Association of Antibiotic Use with Durability of Biologic Agents in Inflammatory Bowel Disease: a report from the epi-IIRN.

Abstract

Different antibiotic classes were reported to have variable effects on immunogenicity towards anti-TNF agents. However, the impact of antibiotic administration on biologic treatment durability was not investigated. We aimed to assess the association between antibiotic treatment and persistence of different classes of biologic therapy in inflammatory bowel disease (IBD) patients. Data from the epi-IIRN, a nationwide registry of all Israeli IBD patients was analyzed. All patients who filled a prescription of either infliximab, adalimumab, vedolizumab, or ustekinumab, were included. Treatment cessation was defined as drug discontinuation of at least 6 months. Macrolides, cephalosporins, fluoroquinolones and penicillins with beta-lacatamase inhibitors were selected as primary exposure variables. Survival analysis was performed using marginal structural models for each drug separately. 13,513 IBD patients with a total of 39,600 patient years were included. Significant differences of overall treatment persistence were demonstrated, with highest persistence rates for ustekinumab and the lowest for infliximab treatment. Macrolides were found to be significantly associated with reduced risk of infliximab cessation (aHR 0.72, 95% CI 0.62-0.89). Flouroquinolones and cephalosporins were associated with an elevated risk of adalimumab treatment cessation (aHR 1.33, 95% CI 1.22-1.46; and aHR 1.20, 95% CI 1.08-1.34, respectively). No significant effects of the studied antibiotics were observed in ustekinumab and vedolizumab users. Specific antibiotic classes are associated with duration of anti-TNF treatment, but not with durability of vedolizumab, or ustekinumab treatments. Further research is required to study the effect of specific antibiotics on response to biologics.