P0650Predictors of first Anti-TNF Therapy failure in Inflammatory Bowel Disease: A Single Center Cohort Study

Background Anti-TNF agents have revolutionized the management of immune mediated disorders, including inflammatory bowel disease (IBD). 30% of patients with IBD fail to achieve an initial response (primary loss of response), while up to 50% of initial responders experience secondary loss of response within the first year. These events often necessitate dose escalation or switching to an alternative biologic agent or JAK inhibitors. Methods A single-center retrospective cohort study was conducted at the University Hospital of Ioannina, including patients who received anti-TNF therapy over the past 20 years. The primary objective was to identify predictors of failure of the first anti-TNF agent. Treatment failure was defined as discontinuation due to either primary adverse drug reactions or loss of response (LOR) despite maximal anti-TNF dose escalation (infliximab up to 10 mg/kg every 4 weeks or adalimumab 80 mg weekly). Baseline predictors for LOR were analyzed using Cox regression analysis. Secondary outcomes included the estimation of the percentage of patients who underwent IBD-related surgery as well as the incidence of adverse events resulting in discontinuation and switching of the first anti-TNF agent. Patients with unclassified colitis and patients with LOR and detectable antidrug antibodies were excluded from the study. Results A total of 334 patients who initiated anti-TNF therapy (190 with Crohn’s disease [CD] and 144 with ulcerative colitis [UC]) were included and followed for a median of 10.2 years. LOR after maximal dose escalation occurred in 32% of patients. Adverse drug reactions were observed in 12% of patients, with allergic reactions being the most common. During follow-up, 22.7% of CD patients required surgery for stenotic disease, while 3% of UC patients underwent colectomy due to IBD-related colorectal cancer. In CD, complicated disease phenotype (stricturing or penetrating behavior) was identified as a significant predictor of anti-TNF LOR (p = 0.027) (Table). In UC, female sex emerged as an independent predictor of anti-TNF LOR (p = 0.045) (Table). Conclusion Complicated phenotype in CD and female sex in UC were independent predictors of anti-TNF treatment LOR despite maximal dose escalation. Recognition of such baseline factors may guide more personalized treatment strategies and facilitate earlier therapy optimization or biologic agent switching, ultimately improving long-term outcomes in IBD. Conflict of interest: Dr. Mpakogiannis, Konstantinos: No conflict of interest Chasani, Paraskevi: No conflict of interest Mastorogianni, Ioanna-Nefeli: No conflict of interest Fousekis, Fotios: No conflict of interest Katsanos, Konstantinos: AbbVie, Amgen, Athos, Αenorasis, Biocon, Biogaia, Drugssales Ltd, Epsilon Health, Falk, Faran, Ferring, Genesis, Grifols S.A., Hospital line, Johnson & Johnson, COPER, MSD, Biocon, Pfizer, Potamitis Medicare, Rafarm, Petsiavas, Shire, Takeda, Vianex, Lilly