Antibiotics & anti-TNFs

September 15, 2021

Issue 17

Clinical Question

Does antibiotic use affect response to anti-TNF agents?

Editor’s Bottom Line

These data suggest an association between antibiotic exposure and sensitization to anti-TNF monoclonal antibodies. Although this relationship is intriguing, it may not be truly causal. More data are needed.  

Reference

Gorelik Y, Freilich S, Gerassy-Vainberg S, et al. Antibiotic use differentially affects the risk of anti-drug antibody formation during anti-TNFα therapy in inflammatory bowel disease patients: a report from the epi-IIRN. Gut. Epub ahead of print August 12, 2021; http://dx.doi.org/10.1136/gutjnl-2021-325185

Synopsis

In light of prior evidence indicating that the composition of the intestinal microbiome can affect response to anti-tumor necrosis factor (TNF) treatment, researchers in Israel set out to examine whether antibiotics can impact anti-TNF response. They specifically looked at the development of anti-drug-antibodies (ADA) in 1,946 patients with IBD who had received infliximab or adalimumab. The patients were enrolled in a nationwide IBD registry and had ADA titres available.

Over a median follow-up of 651 days after anti-TNF treatment initiation, 18.6% of patients developed ADAs. In a multivariate analysis controlling for a host of potential confounding variables, use of cephalosporins (Hazard Ratio [HR] = 1.97; 95% Confidence Interval [CI], 1.58–2.44) or penicillins with beta-lactamase inhibitors (HR = 1.4; 95% CI, 1.13–1.74) during the three years prior to anti-TNF initiation was linked to a higher likelihood of having ADAs. Moreover, prior administration of both cephalosporins and penicillins with beta-lactamase inhibitors was associated with a higher likelihood of ADA than use of either class of agents alone.

In contrast, patients who had received a macrolide (HR = 0.36; 95% CI, 0.16–0.82), a fluoroquinolone (HR = 0.20; 95% CI, 0.12–0.35) or, to a lesser extent, penicillin (HR = 0.79; 95% CI, 0.64–0.98), were less likely to develop ADAs than those who had not received these agents. 

In another part of the study, the investigators administered a cephalosporin or a macrolide in mouse models and subsequently exposed them infliximab. They found that ADA levels were significantly higher in mice given a cephalosporin, compared to macrolide-treated mice. Neither antibiotic affected ADA levels in germ-free mice.

Details

Study Design: Retrospective cohort analysis

Funding: Leona M. and Harry B. Helmsley Charitable Trust and Israeli Ministry of Science and Technology

Allocation: None

Setting: Multicenter

Level of Evidence: 2b