To characterize immunogenicity rates, predictors, and loss of response mechanisms in a real-world cohort of patients with inflammatory bowel disease receiving anti-TNF therapies, addressing the lack of data from Middle Eastern populations.
Approach:
Study Design: Retrospective cohort study including 314 anti-TNF treatment courses in 248 patients at a tertiary center in the UAE.
Immunogenicity Definition: Defined by detectable anti-drug antibodies using a drug-tolerant electrochemiluminescent bridging immunoassay.
Data Analysis: Analyzed drug levels, predictors, and loss of response mechanisms.
Key Findings:
Immunogenicity developed in 28.3% of treatment courses over a median follow-up of 24 months.
Infliximab and adalimumab had comparable immunogenicity rates (26.9% vs 31.4%; p=0.425).
Immunogenicity-mediated failure was the leading cause of treatment 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 thresholds for predicting immunogenicity were identified: 5.3 mcg/mL for infliximab and 6.4 mcg/mL for adalimumab.
Interpretation:
Immunogenicity patterns in this Middle Eastern cohort are consistent with Western data, suggesting pharmacokinetic rather than population-specific determinants.
Limitations:
The study is retrospective and may be subject to biases inherent in such designs.
The cohort was limited to a single tertiary center in the UAE, which may affect generalizability.
Conclusion:
The findings suggest a potential benefit of proactive therapeutic drug monitoring and indicate that subcutaneous infliximab may offer an immunogenic advantage warranting further validation.
