Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of remission and periods of relapse. Patients often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may require hospitalization and even colectomy. Long-term complications of UC include decreased quality of life and productivity and an increased risk of colorectal cancer. Mucosal healing (MH) has gained progressive importance in the management of UC patients. In this article, we review the endoscopic findings that define both mucosal injury and MH, and the strengths and limitations of the scoring systems currently available in clinical practice. The basic mechanisms behind colonic injury and MH are covered, highlighting the pathways through which different drugs exert their effect towards reducing inflammation and promoting epithelial repair. A comprehensive review of the evidence for approved drugs for UC to achieve and maintain MH is provided, including a section on the pharmacokinetics of anti-tumor necrosis factor (TNF)-alpha drugs. Currently approved drugs with proven efficacy in achieving MH in UC include salicylates, corticosteroids (induction only), calcineurin inhibitors (induction only), thiopurines, vedolizumab and anti-TNF alpha drugs (infliximab, adalimumab, and golimumab). MH is of crucial relevance in the outcomes of UC, resulting in lower incidences of clinical relapse, the need for hospitalization and surgery, as well as reduced rates of dysplasia and colorectal cancer. Finally, we present recent evidence towards the need for a more strict definition of complete MH as the preferred endpoint for UC patients, using a combination of both endoscopic and histological findings.info:eu-repo/semantics/publishedVersio

Editorial: variability in adalimumab trough and peak serum concentrations

no abstract availablestatus: publishe

Infliximab Pharmacokinetics are Influenced by Intravenous Immunoglobulin Administration in Patients with Kawasaki Disease.

BackgroundInfliximab, a monoclonal antibody directed against tumor necrosis factor-α, is being evaluated as adjunctive therapy to intravenous immunoglobulin (IVIG) for treatment of young children with acute Kawasaki disease (KD).ObjectiveThe aim of this study was to develop a population pharmacokinetic (PopPK) model for infliximab in children with KD, and to evaluate the impact of covariates on infliximab disposition. Specifically, we wanted to investigate the effect of body weight and IVIG administration on PK parameters.MethodsIn the current PopPK analysis, 70 subjects with a median (interquartile range) age of 2.9 years (1.3-4.4) were included from two randomized controlled trials. Infliximab concentration-time data were best described by a two-compartment model with first-order elimination using non-linear mixed-effects modeling (NONMEM 7.3).ResultsThe clearance, volume of distribution of the central (V1) and peripheral (V2) compartment, and intercompartmental clearance estimates (95% confidence interval) from the PopPK analysis were 0.117 (0.091-0.134) L/day, 0.801 (0.545-0.960) L, 0.962 (0.733-1.759) L, and 0.692 (0.482-1.779) L/day, respectively. Allometric body weight was included on all parameters of the structural model and a covariate analysis revealed that administering infliximab after IVIG, as opposed to before, resulted in a 50% decrease in V2.ConclusionsOur study shows that the timing of infliximab administration relative to IVIG administration affects the disposition of the monoclonal antibody. These results may have important implications for other monoclonal antibodies administered in combination with IVIG for treating inflammatory diseases