Can Antibiotics Increase the Risk of Antidrug Antibodies to Infliximab?

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A lot of research is looking at how alterations in the microbiome affect a plethora of medical outcomes. Recently, there was a study linking sugar consumption in adolescence with an increased risk of adenomas (full text link: Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors; Gastroenterol 2021; 161: 128-142).

Now, a study indicates that taking oral antibiotics can influence the risk of developing antibodies to infliximab.

Full text (open access): 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 (thanks to John Pohl for this reference)

Citation: 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-IIRNGut Published Online First: 03 August 2021. doi: 10.1136/gutjnl-2021-325185

This study reviewed data from 1946 patients with 363 who developed anti-drug antibodies (ADA). Then, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days.

Key findings:

  • Cox proportional hazard model demonstrated an increased risk of ADA development in patients who used cephalosporins (HR=1.97, 95% CI 1.58 to 2.44), or penicillins with β-lactamase inhibitors (penicillin-BLI, HR=1.4, 95% CI 1.13 to 1.74), whereas a reduced risk was noted in patients treated with macrolides (HR=0.38, 95% CI 0.16 to 0.86) or fluoroquinolones (HR=0.20, 95% CI 0.12 to 0.35).
  • In mice exposed to infliximab, significantly increased ADA production was observed in cephalosporin as compared with macrolide pretreated mice. Germ-free mice produced no ADA.

My take: The combination of retrospective data and mouse studies suggests that taking some antibiotics (mainly penicillins and cephalosporins) could increase the risk of immunogenicity to infliximab and increase the risk of anti-drug antibodies.