Does Skyrizi Increase Risk of Shingles?
Skyrizi (risankizumab) does carry a risk of herpes zoster (shingles), but this risk appears to be lower than with JAK inhibitors and similar to or potentially lower than with TNF inhibitors. According to the FDA label, serious infections in the Skyrizi group included herpes zoster, though the overall infection rates were not dramatically elevated compared to placebo 1.
Evidence from Clinical Trials
In plaque psoriasis trials through Week 52, herpes zoster was identified as a serious infection in patients receiving Skyrizi, though specific incidence rates were not substantially higher than background rates 1. The FDA label lists infections as occurring in 22.1% of the Skyrizi group (90.8 events per 100 subject-years) compared with 14.7% of the placebo group (56.5 events per 100 subject-years) in the first 16 weeks, with serious infections including herpes zoster 1.
Comparison with Other Biologics
The risk profile differs significantly from JAK inhibitors, which show substantially elevated herpes zoster rates:
JAK inhibitors demonstrate incidence rates of 3-4 per 100 patient-years in Western populations and up to 9 per 100 patient-years in Japan and Korea, compared to 2-3 per 100 patient-years for TNF inhibitors 2.
TNF inhibitors (particularly monoclonal antibodies like infliximab and adalimumab) show increased herpes zoster risk with registry data indicating elevated rates compared to conventional DMARDs 2, 3. Specifically, monoclonal anti-TNF-alpha antibodies showed a crude incidence rate of 11.1 per 1000 patient-years versus 5.6 for conventional DMARDs 3.
IL-23 inhibitors like risankizumab (Skyrizi) have not demonstrated the same magnitude of herpes zoster risk as JAK inhibitors or TNF inhibitors 4, 5.
Clinical Implications and Monitoring
Patients should be counseled that while herpes zoster can occur with Skyrizi, the risk is manageable and does not require routine antiviral prophylaxis 1. The FDA label instructs patients to contact their healthcare provider if they develop symptoms of infection, including those consistent with shingles 1.
If herpes zoster develops during Skyrizi treatment:
- Initiate antiviral therapy promptly with acyclovir, valacyclovir, or famciclovir 6
- Consider temporarily holding Skyrizi until the infection resolves, though this is not explicitly mandated in the label 6
- Monitor for complete healing before resuming therapy 6
Vaccination Considerations
The recombinant zoster vaccine (Shingrix) should be considered before initiating Skyrizi therapy 7, 8. This non-live vaccine is safe for immunocompromised patients and reduces herpes zoster risk by approximately 81% across immunocompromised populations 8.
Live zoster vaccines (Zostavax) should be avoided during Skyrizi treatment, as the FDA label states that live vaccines are not recommended during or immediately before/after treatment 1. The recombinant vaccine can be administered at any time, including during active Skyrizi therapy 7.
Risk Stratification
Higher risk patients include:
- Those over age 65 years 2
- Patients receiving concomitant glucocorticoids ≥7.5 mg/day 2
- Female patients 2
- Asian populations (particularly Japanese and Korean patients, though this data is primarily from JAK inhibitor studies) 2
The overall herpes zoster risk with Skyrizi is substantially lower than with JAK inhibitors and appears comparable to or potentially lower than TNF inhibitors, making it a reasonable choice for patients concerned about viral reactivation risk 4, 5.