Study: Some Systemic Anti-Psoriasis Therapies Increase Risks of Herpes Zoster

New research from a Taiwanese insurance database suggests that some commonly used therapies against psoriasis may increase the risk of herpes zoster, although 2 other therapies lowered the risk.

Although biologic agents are frequently prescribed for patients with psoriasis, the resulting suppression of cell-mediated immunity can increase the risks of bacterial and viral infections, according to the research published in Scientific Reports. These potential links have been unproven, however, despite earlier study findings that patients with psoriasis face higher risks of herpes zoster infection.

To investigate this question, researchers identified 92,374 patients in the Taiwan National Health Insurance Research Database who were diagnosed with psoriasis between 2001 and 2013. They followed these patients for a median of 6.8 years and noted anti-psoriasis therapeutics as well as herpes zoster infection diagnoses.

According to their findings, etanercept, adalimumab, and methotrexate plus azathioprine were all associated with an increased risk of herpes zoster infection. The investigators also studied ustekinumab and found that none of these patients were diagnosed with herpes zoster. However, they said this could be because ustekinumab was not approved for use in Taiwan until 2011, so there was a limited amount of follow-up time for these patients.

In total, 5.2% of the patients were diagnosed with herpes zoster during the follow-up period. Older age, female sex, hypertension, dyslipidemia, psoriatic arthritis, and a high Charleston comorbidity index score were all associated with an increased risk of herpes zoster diagnosis. Concurrent exposures to steroids and statins were also linked with a higher risk.

“Similar to previous studies on general population or on diabetic patients, the use of statin is associated with higher risk of [herpes zoster],” the authors wrote. “The actual mechanisms of these associations have not [been] fully understood, but may involve the effect of statin on T cell function.”

Notably, however, the 3 anti-psoriasis therapies identified as increasing risk of herpes zoster were each associated with a more than quadrupled risk of infection. Etanercept had a hazard ratio of 4.78; adalimumab had a hazard ratio of 5.52; and methotrexate plus azathioprine had a hazard ratio of 4.17.

In addition to finding that methotrexate in combination with azathioprine increased the risk of herpes zoster, the researchers added that methotrexate combined with any biologic agent increased the risk, although not to a statistically significant level.

Two other treatments—phototherapy and acitretin—were associated with a lower risk of psoriasis, with hazard ratios of 0.76 and 0.39, respectively. The lower risk associated with acitretin could be attributable to the lower level of immunosuppression associated with this monotherapy. Similarly, the benefit associated with phototherapy could be caused by the increased level of vitamin D associated with UV exposure. Earlier research has suggested that vitamin D therapy could lower the risk of herpes zoster, the authors said.

“Although the effect of UV light on the skin is mainly anti-inflammatory, this may not imply an overt immunosuppressive effect,” the authors wrote. “Upon exposure to UV light, the human skin generates vitamin D, a vital nutrient for skeletal health and a well-known immunoregulator.”

Based on these findings, the investigators concluded that patients with moderate to severe psoriasis who are prescribed certain biologic agents may have a higher risk of herpes zoster infection. This risk should be considered, and other treatments may mitigate this risk while allowing for effective anti-psoriasis treatment.

REFERENCE

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. Scientific Reports. June 3, 2021. Accessed June 30, 2021. https://www.nature.com/articles/s41598-021-91356-3