Older Adults Are at Higher Risk for Developing Anti-TNF Antibodies

Introduction: As the inflammatory bowel disease (IBD) patient population ages, there will be an increasing number of individuals requiring advanced therapies. Although older age is thought to be associated with immunosenescence, there are data suggesting that older adults may be at higher risk for antibody development as the result of biologic use. Methods: Using a large commercial laboratory database (Prometheus Laboratories), we extracted infliximab (IFX) dosing as well as antibody to infliximab (ATI) levels for all individuals using this assay from 2015-2021. Our primary outcome was the presence of ATI (titer >3.1 U/mL). Frequencies were recorded as categorical variables with chi-square analysis used, and multivariable logistic regression was employed to assess the impact of IFX dose, age (< 60 years-old v. ≥60 years-old), and IBD subtype on the development of ATI. Results: Overall, there were 22,197 unique specimens, with 3,028 (13.6%) having ATI. When stratified by age, individuals ≥60 years-old developed ATI 18.1% (473/2,612) of the time as compared to 15.0% (2,555/17,030) for individuals < 60 years of age (p< 0.01, Figure). Among all individuals with IFX dose < 10mg q8 weeks, older adults (≥60 years of age) were more likely to develop ATI as compared to younger adults (22.8% vs. 16.2%, respectively, p< 0.01); however, when IFX dose was ≥10mg/kg q8 weeks, age ≥ 60 years-old was no longer significantly associated with the development of ATI (9.9% if < 60 years-old vs. 10.6% if ≥60 years-old) on univariable analysis. Overall, older adults were less likely to receive IFX doses ≥10mg/kg q8 weeks (38.4% in older adults vs. 49.7% in younger adults; p< 0.01). On multivariable analysis, age ≥60 years-old (adjOR 1.35, 95%CI 1.20-1.51), IFX dose ≥ 10mg/kg q8 weeks (adjOR 0.53, 95%CI 0.49-0.57) and having ulcerative colitis as compared to Crohn’s disease (adjOR 1.44, 95%CI 1.33-1.57) were independently associated with the development of ATI. Conclusion: Older adults with IBD develop ATI more frequently than younger adults when adjusting for IFX dose and IBD subtype. However, when IFX dose ≥10mg/kg q8 weeks, ATI was significantly less likely to develop among older adults, and occurred in a similar proportion of younger individuals. Further education is needed, highlighting that older adults with IBD are more likely to develop ATI as compared to younger adults, particularly when using lower doses of IFX, and that higher doses may decrease this likelihood.Figure 1.: Percentage of individuals who develop anti-TNF antibodies by age in decades. Table 1. - Multivariable analysis of factors associated with development of Anti-TNF antibodies Odds Ratio [95% CI] Age ≥60 years 1.35 [1.20 – 1.51] Infliximab dose ≥10mg/kg q8 weeks 0.53 [0.49 – 0.57] IBD Subtype Ulcerative Colitis 1.44 [1.33 – 1.57]