Systematic review with network meta‐analysis: Risk of Herpes zoster with biological therapies and small molecules in inflammatory bowel disease

Summary Background Biologics and small molecules for inflammatory bowel disease (IBD) may increase infection risk. Herpes zoster causes acute and long‐term symptoms, but vaccination is not recommended in patients with IBD, unless >50 years of age. Aims To examine risk of Herpes zoster infection with all licensed biologics and small molecules for IBD using network meta‐analysis. Methods We searched the literature to 4th October 2022, for randomised controlled trials of these drugs in luminal Crohn's disease or ulcerative colitis reporting data on occurrence of Herpes zoster infection during follow‐up. We used a frequentist approach and a random effects model, pooling data as relative risks (RRs) with 95% confidence intervals (CIs). Results We identified 25 trials (9935 patients). Only tofacitinib 10 mg b.d. (RR = 6.90; 95% CI 1.56–30.63, number needed to harm (NNH) = 97; 95% CI 19–1022) and upadacitinib 45 mg o.d. (RR = 7.89; 95% CI 1.04–59.59, NNH = 83; 95% CI 10–14,305) were significantly more likely to increase risk of Herpes zoster infection. Janus kinase inhibitors were the most likely drug class to increase risk of infection, and risk increased with higher doses (RR with lowest dose = 3.16; 95% CI 1.02–9.84, NNH = 265; 95% CI 65–28,610, RR with higher dose = 5.91; 95% CI 2.21–15.82, NNH = 117; 95% CI 39–473). Conclusions In a network meta‐analysis, the janus kinase inhibitor tofacitinib, and all janus kinase inhibitors considered as a class, were most likely to increase risk of Herpes zoster infection. Risk increased with higher doses.