Risk of Herpes Zoster with Nucala (Mepolizumab)
Herpes zoster has occurred in patients receiving Nucala, with the FDA label explicitly warning about this opportunistic infection and recommending consideration of vaccination if medically appropriate. 1
Quantified Risk from Clinical Trials
The FDA-approved prescribing information provides specific incidence data from controlled trials:
In 24-week trials: 2 patients receiving Nucala 100 mg subcutaneous (n=263) developed herpes zoster versus 0 patients receiving placebo (n=257), making herpes zoster the only serious adverse event occurring in more than 1 patient at higher rates than placebo 1
In 52-week trials: 3 cases of herpes zoster occurred in patients receiving mepolizumab 75 mg IV (n=153) compared with 2 patients in the placebo group (n=155) 1
Long-term extension studies: Additional cases of herpes zoster were reported among 998 patients receiving Nucala 100 mg in ongoing open-label studies, though the overall adverse event profile remained similar to the initial trials 1
Clinical Context and Mechanism
The increased herpes zoster risk with Nucala occurs because:
Mepolizumab is an anti-IL-5 monoclonal antibody that depletes eosinophils, which may play a role in immune surveillance against varicella zoster virus reactivation 1
Herpes zoster results from reactivation of latent varicella zoster virus in dorsal root ganglia, which occurs when cell-mediated immunity declines with aging or immunosuppression 2, 3, 4
Approximately 20-30% of people develop herpes zoster over their lifetime, with incidence increasing markedly after age 50 years due to natural decline in VZV-specific cell-mediated immunity 2
Prevention Strategy: Vaccination Recommendations
The FDA label specifically states to "consider vaccination if medically appropriate" for patients receiving Nucala. 1
For Immunocompetent Adults ≥50 Years
Administer Shingrix (recombinant zoster vaccine) as a 2-dose series with the second dose given 2-6 months after the first dose, ideally before initiating Nucala therapy 5
Shingrix demonstrates >90% efficacy across all age groups ≥50 years with protection sustained for at least 8-10 years 5
Never use live-attenuated Zostavax in patients on or about to start immunosuppressive therapy like Nucala, as live vaccines are contraindicated in immunocompromised patients 2, 5
For Immunocompromised Adults 18-49 Years
Shingrix is recommended for adults aged ≥18 years who are or will be immunocompromised, including those on biologics like Nucala 5
Consider a shorter schedule with the second dose given 1-2 months after the first dose for immunocompromised patients 5
Optimal Timing
Complete the full 2-dose Shingrix series before starting Nucala whenever possible to maximize immune response while the patient is not yet immunosuppressed 6
If urgent Nucala initiation is required, administer at least the first Shingrix dose before starting therapy, with the second dose completed after Nucala has been started (though immune response may be somewhat reduced) 6
Shingrix should be administered ≥4 weeks before beginning highly immunosuppressive therapy when possible 2
Important Clinical Caveats
Do not delay or discontinue Nucala therapy solely due to herpes zoster risk - the benefits of asthma control typically outweigh this manageable risk, especially with appropriate vaccination 1
Patients who develop herpes zoster while on Nucala should receive prompt antiviral treatment (acyclovir, valacyclovir, or famciclovir) within 72 hours of rash onset to decrease severity and duration of acute pain and reduce risk of postherpetic neuralgia 3, 4
Vaccination after a herpes zoster episode is still recommended once acute symptoms resolve (typically waiting at least 2 months), as prior infection does not provide reliable protection against recurrence 5
The majority of adults (88-91%) have been exposed to varicella zoster virus even without recalled chickenpox history, making them capable of developing shingles 5