RESUMO
BACKGROUND AND AIMS: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. METHODS: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. RESULTS: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. CONCLUSION: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.
RESUMO
BACKGROUND & AIMS: Malnutrition is common in patients eligible for percutaneous endoscopic gastrostomy (PEG). Feeding tube transparietal thickness (TT) may contribute to assess nutritional status. This study aims to: 1) Characterize TT in PEG patients. 2) Determine the association between TT and the currently used tools 3) Define TT best cut-offs to predict undernutrition 4) Assess the correlation between TT and survival. METHODS: Prospective cohort study including patients who underwent PEG. Nutritional assessment was performed using NRS 2002, anthropometry and serum proteins. Anthropometry included body-mass index (BMI), mid upper arm circumference (MUAC), triceps skinfold (TSF) and mid arm muscle circumference (MAMC). TT was measured immediately after PEG and survival was recorded. TT cut-offs were established by comparison with other anthropometric parameters and using the ROC analysis. The correlation between TT and survival was assessed. RESULTS: 227 patients (161 men and 66 women) aged 23-96 years. Most presented head or neck cancer (51.1%). Undernutrition was identified in 57.7% according with BMI. Median TT was 25 mm (IQR = 10). TT was correlated with BMI (R = 0.5), MUAC (R = 0.5), TSF (R = 0.5) and MAMC (R = 0.4) (p < 0.01), respectively, being accurate in predicting undernutrition (AUROC 0.71 ± 0.033, p < 0.01). TT <20 mm showed positive predictive value of 81.6% and specificity of 84.4% to detect undernutrition. TT was correlated with survival (R = 0.1) (p = 0.05). Head or neck cancer patients' survival was significantly lower if TT ≤ 25 mm (p = 0.03). CONCLUSIONS: TT is variable among PEG patients but values below 20-25 mm are suggestive of undernutrition. TT defined in the day of the gastrostomy procedure is the easiest anthropometric parameter that can be obtained from a PEG patient. Due to its higher positive predictive value and correlation with survival, TT should be viewed as an additional anthropometric tool specific for PEG patients, with diagnostic and prognostic value.
