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

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.