Large-scale meta-analysis of infection risk with JAK-STAT inhibitors in 29,000 patients

Janus kinase signal transducer and transcription activator (JAK-STAT) inhibitors have revolutionized the treatment of immune-mediated inflammatory diseases (IMIDs) of the skin, such as in atopic dermatitis, alopecia areata and vitiligo. Although several meta-analyses have confirmed their efficacy, concerns remain about the risk of infection, as the JAK-STAT pathway plays a key role in immune defence. Previous meta-analyses examined only selected, pre-specified infection categories and have not comprehensively evaluated all reported infection types or compared systemic and topical agents.

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that reported infection-related adverse events in patients treated with systemic or topical JAK-STAT inhibitors for IMIDs of the skin. The study followed the PRISMA 2020 and Cochrane guidelines (PROSPERO: CRD 42024615839). Overall risk ratios (RRs) with 95% confidence intervals (CI) were calculated using a random-effects model.

Seventy-four RCTs were included, involving more than 29,000 patients. JAK-STAT inhibitors were associated with an increased risk of influenza (RR = 2.12, 95% CI 1.03-4.36), bronchitis (RR = 2.03, 95% CI 1.43-2.88) and herpes zoster (RR = 1.67, 95% CI 1.29-2.15) compared to a placebo. The risk was particularly elevated in patients with atopic dermatitis (influenza: 3.22, 95% CI 2.03-5.10, herpes zoster: RR = 2.00, 95% CI 1.34-2.99). No significant risks were identified for serious, fungal or opportunistic infections, and topical JAK-STAT inhibitors demonstrated a favourable safety profile comparable to vehicle controls.

This meta-analysis provides a comprehensive assessment of the risk of infection associated with JAK-STAT inhibitors in IMIDs of the skin. Although overall safety is acceptable, clinicians should be aware of the higher infection risk of influenza and herpes zoster and should consider vaccination and preventive strategies for high-risk patients with atopic dermatitis. The main limitation is that the included studies involved highly selected populations with few comorbidities and short follow-up.