Baricitinib Increases Herpes Simplex Risk in Patients with AD

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The new analysis suggests the infections rarely leads to discontinuation in patients with atopic dermatitis.

Treatment-emergent herpes simplex infection is common among patients with atopic dermatitis (AD) who are treated with baricitinib (Olumiant), but cases of eczema herpeticum and herpes zoster are not common, according to new research.

Even when patients became infected, however, cases tended to be mild or moderate and usually did not lead to discontinuation of the medication.

Previous research has indicated that patients with AD are at a higher risk of bacterial and viral infections, in part because they have reduced levels of interferon-γ and its receptor and express receptor variants, explained corresponding author Andreas Wollenberg, MD, of Ludwig Maximillian University of Munich, and colleagues.

The reduction is particularly notable in patients with a history of eczema herpeticum, the authors noted. Since interferons are mediated through the Janus kinase 1 and 2 (JAK1 and JAK2) pathways, and baricitinib is a JAK1/JAK2 inhibitor, Wollenberg and colleagues said cases of eczema herpeticum are of particular interest in patients with AD who receive baricitinib.

Baricitinib has been associated with increased rates of treatment-emergent herpes zoster infection in patients being treated for rheumatoid arthritis, the investigators noted, but the primary evidence available for AD is limited.

The authors said there remains a need for a better understanding of barictinib’s disease-specific safety profile and characteristics in patients with AD.

Wollenberg and colleagues reviewed 6 double-blinded, placebo-controlled trials, and 2 long-term extension studies of baricitinib in patients with AD in order to determine how commonly patients experienced treatment-emergent herpes simplex infections, including eczema herpeticum and herpes zoster. All of the patients in the studies were adults, and all received at least 1 dose of the drug.

In all, 2,351 patients representing 2,247 person-years were included in the analysis. Herpes simplex infections were reported in 8.9% of patients, but 93.3% of those cases were characterized as mild or moderate.

Patients permanently discontinued the therapy in just 2.2% of cases. Treatment-emergent eczema herpeticum, meanwhile, was reported in just 1.7% of patients. Again, most cases (79.1%) were considered mild or moderate, and three-quarters of cases (74.2%) were one-time events.

That rate was lower than in previous reports, but the authors noted a significant caveat: the clinical trial protocols called for patients with a history of eczema herpeticum to be excluded from the trial, “which may explain the lower frequency,” the authors said.

Finally, 2.1% of patients experienced treatment-emergent herpes zoster infections, but there was no dose-dependent relationship. The investigators noted treatment-emergent herpes zoster infections were less frequent in patients who received 4-mg doses of baricitinib than in patients receiving a lower dose.

The frequency of infections did not increase with prolonged exposure to the drug, and no serious adverse events of herpes zoster were reported.

Overall, the data as a whole suggested patients with AD who wee treated with baricitinib faced an increased risk of herpes simplex infections, but those cases are generally uncomplicated.

“These events were mostly mild-to-moderate, presented as localized oral/perioral herpes simplex, and rarely led to discontinuation,” the team concluded.

The study, "An integrated analysis of herpes virus infections from eight randomised clinical studies of baricitinib in adults with moderate to severe atopic dermatitis," was published online in JEADV.