JAK Inhibitors Associated With Greatest Herpes Zoster Infection Risk in IBD

Janus kinase inhibitors are likely to increase the risk for herpes zoster infection in the treatment of patients with IBD.

Janus kinase (JAK) inhibitors increased risk for herpes zoster infection among those with inflammatory bowel disease (IBD), according to a systematic review and meta-analysis published in Alimentary Pharmacology & Therapeutics.

Researchers from the United Kingdom searched publication databases through October 2022 for randomized controlled trials (RCTs) that examined biological therapies for the treatment of IBD. The primary outcome of interest for this analysis was risk for herpes zoster infection. The final analysis included 22 articles reporting data from 25 RCTs and a pooled sample size of 9935.

The rate of herpes zoster infection was 1.02% among those who received active treatment compared with 0.17% among those who received placebo.

Risk for herpes zoster was highest for upadacitinib 15 mg daily (relative risk [RR], 13.09; 95% CI, 0.74-230.24), followed by upadacitinib 30 mg daily upadacitinib (RR, 12.58; 95% CI, 0.71-221.34), tofacitinib 10 mg twice daily (RR, 6.90; 95% CI, 1.56-30.63), and upadacitinib 45 mg daily (RR, 7.89; 95% CI, 1.04-59.59) compared with placebo.

In the dose-pooled analysis, only upadacitinib (RR, 9.19; 95% CI, 1.78-47.52) and tofacitinib (RR, 4.71; 95% CI, 1.06-20.82) were associated with herpes zoster infection risk compared with placebo.

The increased risk with janus kinase inhibitors was observed even in trials that used the lowest doses.

In the drug class-pooled analysis, JAK inhibitors alone were associated with increased herpes zoster infection risk compared with placebo (RR, 4.78; 95% CI, 1.79-12.75). Conversely, the drug class with the lowest herpes zoster infection risk was anti-interleukin (IL)-23 antibodies (RR, 0.66; 95% CI, 0.10-4.42).

In an analysis that considered dose and drug class, high-dose JAK inhibitors were associated with greater herpes zoster infection risk (RR, 5.91; 95% CI, 2.21-15.82) than low-dose JAK inhibitors (RR, 3.16; 95% CI, 1.02-9.84).

The findings from this analysis may have been biased as the trial designs were inherently different; however, there was overall low heterogeneity observed in the comparisons.

The researchers conclude, “The increased risk with janus kinase inhibitors was observed even in trials that used the lowest doses. […]National and international guidelines may need to take our findings into consideration and make recommendations concerning vaccination of patients with IBD prior to commencement of these therapies.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

This article originally appeared on Gastroenterology Advisor


Din S, Selinger CP, Black CJ, Ford AC. Systematic review with network meta-analysis: risk of herpes zoster with biological therapies and small molecules in inflammatory bowel disease. Aliment Pharmacol Ther. Published online December 31, 2022. doi:10.1111/apt.17379