JAK inhibitors pose increased risk of developing shingles

Exposure to the Janus kinase (JAK) inhibitors tofacitinib and upadacitinib, as well as to JAK inhibitors as a class, appears to put individuals at increased risk of developing herpes zoster infection, with the risk increasing at higher doses, as reported in a study.

Researchers conducted a systematic review and network meta-analysis to evaluate the risk of herpes zoster in relation to the use of biologics and small molecules for treating inflammatory bowel disease (IBD), including luminal Crohn’s disease and ulcerative colitis.

Multiple online databases were searched for relevant studies. The search yielded 25 trials involving a total of 9,935 patients for inclusion in the network meta-analysis. There were 72 cases of herpes zoster infection among 7,074 patients who received the active drug as opposed to only five cases among 2,861 patients who received placebo (1.02 percent vs 0.17 percent).

Obtained using a frequentist approach and a random effects model, pooled data revealed that the risk of herpes zoster infection was significantly high among patients who were on tofacitinib 10 mg twice a day (relative risk [RR], 6.90, 95 percent confidence interval [CI], 1.56–30.63; number needed to harm [NNH], 97, 95 percent CI, 19–1,022) and upadacitinib 45 mg once daily (RR, 7.89, 95 percent CI, 1.04–59.59; NNH, 83, 95 percent CI, 10–14,305) relative to those on placebo.

When drugs were assessed according to class, JAK inhibitors were most likely to increase the risk of infection as compared with placebo (RR, 4.78, 95 percent CI, 1.79–12.75; p=0.09; NNH, 151, 95 percent CI, 49–724). Of note, the risk increased with higher doses (lowest dose: RR, 3.16, 95 percent CI, 1.02–9.84; NNH, 265, 95 percent CI, 65–28,610; higher dose: RR, 5.91, 95 percent CI, 2.21–15.82; NNH, 117, 95 percent CI, 39–473).