P567 How can we predict the development of antibodies to infliximab in Crohn’s disease?

Abstract

Abstract Background Anti-tumour necrosis factor-α (anti-TNF-α) therapy is an effective treatment for Crohn’s disease (CD). However, treatment failure is common. Our aim was to identify predictors of anti-TNF-α therapy failure. Methods Retrospective single-center study including anti-TNF-α naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate(ESR), c-reactive protein(CRP), faecal calprotectin, infliximab serum concentrations and antibodies to infliximab(ATI). Anti-TNF-α therapy failure was defined as ATI development at 6 or 12 months, absence of clinical response at 6 months, absence of clinical remission or objective response at 12 months. Clinical response was defined as reduction in Harvey-Bradshaw index(HBI) of≥3points comparing with initial value or HBI<5points if initial HBI≥7points and clinical remission as HBI≤4points. Objective response was assessed by endoscopic studies (improvement of mucosal inflammation and absence of deep ulcerations) or imaging (improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement). Results Totally 53 CD patients were included, 49.1%treated with combination of anti-TNF-α and immunomodulatory therapy. Anti-TNF-α therapy failure occurred in 21 patients(39.6%). At 6 months, ATI development occurred in 6 patients(11.3%) and absence of clinical response in 9(17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0%. At 6 months, ATI development was significantly higher in patients with lower infliximab serum concentrations at week 14 (with ATI 5.9±3.2 vs without 14.3±7.7, p<0.001). Additionally, ATI development was significantly higher in patients with a higher initial value of ESR (with ATI median 35 vs without median 13, p=0.045). The infliximab serum concentrations at week 14 (AUC 0.828;p=0.009; sensitivity 0.833, specificity 0.404 for values≤11.6) and the initial value of ESR (AUC 0.754;p=0.045; sensitivity 0.833, specificity 0.468 for values≥15) had very good and good discriminative capacity, respectively, in predicting ATI development. No statistically significant differences were found in initial values of CRP and faecal calprotectin. The other definers of anti-TNF-α therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of biochemical parameters. Conclusion Infliximab serum concentration after induction is the most important factor in ATI development, influencing treatment response, regardless of the combination with immunomodulatory therapy. Higher initial value of ESR can also predict the development of ATI.