Long-term Outcomes of High versus Low Anti-infliximab Antibody Titers in Patients with Crohn's Disease: A Tertiary Referral Center Experience

Introduction: Immune-mediated loss of response to infliximab (IFX) via formation of anti-IFX antibodies (ATI) is a common problem encountered in practice. However, there is a paucity of data regarding long-term implications of low versus high ATI titers on outcomes. In this study, we compare patients with low and high ATI with respect to drug levels, rates of IFX discontinuation, and health care utilization. Methods: This was a retrospective cohort study of CD patients who were exposed to IFX and had IFX trough/antibody levels (TDM) checked between 1/1/2010 and 12/31/2019. Each TDM was classified as either proactive or reactive based on whether it was carried out secondary to loss of response (reactive) or at pre-defined time points to optimize drug levels (proactive). Patients were then dichotomized as “proactive” or “reactive” depending on which TDM method predominated (>50% during study period). ATI and drug levels were selected from the first recorded TDM within the specified time frame. Low and high titer cutoffs were defined by the specified assays (Prometheus, San Diego, CA; Labcorp, Burlington, NC; Esoterix, Austin, TX and ARUP, Salt Lake City, UT). Patients with undetectable ATI were excluded from the study. Patients were compared on objective lab parameters (median albumin, C-reactive protein, fecal calprotectin), overall health care utilization, and endoscopic and histologic outcomes. Results: A total of 66 CD patients (median age at diagnosis 22 years, 58% male) were included in the study, and 37 (56.1%) were found to have high ATI. High ATI were associated with lower median infliximab levels (p = 0.019), increased IFX discontinuation rates (p = 0.026), and higher IBD related health care utilization per year (p= 0.009) (Table 1). The differences in rates of IFX discontinuation were the most prominent within the first 5 years of IFX therapy as shown by the Kaplan- Meier survival curve analysis (Figure 1). When these patients were prospectively followed, those who underwent a predominantly proactive drug monitoring strategy had lower rates of high ATI titer formation (34% vs 59%, p=0.04). Conclusion: In this cohort of CD patients, high ATI titers showed higher rates of IFX discontinuation and health care utilization, as well as lower IFX drug levels, when compared to patients who had low ATI titers. This study further emphasizes the need for proactive optimization of IFX while treating patients with CD, in order to achieve better results, especially during the first few years of therapy.Figure 1.: Kaplan-Meier survival curve comparing Infliximab discontinuation rates when comparing high versus low antibody titers.Table 1.: Univariable analysis of factors/co-variates associated with high versus low antibody titers (significant values bolded and italicized); n: population, %: percentage, IFX: infliximab, IBD: inflammatory bowel disease, BMI: body mass index, IQR: inter quartile range.