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JAK inhibitors increased the risk of herpes zoster (HZ) and upper respiratory tract (URT) infections in patients with atopic dermatitis (AD). On subsequent analysis, however, that increase diminished when evaluating individual agents.

That's according to the results of a systematic review and meta-analysis published in the .

After analyzing results from 11 separate studies, investigators concluded that JAK inhibitors increased the risk of HZ and URT infections in patient participants compared with placebo (OR 2.22, 95% CI 1.30-3.77). That increase, however, was mitigated in subgroup analysis of individual drugs. There was no significant increase in serious risk infection among JAK inhibitor recipients (OR 0.79, 95% CI 0.53-1.19).

Jensen Yeung, MD, a dermatologist-researcher with the University of Toronto in Canada, discussed the review with the Reading Room. The exchange has been edited for length and clarity.

What prompted your investigation?

Yeung: JAK inhibitors have become a very popular choice in the treatment paradigm of AD. But in counseling patients who are about to start JAK inhibitor therapy, we have to discuss potential side effects associated with these agents.

One of my patients asked me how much the risk of infection increased if she took the agent we recommended. She made a good point that the package insert lists many different side effects, including infection. She was not alone. A number of patients also raised this issue. Their questions initiated our deep dive into infection risk with JAK inhibitors.

We examined randomized controlled trials with JAK inhibitors in AD.

What were your key findings?

Yeung: We looked at several outcomes. The first was increased risk of HZ. The second was URT infection risk. A third was the number of serious infections.

The overall risk of HZ from JAK inhibitors was elevated compared to placebo. But in sub-group analyses of individual JAKs, there was no significant increase compared to placebo. The same was true for URT infections.

Moreover, there was no significant increase in the risk of serious infections as a whole or in sub-analyses with individual agents.

Did anything surprise you about the analysis or the findings?

Yeung: It was quite interesting to see an increased risk of HZ and URT infection overall, but not in sub-analyses. It was also interesting to find no increased risk of serious infections.

What might dermatologists take away from your study?

Yeung: Ultimately, I think these findings are pretty reassuring.

We still have to treat these patients in real life, however. One could argue that patients who enroll in trials are different from those we see in real-world practice. For example, in clinical trials, often patients might not be able to use a topical agent along with the systemic treatment being studied. I'd like to examine such questions using real-world evidence.