RT Journal Article
SR Electronic
T1 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
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 287
OP 295
DO 10.1136/gutjnl-2021-325185
VO 71
IS 2
A1 Yuri Gorelik
A1 Shay Freilich
A1 Shiran Gerassy-Vainberg
A1 Sigal Pressman
A1 Chagit Friss
A1 Alexandera Blatt
A1 Gili Focht
A1 Yiska Loewenberg Weisband
A1 Shira Greenfeld
A1 Revital Kariv
A1 Nathan Lederman
A1 Iris Dotan
A1 Naama Geva-Zatorsky
A1 Shai Shlomo Shen-Orr
A1 Yechezkel Kashi
A1 Yehuda Chowers
A1 ,
YR 2022
UL http://gut.bmj.com/content/71/2/287.abstract
AB Objective Anti-drug antibodies (ADA) to anti-tumour necrosis factor (anti-TNF) therapy drive treatment loss of response. An association between intestinal microbial composition and response to anti-TNF therapy was noted. We therefore aimed to assess the implications of antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD).Design We analysed data from the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all patients with IBD in Israel. We included all patients treated with anti-TNF who had available ADA levels. Survival analysis with drug use as time varying covariates were used to assess the association between antibiotic use and ADA development. Next, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days.Results Among 1946 eligible patients, with a median follow-up of 651 days from initiation of therapy, 363 had positive ADA. 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.Conclusion ADA production is associated with the microbial composition. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillin-BLIs, or by treatment with fluoroquinolones or macrolides.Data are available upon reasonable request. The data used in the study was obtained from the epi-IIRN registry.