Anti-TNF immunogenicity in a Middle Eastern inflammatory bowel disease cohort: prevalence, predictors and context-specific drug level thresholds.

Abstract

Objective: Anti-tumour necrosis factor (anti-TNF) immunogenicity remains a major barrier to treatment persistence in inflammatory bowel disease, yet data from Middle Eastern populations are lacking. We characterised immunogenicity rates, predictors and loss of response mechanisms in a real-world cohort.

Methods: This retrospective cohort study included 314 anti-TNF treatment courses (212 infliximab, 102 adalimumab) in 248 patients at a tertiary centre in the United Arab Emirates. Immunogenicity was defined by detectable anti-drug antibodies on a drug-tolerant electrochemiluminescent bridging immunoassay with acid dissociation. Drug levels, predictors and loss of response mechanisms were analysed.

Results: Immunogenicity developed in 28.3% (89/314) of courses over median follow-up of 24.0 months (median time to detection 15.0 months, IQR 8.0-36.0). Infliximab and adalimumab had comparable rates (26.9% vs 31.4%; p=0.425). Immunogenicity-mediated failure was the leading cause of discontinuation (48.4%). Pre-event trough levels were significantly lower in immunogenic courses (median 3.0 vs 14.0 mcg/mL; p<0.001). Exploratory receiver operating characteristic thresholds of 5.3 mcg/mL for infliximab (area under the curve (AUC) 0.880) and 6.4 mcg/mL for adalimumab (AUC 0.861) predicted immunogenicity with high discrimination. On shared frailty Cox regression, prior surgery was the strongest predictor (HR 1.85, 95% CI 0.94 to 3.64; p=0.074). A sensitivity analysis excluding rescued patients strengthened the surgery signal (HR 2.80, 95% CI 1.41 to 5.56; p=0.003). Subcutaneous infliximab showed lower immunogenicity than intravenous infliximab (new starters 1/25 (4.0%), switchers 1/33 (3.0%) vs IV 57/212 (26.9%)); after propensity score matching on five covariates, the difference remained significant (3.8% vs 18.3%; p=0.013), though a new starters-only analysis did not reach significance (p=0.062).

Conclusion: Immunogenicity patterns in this Middle Eastern cohort are consistent with Western data, supporting pharmacokinetic rather than population-specific determinants. These findings suggest a potential benefit of proactive therapeutic drug monitoring and that subcutaneous infliximab may offer an immunogenic advantage warranting prospective validation.