S1609 Impact of Age on Anti-Drug Antibody Formation in Patients With Inflammatory Bowel Disease Treated With Tumor Necrosis Factor Inhibitors

Introduction: It is not known how the risk of immunogenicity to monoclonal antibodies that treat inflammatory bowel disease (IBD) changes with advancing age. Our study investigated whether older adults exhibit different rates of anti-drug antibody (ADA) formation to tumor necrosis factor (TNF) inhibitors. Methods: We conducted a single-center retrospective study in patients ages 18-89 seen between 2017-2024 with a diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) receiving anti-TNF medication. Multiple logistic regression was used to evaluate independent associations between clinically relevant ADA (crADA), defined as positive ADA with concurrent free serum drug level below threshold levels (adalimumab <7.5 ug/mL, infliximab <5 ug/mL, certolizumab <20 ug/mL, golimumab <2 ug/mL), and age, anti-TNF dosing, history of autoimmune disease, current or prior smoking history, IBD type (UC or CD), and concomitant immunomodulator (methotrexate or thiopurine) use. Results: We identified 925 patients who underwent 1,509 ADA tests. Of these, 969 tests had associated drug dosing information and were included in the final analysis. Ninety-one ADA tests were performed on 68 older adults (ages 60-89 y), and 878 tests were performed on 587 younger adults (ages 18-59 y). Older adults undergoing ADA testing were more likely to be current or prior smokers (49% vs 26%, P < 0.01) compared to younger adults. Twenty-four percent of tests in older adults showed crADA compared with 20% in younger adults (P = 0.33). In multivariate analysis, being an older adult was not associated with crADA formation (OR 1.45, 95% CI 0.85-2.45), nor was age when analyzed as a continuous variable (OR 1.01, 95% CI 0.99-1.02). Escalated anti-TNF dosing was associated with decreased rate of crADA (OR 0.43, 95% CI 0.31-0.60). Other factors such as autoimmune disease (OR 1.44, 95% CI 0.91-2.29), smoking history (OR 0.81, 95% CI 0.56-1.18), and diagnosis of CD (OR 1.39, 95% CI 0.92-2.09) were not associated with crADA formation. When escalated drug dosing was added to the model, concomitant immunomodulator use was also not independently associated with crADA formation (OR 0.8, 95% CI 0.57-1.12). Conclusion: Older adults with IBD demonstrated similar rates of crADA formation to anti-TNF compared to younger adults, indicating chronological age alone does not influence ADA development. Decisions regarding ADA prevention and management should be guided by clinical context rather than chronological age.