Infliximab and Adalimumab Immunogenicity High in Middle Eastern IBD Cohort; SC Infliximab Shows Lower Rates
Background
Immunogenicity, the development of anti-drug antibodies (ADAs), remains a significant challenge in maintaining treatment efficacy for Inflammatory Bowel Disease (IBD) patients on anti-tumour necrosis factor (anti-TNF) therapies. These biologics, such as infliximab and adalimumab, are cornerstones of IBD management, targeting the pro-inflammatory cytokine TNF-alpha. However, ADAs can lead to reduced drug levels, loss of response, and treatment discontinuation. Data on immunogenicity rates and predictors in Middle Eastern populations are scarce, highlighting a critical gap in understanding context-specific treatment outcomes.
Study Design
This retrospective cohort study analyzed 314 anti-TNF treatment courses (212 infliximab, 102 adalimumab) in 248 IBD patients at a tertiary center in the United Arab Emirates. Immunogenicity was defined by detectable anti-drug antibodies using a drug-tolerant electrochemiluminescent bridging immunoassay with acid dissociation. Researchers tracked patients over a median follow-up of 24.0 months, analyzing drug levels, predictors of immunogenicity, and mechanisms of loss of response. A sensitivity analysis excluded rescued patients, and propensity score matching was used to compare subcutaneous (SC) vs. intravenous (IV) infliximab.
Results
Immunogenicity developed in 28.3% (89/314) of anti-TNF courses over the median 24.0-month follow-up, with a median time to detection of 15.0 months. Infliximab and adalimumab exhibited comparable immunogenicity rates (26.9% vs 31.4%, p=0.425). Immunogenicity-mediated failure was the leading cause of treatment discontinuation, accounting for 48.4% of cases. Pre-event trough levels were significantly lower in immunogenic courses (median 3.0 mcg/mL vs 14.0 mcg/mL; p<0.001). > Exploratory receiver operating characteristic (ROC) analysis identified trough level thresholds of 5.3 mcg/mL for infliximab (AUC 0.880) and 6.4 mcg/mL for adalimumab (AUC 0.861) that predicted immunogenicity with high discrimination. On shared frailty Cox regression, prior surgery emerged as the strongest predictor (HR 1.85, 95% CI 0.94 to 3.64; p=0.074), a signal that strengthened in a sensitivity analysis excluding rescued patients (HR 2.80, 95% CI 1.41 to 5.56; p=0.003). Subcutaneous infliximab showed significantly lower immunogenicity than intravenous infliximab (3.8% vs 18.3%; p=0.013) after propensity score matching, though a new starters-only analysis did not reach statistical significance (p=0.062).
Key Findings
- Immunogenicity developed in 28.3% of anti-TNF courses in Middle Eastern IBD patients.
- Immunogenicity-mediated failure caused 48.4% of treatment discontinuations.
- Immunogenic courses had significantly lower pre-event trough levels (median 3.0 mcg/mL vs 14.0 mcg/mL; p<0.001).
- Trough thresholds of 5.3 mcg/mL (infliximab) and 6.4 mcg/mL (adalimumab) predicted immunogenicity.
- Subcutaneous infliximab showed lower immunogenicity than intravenous infliximab (3.8% vs 18.3%; p=0.013).
Why It Matters
Optimizing anti-TNF therapy in IBD patients, particularly within Middle Eastern populations, necessitates proactive monitoring for immunogenicity. The identified drug level thresholds provide actionable targets for therapeutic drug monitoring (TDM), allowing clinicians to intervene before complete loss of response. The finding that subcutaneous infliximab may have lower immunogenicity than its intravenous counterpart could significantly influence future prescribing practices, potentially improving treatment persistence and patient convenience. This suggests that for certain patients, a shift to SC administration could be a protocol-relevant strategy to mitigate ADA development, though further research is needed to confirm this in larger, prospective cohorts.
inflammatory-bowel-disease
ibd
anti-tnf
immunogenicity
infliximab
adalimumab