Risk of Shingles with Mepolizumab vs Benralizumab
Both mepolizumab and benralizumab, as anti-IL-5 monoclonal antibodies, appear to carry an increased risk of herpes zoster compared to standard therapy, with emerging evidence suggesting this may be a class effect of anti-IL-5 biologics rather than a drug-specific phenomenon.
Evidence for Increased Herpes Zoster Risk
Class Effect of Anti-IL-5 Biologics
- Clinical trials have documented an association between mepolizumab and herpes zoster development 1
- A case report of disseminated herpes zoster following benralizumab initiation suggests a possible class effect of anti-IL-5 monoclonal antibodies, given the similar mechanism of action between these agents 1
- The 61-year-old patient in this case developed extensive disseminated herpes zoster after starting benralizumab, with initial vesicular lesions progressing from lumbar dermatomes to widespread body involvement 1
Comparative Safety Profile
- In systematic reviews of biologics for severe eosinophilic asthma, benralizumab, mepolizumab, and reslizumab all demonstrated slightly increased drug-related adverse events and serious adverse events, though the certainty of evidence was low to very low 2
- Both mepolizumab and benralizumab showed significant steroid-sparing effects in real-world studies of patients with severe asthma and EGPA, with a favorable overall tolerability profile, though specific herpes zoster rates were not separately quantified 3
Risk Mitigation Strategies
Vaccination Recommendations
- The recombinant zoster vaccine (Shingrix/RZV) should be administered to all patients ≥50 years before initiating anti-IL-5 biologics, ideally at least 4 weeks prior to starting immunosuppressive therapy 4
- For patients aged 18-49 years who will be starting immunosuppressive therapy, recombinant zoster vaccine is strongly recommended given the increased risk of herpes zoster with these biologics 4
- RZV is preferred over live zoster vaccine (Zostavax) because it can be safely administered to immunocompromised patients and has superior efficacy (91.3% vs 70%) 5
Screening and Prevention
- At diagnosis or before initiating biologic therapy, screen patients by history for varicella immunity (history of chickenpox, shingles, or two doses of varicella vaccine) 4
- Patients without clear history should be tested for VZV IgG 4
- Consider prophylactic antiviral therapy in patients with recurrent herpes zoster history who require anti-IL-5 biologic therapy 6
Clinical Management During Treatment
Monitoring and Early Intervention
- Maintain high clinical suspicion for herpes zoster in patients on mepolizumab or benralizumab, particularly in older adults and those with prior VZV reactivation 1, 7
- If herpes zoster develops during anti-IL-5 therapy, initiate antiviral treatment promptly with acyclovir or valacyclovir 4, 7
- For severe or disseminated cases, consider temporarily discontinuing the biologic until symptoms improve and all vesicles have crusted over 4
High-Risk Populations Requiring Extra Vigilance
- Older adults (≥60 years) have the highest absolute risk due to age-related decline in VZV-specific cellular immunity 4
- Patients with comorbidities including diabetes, rheumatoid arthritis, inflammatory bowel disease, or recent COVID-19 infection have additional risk factors beyond the biologic itself 4, 7
- Those on concurrent immunosuppression (corticosteroids, other immunomodulators) face compounded risk 4
Important Caveats
- The exact comparative incidence rates of herpes zoster between mepolizumab and benralizumab remain unclear, as head-to-head trials are lacking 2
- Most safety data comes from clinical trials with selected populations; real-world herpes zoster rates may differ 3
- The case report of disseminated herpes zoster with benralizumab represents severe disease, but the overall frequency of such severe presentations requires further study 1