Effectiveness of Amenamevir Vs. Valacyclovir in Preventing Herpes Zoster‐Related Hospitalization and Complications: A Target Trial Emulation Using a Large Japanese Claims Database

Amenamevir is a novel anti-herpes zoster drug that is increasingly used in Japan because of its once-daily administration and lack of renal dose adjustment requirements. However, evidence of its clinical effectiveness is limited. This study aimed to estimate the clinical effectiveness of amenamevir vs. valacyclovir in preventing zoster-related hospitalizations and complications. Using a nationally representative claims database from 2017 to 2024, we conducted a retrospective cohort study with a new-user, active-comparator design. We included adults (aged ≥ 18 years) with uncomplicated herpes zoster who initiated amenamevir or valacyclovir treatment. Propensity score overlap weighting was used to adjust for differences between patients prescribed amenamevir and valacyclovir. The primary outcome was 30-day zoster-related hospitalization. The secondary outcomes included diagnoses of zoster-related complications (zoster encephalitis, zoster meningitis, disseminated zoster, and zoster ocular disease) and acute kidney injury. In total, 67 912 individuals (38.2% male; mean age, 70.1 years) were included. After overlap weighting, baseline covariates were well-balanced between the groups. The risk of 30-day zoster-related hospitalization was similar between amenamevir and valacyclovir users (0.73% vs. 0.73%; risk ratio [RR], 1.00; 95% confidence interval [CI], 0.84-1.20). For secondary outcomes, zoster encephalitis (0.02% vs. 0.01%; RR, 2.09; 95% CI, 0.62-7.10), zoster meningitis (0.04% vs. 0.02%; RR, 2.32; 95% CI, 0.89-6.09), and disseminated zoster (0.13% vs. 0.10%; RR, 1.25; 95% CI, 0.79-1.97) did not differ significantly between the groups. However, amenamevir was associated with a higher risk of zoster ocular disease (0.84% vs. 0.67%; RR, 1.25; 95% CI, 1.05-1.49) and a lower risk of acute kidney injury (0.02% vs. 0.09%; RR, 0.23; 95% CI, 0.10-0.53). Based on our findings, amenamevir may be a useful option for herpes zoster, particularly in clinical settings where timely assessment of renal function is not available. However, caution is warranted regarding possible increases in ocular complications.