Introduction

Upadacitinib is a novel selective Janus kinase 1 (JAK1) inhibitor. However, it increases the risk of herpes zoster infection.

Aim

We aimed to estimate the short-term risk and long-term incidence rate of herpes zoster in patients with atopic dermatitis (AD) and psoriatic arthritis (PsA) treated with different doses of upadacitinib.

Methods

Randomised controlled trials and long-term (≥ 52 weeks) open-label extension studies of upadacitinib for AD and PsA were included. Short-term odds ratios (ORs) and long-term exposure-adjusted event rates (EAERs) for herpes zoster infection were estimated using R software 4.4.3 and STATA 18.0.

Results

This review included 8 randomised controlled studies and 11 open-label extension studies. The short-term analysis showed that in AD patients, the ORs for herpes zoster infection after 15 mg and 30 mg upadacitinib were 2.62 (95% CI: 1.06–6.47) and 3.13 (95% CI: 1.38–7.12), respectively. In PsA patients, the ORs were 1.39
(95% CI: 0.45–4.33) and 2.43 (95% CI: 0.96–6.16), respectively. The long-term analysis showed that the EAER for herpes zoster infection in AD and PsA patients using 15 mg upadacitinib was 1 year: 3.87/100 patient-years (PYs), 2 years: 4.68/100 PYs, and 3 years: 4.30/100 PYs; for 30 mg, the EAER was 1 year: 6.96/100 PYs, 2 years: 8.29/100 PYs, and 3 years: 7.53/100 PYs. Upadacitinib 30 mg was associated with a significantly higher risk of herpes zoster compared with 15 mg, with consistent dose-dependent effects at 1-year (OR = 1.78, 95% CI: 1.41–2.24), 2-year (OR = 1.80, 95% CI: 1.28–2.53), and 3-year follow-up (OR = 1.94, 95% CI: 1.59–2.35).

Conclusions

Upadacitinib increases the risk of herpes zoster in AD and PsA patients, with a more significant effect in AD patients and a dose-dependent relationship over time.