{
  "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, UAE"
      ],
      "name": "Shaima Wasim Khan"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, UAE"
      ],
      "name": "Noorah Al Hosani"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, UAE"
      ],
      "name": "Thaer Khaleel Swaid"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, UAE"
      ],
      "name": "Mazin M Edan"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, UAE",
        "Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK",
        "College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, UAE"
      ],
      "name": "Mohammed Nabil Quraishi"
    }
  ],
  "title": "Anti-TNF immunogenicity in a Middle Eastern inflammatory bowel disease cohort: prevalence, predictors and context-specific drug level thresholds",
  "uid": "c0293e35-40ea-5bee-942b-d4a83a9515e8"
}