Aberrant Mucin Expression Profiles Associate With Pediatric Inflammatory Bowel Disease Presentation and Activity.

Background: Intestinal mucosal healing is nowadays preferred as the therapeutic endpoint in inflammatory bowel disease (IBD), but objective measurements at the molecular level are lacking. Because dysregulated mucin expression is suggested to be involved in mucosal barrier dysfunction in IBD, we investigated mucin expression in association with barrier mediators and clinical characteristics in colonic tissue of a pediatric IBD population.

Methods: In this cross-sectional monocentric study, we quantified messenger RNA (mRNA) expression of mucins, intercellular junctions, and cell polarity complexes in inflamed and noninflamed colonic biopsies from pediatric IBD (n = 29) and non-IBD (n = 15) patients.

A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab.

Background: Combining vedolizumab with a rapid-onset drug such as cyclosporine is a novel combination treatment for severe steroid-resistant ulcerative colitis (UC). This prospective study describes the efficacy and safety of cyclosporine in conjunction with vedolizumab in patients with severe, steroid-resistant UC with 1 year of follow-up.

Methods: Seventeen steroid-resistant UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks.

Infliximab Concentrations during Induction Are Predictive for Endoscopic Remission in Pediatric Patients with Inflammatory Bowel Disease under Combination Therapy.

Objectives: To study infliximab (IFX) pharmacokinetics in children with inflammatory bowel disease (IBD) during induction therapy to predict outcome and explore if other covariates influenced outcome.

Study Design: All children with IBD starting IFX therapy (5 mg/kg at weeks 0, 2, 6, and 12) for active luminal disease from May 2017 to May 2019 were included and followed prospectively. Patients were sampled at multiple timepoints during induction (trough concentrations and peak concentration at weeks 0, 2, 6, and 12, and intermediate concentration at weeks 1-4).

The effect of aging on infliximab exposure and response in patients with inflammatory bowel diseases.

Aims: Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab exposure, efficacy and safety.

Methods: Retrospective case-control data of patients receiving infliximab induction treatment were analysed.

Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab Concentrations.

Background And Aims: Some patients with ulcerative colitis [UC] do not respond to vedolizumab treatment despite adequate drug exposure in serum. This study aimed to investigate vedolizumab in tissue and questioned whether insufficient tissue exposure could explain non-response in UC patients with adequate serum vedolizumab concentrations.

Methods: A paired serum sample and colonic mucosal biopsy was collected from 40 UC patients [20 endoscopic responders, 20 non-responders] at week 14 of vedolizumab treatment.

Endoscopic remission can be predicted by golimumab concentrations in patients with ulcerative colitis treated with the changed label.

Background: In 2018, the European Medicines Agency (EMA) replaced a fixed 50 mg every 4-week maintenance regimen of golimumab for ulcerative colitis (UC) patients weighing <80 kg with new, flexible dosing that allows reactive dose optimization to 100 mg if clinically needed. We analyzed the endoscopic remission rates and pharmacokinetics of this new dosing regimen in real-life settings.

Methods: We prospectively recruited 30 consecutive (17 with body weight <80 kg) patients with UC who received golimumab with the new EMA label.

Modelling of the relationship between infliximab exposure, faecal calprotectin and endoscopic remission in patients with Crohn's disease.

Aims: Evidence for the benefits of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring of infliximab in patients with Crohn's disease (CD) remains scarce. We aimed to develop a population (pop)PK/PD model to characterise the infliximab dose-exposure-biomarker-response (faecal calprotectin [fCal] and endoscopic remission [ER]) relationship.

Methods: Data were obtained from 116 patients with CD in a phase 4 dose-escalation study.

Evaluating an easy sampling method using dried blood spots to determine vedolizumab concentrations.

An association between vedolizumab (VDZ) trough concentrations and therapeutic outcome has been observed in patients with inflammatory bowel diseases. VDZ samples are typically collected via venous sampling for therapeutic drug monitoring (TDM), but can alternatively be collected via dried blood spot (DBS) samples, which can be used for intensive sampling to investigate pharmacokinetic profiles. Therefore, we have developed a DBS method for determining VDZ concentrations and validated this method by comparing VDZ measurements in paired DBS and venous patient samples.

Successful Infliximab Treatment is Associated With Reversal of Clotting Abnormalities in Inflammatory Bowel Disease Patients.

Background And Goals: Active inflammatory bowel diseases (IBD) represent an independent risk factor for venous thromboembolism. The authors investigated the hemostatic profile of IBD patients before and after induction treatment with infliximab, vedolizumab, and methylprednisolone.

Study: This prospective study included 62 patients with active IBD starting infliximab, vedolizumab, and/or methylprednisolone, and 22 healthy controls (HC).

Anti-infliximab antibodies: How to compare old and new data?

Background: Anti-drug-antibodies (ADA) against infliximab are frequently measured in patients receiving infliximab treatment with loss of response and undetectable infliximab concentrations. Different ADA bridging assays (1st generation, 2nd generation and ready-to-use kit) have been developed successively and were applied over the last 10 years, making comparison between ADA concentrations very challenging. A cutoff of 8 μg/ml was established to discriminate low from high ADA concentrations using the 1st generation ADA bridging assay.

Influence of Drug Exposure on Vedolizumab-Induced Endoscopic Remission in Anti-Tumour Necrosis Factor [TNF] Naïve and Anti-TNF Exposed IBD Patients.

Background And Objectives: Vedolizumab has demonstrated efficacy and safety in patients with Crohn's disease [CD] and ulcerative colitis [UC]. Endoscopic outcome data are limited, especially in anti-tumour necrosis factor [TNF] naïve patients. The present study compared endoscopic outcome in anti-TNF naïve and exposed patients, and explored if this was affected by drug exposure.

Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?

Biologicals introduced a major shift in the treatment of patients suffering from inflammatory bowel diseases. Despite providing a tight disease control for many patients, a considerable proportion of patients will fail to respond favorably to treatment or will lose response over time. Therapeutic drug monitoring emerged as a valuable tool to guide clinical decision making as serum drug concentrations have been linked to outcomes.

Evaluating Efficacy, Safety, and Pharmacokinetics After Switching From Infliximab Originator to Biosimilar CT-P13: Experience From a Large Tertiary Referral Center.

Background: The use of infliximab biosimilar CT-P13 has increased in patients with inflammatory bowel disease. Nevertheless, doubts about switching from infliximab originator to biosimilar still exist among patients and health care professionals.

Methods: Our tertiary referral center underwent a mandatory switch from infliximab originator to CT-P13 in 2017.

A Population Pharmacokinetic and Exposure-Response Model of Golimumab for Targeting Endoscopic Remission in Patients With Ulcerative Colitis.

Background: Unlike other anti-tumor necrosis factor alpha antibodies, golimumab does not deliver on its promise of effectiveness for treating patients with ulcerative colitis. We investigated the value of therapeutic drug monitoring for optimizing golimumab therapy.

Methods: We analyzed the golimumab pharmacokinetics data of 56 patients with moderate to severe ulcerative colitis.

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

Background: Very little is known about the impact of the wash-out period on the pharmacokinetics of a second-line biologic.

Objective: The objective of this article is to explore the impact of two different wash-out periods on the pharmacokinetics of vedolizumab and infliximab.

Methods: Patients switching from infliximab to vedolizumab were retrospectively identified.

Early vedolizumab trough levels predict combined endoscopic and clinical remission in inflammatory bowel disease.

Background: The relationship between vedolizumab trough levels and combined endoscopic and clinical remission is unknown.

Objective: To compare vedolizumab trough levels in patients with and without combined remission within the first year of treatment.

Methods: We prospectively collected vedolizumab trough levels in 51 consecutive patients (28 Crohn's disease (CD) and 23 ulcerative colitis (UC)) before all infusions up to week 22, and at weeks 38 and 54, with concentrations measured after study completion.

Monitoring a Combination of Calprotectin and Infliximab Identifies Patients With Mucosal Healing of Crohn's Disease.

Background & Aims: In the TAILORIX trial, no benefit could be shown by infliximab dose escalation based on pharmacokinetic (infliximab serum concentrations) and pharmacodynamic (biomarkers and symptoms) monitoring compared with dose escalation based on symptoms alone in patients with Crohn's disease (CD). We investigated whether integration of pharmacokinetic and pharmacodynamic monitoring can be used to evaluate responses to infliximab induction and maintenance therapy, based on findings from endoscopy.

Methods: We performed a post hoc analysis of patients with CD included in a trial to test the effects of infliximab dose escalation, based on biomarkers and serum concentrations of infliximab, on symptoms (the Study Investigating Tailored Treatment With Infliximab for Active Crohn's Disease trial; n = 122).

Long-term Clinical Effectiveness of Ustekinumab in Patients with Crohn's Disease Who Failed Biologic Therapies: A National Cohort Study.

Background: Ustekinumab [UST] was recently approved in Europe for the treatment of moderate to severe Crohn's disease [CD]. Long-term real-world data are currently scarce for CD patients previously exposed to several biologics.

Methods: This is an observational, national, retrospective multicentre study.

Pharmacodynamic Monitoring of Biological Therapies in Chronic Inflammatory Diseases.

Background: Psoriasis, psoriatic arthritis, spondyloarthritis, rheumatoid arthritis, ulcerative colitis, and Crohn disease share similar underlying pathophysiological processes, providing the opportunity to treat the patients using similar biological therapies. Failure of biological treatments due to underexposure can be managed by therapeutic drug monitoring. Adjusting the treatment based on pharmacokinetic monitoring can be further improved by taking pharmacodynamic parameters such as clinical and molecular markers into account.