JAK inhibitors more than double patients’ risk of contracting influenza and herpes zoster compared with placebo, though they carry no elevated risk of serious infections, a large meta-analysis has found.

Hungarian dermatologists reviewed 74 randomised controlled trials involving 29,000 patients where JAK-STAT inhibitors were tested against placebo. They found:

• Patients receiving JAKis were more than twice as likely to develop influenza or bronchitis
• Patients were 67% more likely to develop herpes zoster infection
• Patients with atopic dermatitis faced three times the flu risk and double the herpes zoster risk compared with placebo

No significant increase in risk was identified for serious, fungal or opportunistic infections.

The authors also found no association between JAK inhibitors and COVID-19, though they cautioned this finding should be interpreted carefully, given JAK-STAT inhibitors had been investigated as treatments for COVID-19-related cytokine storms and may continue to influence antiviral defences during chronic use.

Writing in the Journal of the European Academy of Dermatology and Venereology [link here], the authors said this was the first meta-analysis to show an increased influenza risk in patients treated with JAK-STAT inhibitors compared with placebo in inflammatory skin diseases, and that the identification of increased oral herpes risk added to growing evidence of class-specific viral susceptibility.

Atopic dermatitis was already associated with heightened susceptibility to skin and systemic infections, they noted, and JAKi treatment may further impair antiviral immune response.

The overall infection rates within the studies were low, and the safety profiles of the JAKis studied supported their use across a range of dermatological conditions, the authors said.

The findings were supported by the prospective BioDay registry, which showed patients with moderate-to-severe atopic dermatitis on JAK inhibitors had higher infection rates, particularly herpes infections.

Together, the data reinforced the importance of herpes zoster and influenza vaccination before initiating JAK-STAT inhibitor therapy, the authors said, particularly in adults aged 50 and over and immunocompromised patients with atopic dermatitis, in line with American Academy of Dermatology guidelines.