Incidence of Anti-Drug Antibody Development in Older Adults with Inflammatory Bowel Disease Treated with Tumor Necrosis Factor Alpha Inhibitors: A Large Multicenter Cohort Study

Abstract Background It has been theorized that age related immunosenescence reduces the risk of developing anti-drug antibodies (ADAs). This has significant implications regarding choice of therapy and need for routine drug monitoring in this group. We investigated the incidence of ADAs in older adults compared to younger adults with inflammatory bowel disease (IBD). Methods We conducted a multicenter retrospective cohort study including all older adults (ages ≥60 years) with IBD treated with a tumor necrosis factor inhibitors (TNFi); adults ages 18-59 years old were included in a 4:1 ratio. Kaplan-Meier and Cox regression methods compared longitudinal risk of ADA development between groups. Multivariable models evaluated the association of potential risk factors with ADA development. Results 182 (19.7%) older adults and 738 (80.2%) younger adults were included in the study. The risk of ADAs was higher in older adults compared to younger adults (adjusted hazard ratio [aHR] 2.20; 95% confidence interval [CI] 1.44-3.36). Proactive therapeutic drug monitoring (TDM) was inversely associated with ADA development (aHR 0.36; 95% CI 0.25-0.52). Conclusion Older adults are more likely to develop ADAs against TNFi compared to younger adults. Proactive TDM may be considered in this population for early identification of ADAs and subtherapeutic trough levels, enabling timely dose escalation or treatment modification.