Systemic Therapies Linked With Herpes Zoster Risk in Patients With Psoriasis

Three biologics appeared to increase herpes zoster risk, but 2 other therapies were shown to lower the risk, according to a study of patients in a Taiwanese national database.

A new report shows certain systemic therapies for the treatment of psoriasis can increase a patient’s risk of herpes zoster (HZ) infection.

Etanercept (Enbrel), adalimumab (Humira), and methotrexate plus azathioprine all appeared to be associated with a heightened risk of HZ infection, according to data published in Scientific Reports.

Corresponding author George Kuo, PhD, of the Linkou Chang Gung Memorial Hospital, in Taiwan, and colleagues, explained that it has previously been shown that patients with psoriasis face a higher risk of HZ infection.

“However, the association between HZ risk and different systemic therapies, especially biologic agents, remains controversial,” they wrote.

Biologic agents can be highly effective at treating psoriasis, but they also result in suppression of cell-mediated immunity, raising the risk that they increase risk of bacterial and viral infections.

Kuo and colleagues sought to understand the risk on a therapy-by-therapy basis. To do so, they identified 92,374 patients in the Taiwan National Health Insurance Research Database who were newly diagnosed with psoriasis between 2001 and 2013. The investigators tracked these patients for a median of 6.8 years, noting the use of anti-psoriasis therapies and looking for diagnoses of HZ infection.

In all, 4834 patients (5.2%) were diagnosed with HZ. The authors found that older age, female sex, hypertension, dyslipidemia, psoriatic arthritis, and a relatively high Charleston comorbidity index score were all associated with increased risk of HZ infection. Concurrent exposure to steroids and statins was also linked with an increased risk. However, the 3 therapies identified as increasing HZ risk each more than quadrupled the risk of infection: etanercept (HR, 4.78; 95% CI, 1.51–15.17); adalimumab (HR, 5.52; 95% CI, 1.72–17.71); and methotrexate plus azathioprine (HR, 4.17; 95% CI, 1.78–9.82).

Kuo and colleagues said this is the first report to link etanercept and adalimumab to HZ infection. In addition to finding that methotrexate plus azathioprine significantly increased the risk, they also found that methotrexate combined with any biologic agent increased risk, though not to a statistically significant level.

Another biologic, ustekinumab (Stelara) was also studied, and none of those patients became infected with HZ. However, Kuo and colleagues said that could be due to the fact that it was not approved in Taiwan until 2011, and therefore there was a limited amount of follow-up time for those patients in the study.

Conversely, 2 psoriasis treatments—phototherapy and acitretin (Soriatane)—were associated with a lower risk of psoriasis. Phototherapy had a HR of 0.76 (95% CI, 0.60–0.96) and acitretin had a HR of 0.39 (95% CI, 0.24–0.64). Kuo and colleagues said the lower risk associated with acitretin may be due to the lower level of immunosuppression associated with acitretin monotherapy. In the case of phototherapy, which uses UV light, they suggested that the benefit is linked with the increased level of vitamin D associated with UV exposure. Earlier reporting has suggested that vitamin D therapy can lower the risk of HZ.

The authors noted limitations including the unavailability of several other biologics at the time of the study, and a lack of data related to psoriasis severity, which limited their ability to adjust their findings based on severity or laboratory results. However, they noted that in previous studies, the use of systemic therapies or a psoriatic arthritis diagnosis have been used as proxies for labeling cases “moderate to severe,” suggesting that the patients in this study could be assumed to be in the same category.


Ting SW, Ting SY, Lin YS, Lin MS, Kuo G. Risk of herpes zoster in psoriasis patients receiving systemic therapies: a nationwide population-based cohort study. Sci Rep. Published online June 3, 2021. doi:10.1038/s41598-021-91356-3

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