Shahzad I Mian, Jiyu Kim, Andrea B Troxel, Elisabeth J Cohen, Bennie H Jeng, ZEDS Trial Research Group
Participants who received suppressive valacyclovir treatment compared with placebo had a significantly lower likelihood of new or worsening ocular adverse events at 18 months; the effect of valacyclovir was similar regardless of administration of RZV.
PURPOSE: Although the recombinant zoster vaccine (RZV) has demonstrated high efficacy in prevention of herpes zoster, there are concerns about its safety in patients with herpes zoster ophthalmicus with no clear evidence regarding the benefit of combining RZV with suppressive antiviral therapy. This secondary analysis of the Zoster Eye Disease Study outcomes by RZV vaccination status aims to assess potential benefit and risk of vaccination.
METHODS: The Zoster Eye Disease Study was conducted at 95 sites from November 2017 to June 2024. RZV administration, both before and after enrollment, was recorded on electronic data entry forms. Five hundred twenty-seven participants were randomized to receive 12 months of double-masked daily valacyclovir 1000 mg or placebo and then followed for 18 months. In this analysis, we evaluated the impact on study outcomes within 3 months of RZV vaccination and at 12 and 18 months.
RESULTS: Of the 527 participants, 122 (23.1%) received RZV, 37 (7.0%) pre-enrollment (15 on valacyclovir and 22 on placebo), and 85 (16.1%) postenrollment (41 on valacyclovir and 44 on placebo). Among participants who received RZV after enrollment, end points occurred within 3 months after the first shot in 5/85 (5.9%), including 0 (0/41, 0%) on valacyclovir and 5 (5/44, 11.4%) on placebo (P = 0.057), after the second shot in 2/50 (4.0%), including 2 (2/26, 7.7%) on valacyclovir and 0 on placebo (P = 0.491). Over the first 12 months, the time-dependent Cox regression analysis estimated a hazard ratio of 0.726 for end points comparing those with RZV vaccination with those without [95% confidence interval (CI) 0.39-1.34, P = 0.303]. Over 18 months, the HR comparing valacyclovir without RZV with placebo was 0.75 (95% CI 0.56-0.99, P = 0.046), and comparing valacyclovir with RZV with placebo was 0.51 (95% CI 0.27-0.98, P = 0.042).
CONCLUSIONS: Participants who received suppressive valacyclovir treatment compared with placebo had a significantly lower likelihood of new or worsening ocular adverse events at 18 months; the effect of valacyclovir was similar regardless of administration of RZV.