Consider HPV vaccination even in patients with prior HPV infection, as it may prevent new infections with different HPV types 4
• Don't ignore new lesions: Any new genital warts or abnormal screening results should be promptly evaluated

In conclusion, while Skyrizi has demonstrated excellent efficacy for approved indications like psoriasis, clinicians should maintain vigilance regarding potential HPV-related complications in patients with a history of HPV infection.