Risk of herpes zoster and postherpetic neuralgia in patients with psoriasis treated with biologics: a nationwide study using a target trial emulation framework

BACKGROUND: Patients with psoriasis have a higher baseline risk of herpes zoster (HZ) than the general population. This has raised concerns that tumour necrosis factor (TNF)-α inhibitor use may be associated with an increased risk of HZ. However, the risk profiles for newer biologics, including interleukin (IL)-17, IL-12/23 and IL-23 inhibitors, remain uncertain. OBJECTIVES: To compare the risks of HZ and postherpetic neuralgia (PHN) in patients with psoriasis using different biologics (ustekinumab, secukinumab, ixekizumab, guselkumab, etanercept and adalimumab) vs. traditional systemic treatments (TSTs). METHODS: We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database (2011-2021). We included patients with psoriasis or psoriatic arthritis aged ≥ 20 years who had been treated with biologics or TSTs for at least 6 months. We classified patients by individual biologics or TST and followed them for up to 2.5 years from drug initiation until the occurrence of outcome events or death. The primary outcome was a diagnosis of HZ. We used inverse probability of treatment weighting to adjust for covariates, including patient age, sex, comorbidities and comedications. We used Cox proportional hazards models to evaluate the risk of HZ with different biologics. RESULTS: We identified 815, 1870, 1095, 2327, 261, 303 and 98 patients with psoriasis who were taking etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab and guselkumab, respectively. Compared with patients receiving TSTs, for those receiving ustekinumab and guselkumab the risk of HZ trended lower [ustekinumab: weighted hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.61-1.11; guselkumab: weighted HR 0.48, 95% CI 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 statistically significant differences in the risk of HZ between TSTs and either etanercept, secukinumab, ixekizumab or brodalumab. CONCLUSIONS: Our findings suggest that ustekinumab and guselkumab may be associated with a reduced risk of HZ and PHN vs. TSTs in patients with psoriasis. This study could have significance for real-world practice.