INFLIXIMAB AND ADALIMUMAB SERUM TROUGH CONCENTRATIONS THRESHOLD ASSOCIATED WITH DEEP REMISSION IN INFLAMMATORY BOWEL DISEASE.

Objective: Deep remission (DR) defined by clinical-biomarker remission and mucosal healing (MH) has emerged as a new therapeutic target in inflammatory bowel disease (IBD). The aim of this study was to define an optimal cut-off concentration for IFX and ADA during maintenance therapy associated with DR. The secondary objective, was to evaluate the influence of variables on anti-TNF concentrations and DR.

Methods: Retrospective study including 120 and 122 patients IBD diagnosed who received maintenance therapy with IFX and ADA. Biomarker remission was considered by C-reactive protein (CRP)<5 mg/L and fecal calprotectin (CF)<100 mcg/g. Crohn's disease (CD) clinical remission was defined by a Harvey Bradshaw score<5 and MH by a simple endoscopic score for CD (SES-CD)<3.  In ulcerative colitis (UC), it was defined as a Mayo total score<3 and Mayo endoscopic subscore<2. Receiver operating characteristic (ROC) test was performed to determine drug concentration thresholds associated with DR. Anti-TNF concentrations were classified into quartiles. X2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics and serological factors associated with DR.

Results: Anti-TNF concentrations were higher in patients with DR, in IFX (4.4, IQR: 3.3-6.5 vs 2.3, IQR: 1.1-4.2 μg/mL, P<0.005) and ADA (6.3, IQR: 4.2-8.2 vs 3.9, IQR: 2.4-5.5 μg/mL, P<0.005). A ROC identified a concentration threshold of 3.1 μg/mL in IFX (area under the ROC curve [AUROC], 0.72) and 6.3 μg/mL in ADA (AUROC, 0.75) associated with DR. Factors associated with the highest quartiles of serum IFX concentration were: elevated body mass index (BMI), absence of previous IBD-surgery, CRP<5 mg/L, and FC<100 μg/g. In ADA, higher quartiles were related to concomitant immunosuppressants, low BMI, absence of previous IBD-surgery, and CRP<5 mg/L and FC<100 μg/g. Multivariate regression identified FC<100 μg/g, CRP<5mg/L, IFX ≥3.1μg/mL and ADA concentrations ≥6.3μg/mL as factors significantly associated with DR.  CONCLUSIONS: Trough IFX and ADA concentrations, CRP<5mg/L and FC<100 μg/g are associated with DR during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for IFX and ADA respectively, were identified as DR predictors.