Risk of Herpes Zoster and Postherpetic Neuralgia in Patients with Psoriasis Treated with Biologics: A nationwide study using target trial emulation framework

Patients with psoriasis have a higher baseline risk of herpes zoster (HZ) than the general population. This has raised concerns that TNF-α inhibitor use may be associated with an increased risk of HZ. However, the risk profiles for newer biologics, including IL-17 inhibitor (IL-17i), IL-12/23 inhibitor (IL-12/23i) and IL-23 inhibitor (IL-23i), remain uncertain. To compare HZ and postherpetic neuralgia (PHN) risks among different biologics, including ustekinumab, secukinumab, ixekizumab, guselkumab, etanercept and adalimumab, with traditional systemic treatments (TST). We conducted a retrospective cohort study by analyzing data from Taiwan's National Health Insurance Research Database (NHIRD 2011-2021). We included patients with psoriasis or psoriatic arthritis aged 20 years and above who had been treated with biologics or TST for at least six months. We classified patients by individual biologics or TST and followed them up for 2.5 years from drug initiation until the occurrence of outcome events or death. The primary outcome was the diagnosis of HZ. We used inverse probability of treatment weighting (IPTW) to adjust for covariates, including patient age, sex, comorbidities and co-medications. We used Cox proportional hazards models to evaluate the risk of HZ among different biologics. In total, we identified 815, 1870, 1095, 2327, 261, 303 and 98 patients with psoriasis receiving etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab and guselkumab, respectively. Compared to patients receiving TST, for those receiving ustekinumab and guselkumab the risk of HZ trended lower (weighted HR: 0.82, 95% CI: 0.61-1.11; 0.48, 0.22-1.02), while for those receiving adalimumab it was statistically significantly higher (weighted HR: 1.63, 95% CI: 1.22-2.18). Additionally, ustekinumab was associated with a reduced risk of PHN (HR: 0.22, 95% CI: 0.08-0.64). There were no significant differences in the risk of HZ between TST and either etanercept, secukinumab, ixekizumab or brodalumab. The findings suggested ustekinumab and guselkumab may be associated with a reduced risk of HZ and PHN, compared to TST. This study could have significance for real-world practice.