The serological support for early diagnosis and differential diagnosis of inflammatory bowel diseases (IBDs) is actually very limited. In this study, we evaluated the performance of a promising multiparametric method including either well-established and newly developed biomarkers. We conducted a multicenter cross-sectional study at the Gastroenterology Units of Udine (Italy), Rijeka (Croatia) and Belgrade (Serbia). Sera was collected from IBD patients, and autoantibody profiles were determined using a mosaic cell and tissue-based indirect immunofluorescence (IIF) method simultaneously investigating anti-saccharomyces cerevisiae antibodies (ASCAs), anti-atypical perinuclear neutrophilic antibodies (P-ANCAs), anti-pancreatic antigens antibodies (PABs) and anti-goblet cells antibodies (GAB). The study finally enrolled 156 patients with IBD: 100 affected by Crohn’s disease (CD) and 56 by ulcerative colitis (UC). Twenty age-sex matched blood donors (BDs) were included as controls. PAB (anti-CUZD1 and/or anti-GP2 antibodies) were present in 24 CD patients versus none of the UC patients or BDs (24% sensitivity, 100% specificity). As regards CD patients, combined positivity of PAB and ASCA (sensitivity 84%, specificity 71.4%) performed better than ASCA alone. Colon involvement (87.5% vs. 60.5%; p = 0.014), deep mucosal lesions (58.3% vs. 25.0%; p = 0.002) and need for biologic therapies (79.2% vs. 46.1%; p = 0.005) were significantly more prevalent in PAB-positive than in PAB-negative CD patients. Multivariate analysis identified PAB positivity (OR = 3.67; 95%CI = 1.29–10.46) and anti-CUZD1 in particular (OR = 3.54; 95%CI = 1.08–11.63) as significant risk factors for deep mucosal lesion development in CD. A multiparametric diagnostic approach appears very useful to better characterize IBD patients. PABs, whether isolated or combined with other autoantibodies, may support differential diagnosis but above all facilitate the selection of CD patients at risk for more severe disease.

Introduction: The serological support to early diagnosis and differential diagnosis of inflammatory bowel diseases (IBD) is actually very limited. In this study we evaluated the performance of a promising multiparametric method including either well established and newly developed biomarkers. Methods: This multicenter retrospective observational study finally enrolled 156 patients with IBD, 100 affected by Crohn’s disease (CD) and 56 by ulcerative colitis (UC) recruited at the Gastroenterology Units of Udine (Italy), Rijeka (Croatia) and Belgrade (Serbia). Twently age-sex matched blood donors (BD) were included as controls. Autoantibody profiles were determined using a mosaic cell and tissue-based indirect immunofluorescence (IIF) method simultaneously investigating: anti-saccharomyces cerevisiae antibodies (ASCA), anti-atypical perinuclear neutrophilic antibodies (P-ANCA), anti-pancreatic antigens antibodies (PAB) and anti-goblet cells antibodies (GAB). Results: PAB (anti-CUZD1 and/or anti-GP2 antibodies) were present in 24 CD patients versus none of UC patients or BD (24% sensitivity, 100% specificity). As regards CD patients, combined positivity of PAB and ASCA (sensitivity 84%, specificity 71.4%) performed better than ASCA alone. Colon involvement (87.5% vs. 60.5%; p=0.014), deep mucosal lesions (58.3% vs. 25.0%; p=0.002) and need for biologic therapies (79.2% vs. 46.1%; p=0.005) were significantly more prevalent in PAB-positive than in PAB-negative CD patients. Multivariate analysis identified PAB positivity (OR=3.67; 95%CI=1.29-10.46) and anti-CUZD1 in particular (OR=3.54; 95%CI=1.08-11.63) as significant risk factors for deep mucosal lesions development in CD. Conclusion: A multiparametric diagnostic approach appears very useful to better characterize IBD patients. PAB, isolated or combined with other autoantibodies, may support both differential diagnosis and selection of CD patients at risk for more severe disease.

Background/Objectives: Adalimumab (ADM) is a recombinant, fully human monoclonal antibody that exhibits pronounced inter- and intra-individual pharmacokinetic variability attributed to several factors. This study aims to externally evaluate the published ADM population pharmacokinetic models and their potential use in clinical practice, as well as to develop novel population pharmacokinetic model. Methods: Literature search was conducted using PubMed to identify ADM population pharmacokinetic models. Data from 195 patients with Crohn’s disease treated at the University Medical Center “Zvezdara”, Serbia, were used for the external evaluation of previously published models. In addition, the development of the new population pharmacokinetic model incorporated informative priors derived from the best-performing published model. Nonlinear mixed-effects modeling was performed in NONMEM^® (versions 7.6) for both prediction- and simulation-based diagnostics of existing models, as well as for the development of a new model. Results: Eight published pharmacokinetic models of ADM were included in the external evaluation. Although none of the models satisfied both population-level and normalized prediction distribution error (NPDE) diagnostic criteria, individual-level performance was acceptable: median prediction errors (MDPEs) were within ±20% across all studies, and median absolute prediction errors (MDAPEs) were below 30% in most cases (7 of 8 studies). The best-performing model was identified and implemented as a priori information in subsequent model development. A one-compartment model using with first-order absorption and elimination best described the data. The apparent clearance (CL/F) was estimated at 0.334 L/day, while informative priors were used for V/F and the effect of anti-drug antibodies (ADAs) on CL/F. Covariate analysis on CL/F identified C-reactive protein (CRP) and dosing regimen as statistically significant predictors (p < 0.01). Conclusions: The previous pharmacokinetic models of ADM exhibited suboptimal performance in population-level metrics and simulation-based diagnostics, while individual-level metrics showed substantial improvement. The newly developed model of ADM highlights associations among immunogenicity, drug pharmacokinetics, and inflammatory burden.