Risk of infections during treatment with oral Janus kinase inhibitors in randomized placebo-controlled trials: A systematic review and meta-analysis

Janus kinase (JAK) inhibitors block pathways involved in inflammation and immune response, making JAK inhibitors useful in the treatment of various diseases. While the efficacy of these drugs has been proven in several studies, their safety profile needs to be further investigated. In this systematic review and meta-analysis, we examined the risk of infections during treatment with oral JAK inhibitors with no concomitant treatment compared to placebo in phase 2 and 3 randomized, placebo-controlled trials. The medical databases PubMed, Web of Science, and EMBASE were searched from inception through February 2024, yielding 13,567 nonduplicate articles, of which 69 were included in the final quantitative analysis. Overall, we found that treatment with oral JAK inhibitors was associated with an increased risk of infections compared to placebo across all indications (relative risk: 1.39 [95% CI: 1.096-1.76, P = .0067]) and in dermatologic indications (relative risk: 1.46 [95% CI, 1.10-1.93, P = .0097]). Remarkably, an increased risk of herpes zoster infections was found in dermatologic indications but not in nondermatologic indications. In conclusion, we identified a significantly increased risk of developing infections during treatment with oral JAK inhibitors compared to placebo across indications. In sub-analyses, we additionally found an increased risk of herpes zoster in dermatologic indications.