What antiviral prophylaxis is recommended for pediatric patients on Janus Kinase (JAK) inhibitors?

Antiviral Prophylaxis for Pediatric Patients on JAK Inhibitors

Pediatric patients on JAK inhibitors should receive prophylaxis against herpes zoster virus (HZV) due to their increased risk of viral reactivation, with acyclovir or valacyclovir being the recommended agents. 1

Risk Assessment and Rationale

JAK inhibitors significantly increase the risk of herpes zoster infection in patients with immune-mediated inflammatory diseases:

• Studies show that certain JAK inhibitors (particularly peficitinib, baricitinib, and tofacitinib) are associated with higher rates of herpes zoster reactivation 1
• The American College of Rheumatology (ACR) guidelines recommend temporarily withholding JAK inhibitors (tsDMARDs) in children with pediatric rheumatic disease who develop symptomatic viral infections 2
• JAK inhibitors may dampen the innate antiviral response through inhibition of interferon signaling, potentially worsening host response to viral infections 2

Recommended Antiviral Prophylaxis

Primary Recommendations:

• Acyclovir: 15 mg/kg/day (divided doses) 3
• Valacyclovir: Alternative for patients who can swallow pills (improved bioavailability)

Duration of Prophylaxis:

• Continue prophylaxis for the duration of JAK inhibitor therapy
• Consider extending prophylaxis for 1-2 months after discontinuation of JAK inhibitors

Monitoring During Prophylaxis

• Regular clinical assessment for breakthrough viral infections
• CBC and LFTs within the first 1-2 months of JAK inhibitor usage and every 3-4 months thereafter 2
• Monitor for signs of herpes zoster reactivation despite prophylaxis

Special Considerations

VZV Serostatus:

• Consider checking VZV serostatus before initiating JAK inhibitor therapy
• For VZV-seronegative patients, consider VZV vaccination before starting JAK inhibitors if possible 2

Immunization Strategy:

• Inactivated vaccines are strongly recommended for children with JIA on immunosuppression 2
• Live attenuated vaccines (including varicella vaccine) are conditionally recommended against for children on immunosuppression 2
• Consider immunization for children with active non-systemic JIA who have not yet been immunized for varicella prior to starting immunosuppressive medications 2

Clinical Pearls and Pitfalls

• Important caveat: Low-dose acyclovir (15 mg/kg/day) has been shown to be effective for preventing VZV reactivation in pediatric HSCT patients 3, suggesting this dose may be sufficient for JAK inhibitor patients as well
• The risk of herpes zoster increases significantly after discontinuation of prophylaxis 3
• Antiviral prophylaxis should be considered for all pediatric patients on JAK inhibitors, not just those with a history of herpes zoster infection
• Avoid assuming that all JAK inhibitors carry equal risk; some (peficitinib, baricitinib, and upadacitinib at higher doses) appear to have greater association with herpes zoster reactivation 1

Approach to Breakthrough Infection

If breakthrough infection occurs despite prophylaxis:

1. Temporarily withhold JAK inhibitor therapy 2
2. Increase antiviral dose to treatment levels
3. Consider switching to IV acyclovir for severe cases
4. Resume JAK inhibitor only after resolution of infection
5. Consider higher prophylactic dose when restarting therapy

This approach aligns with the NCCN recommendation that once a patient has had HSV reactivation requiring treatment, they should receive HSV prophylaxis during all future episodes of immunosuppressive therapy 2.