infliximab pharmacokinetics

OBJECTIVES: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-TNF treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients. METHODS: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF...

Here, we describe a 7-year-old girl who was diagnosed with an early-onset Crohn's disease in the setting of COVID-19 illness. Her disease process responded poorly to standard infliximab dosing, necessitating repeat hospitalizations and red blood cell transfusions. Remission was subsequently induced using a personalized infliximab pharmacokinetic profile based on therapeutic drug monitoring. While the initial data does not support a link, several case reports suggest an association between COVID-19 illness and de-novo development of IBD, especially in young female patients...

BACKGROUND AND OBJECTIVE: Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy. METHODS: A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available...

BACKGROUND: Patients with Crohn's disease (CD) who lose response to biologics experience reduced quality of life (QoL) and costly hospitalizations. Precision-guided dosing (PGD) provides a comprehensive pharmacokinetic (PK) profile that allows for biologic dosing to be personalized. We analyzed the cost-effectiveness of infliximab (IFX) PGD relative to two other dose intensification strategies (DIS). METHODS: We developed a hybrid (Markov and decision tree) model of patients with CD who had a clinical response to IFX induction...

INTRODUCTION: The only biologic therapy currently approved to treat moderate to severe Crohn's disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically important to develop novel strategies that maximise treatment effectiveness in this population. There is growing evidence that rates of sustained corticosteroid-free clinical remission, endoscopic healing and drug durability considerably improve when patients receive early anti-TNF dose optimisations guided by reactive or proactive therapeutic drug monitoring and pharmacodynamic monitoring...

BACKGROUND: Therapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing. OBJECTIVE: The aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance...

BACKGROUND AND OBJECTIVE: Efficacy of infliximab in children with inflammatory bowel disease can be enhanced when serum concentrations are measured and further dosing is adjusted to achieve and maintain a target concentration. Use of a population pharmacokinetic model may help to predict an individual's infliximab dose requirement. The aim of this study was to evaluate the predictive performance of available infliximab population pharmacokinetic models in an independent cohort of Dutch children with inflammatory bowel disease...

INTRODUCTION: We evaluated baseline Clearance of anti-tumor necrosis factors and human leukocyte antigen variant (HLA DQA1*05) in combination as poor prognostic factors (PPF) of pharmacokinetic (PK) origin impacting immune response (formation of antidrug antibodies) and disease control of inflammatory bowel disease (IBD) patients treated with infliximab or adalimumab. METHODS: Baseline Clearance was estimated in IBD patients before starting treatment using weight and serum albumin concentrations...

BACKGROUND: Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies. METHODS: Patients with Crohn's disease or ulcerative colitis received CT‑P13 IV loading doses (5 mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CT‑P13 IV (5 mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group')...

Psoriasis pathogenesis involves TNF-α, IL-23 and IL17, against which biologics have been highly effective. Among the five TNF-α inhibitors available for psoriasis, namely infliximab, adalimumab, etanercept, golimumab and certolizumab pegol (CZP), CZP has a unique mechanism of action due to its structure. As CZP lacks the Fc region, it does not cross the placenta and can be safely used in pregnant women. Its PEGylated nature allows for longer distribution time in tissues, potentially leading to a longer-lasting effect compared with other TNF-α inhibitors...

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...

INTRODUCTION: The biosimilar CT-P13, the first and only subcutaneous (SC) infliximab formulation, is recommended for patients with psoriatic arthritis (PsA) and can be administered as a maintenance treatment, to be started 4 weeks after the induction treatment with 2 intravenous (IV) infliximab infusions. OBJECTIVE: To evaluate treatment with SC infliximab without prior IV infusion induction to meet patient needs. MATERIALS AND METHODS: After approval by the ethics review board and based on the schedule approved for rheumatoid arthritis, SC induction was performed with infliximab CT-P13 120 mg weekly for 4 weeks, followed by an injection of 120 mg every 2 weeks...

BACKGROUND: The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD). METHODS: This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort)...

Multisystem Inflammatory Syndrome in children (MIS-C) is a rare and novel pediatric complication linked to COVID-19 exposure, which was first identified in April 2020. A small n, Sequential, Multiple Assignment, Randomized Trial (snSMART) was applied to the Multisystem Inflammatory Syndrome Therapies in Children Comparative Effectiveness Study (MISTIC) to efficiently evaluate multiple competing treatments. In the MISTIC snSMART study, participants are randomized to one of three interventions (steroids, infliximab or anakinra), and potentially re-randomized to the remaining two treatments depending on their response to the first randomized treatment...

Aggregation has been widely described as a factor contributing to therapeutic antibody immunogenicity. Although production of high-affinity anti-drug antibodies depends on the activation of CD4 T lymphocytes, little is known about the T-cell response induced by antibody aggregates, especially for aggregates produced in mild conditions resulting from minor handling errors of vials. Large insoluble infliximab (IFX) aggregates produced in severe elevated temperature stress conditions have been previously shown to induce human monocyte-derived dendritic cell (moDC) maturation...

BACKGROUND: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. AIMS: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. METHODS: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics...

Precision-dosing models forecast infliximab doses to achieve targeted trough concentrations in patients with inflammatory bowel disease (IBD). These models have shown to reduce non-response and improve patient outcomes. We compared infliximab doses determined by iDOSE® precision-dosing with standard dosing, and the associated drug costs, in patients with IBD. In this retrospective study, IBD patients treated with infliximab every eight weeks at 5 mg/kg were included. An infliximab dose was named dose X if three previous infliximab doses, laboratory values including trough infliximab concentrations and the patient's weight were recorded...

BACKGROUND: The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly investigated. The aim of this study was to investigate factors predicting IFX-BioS trough levels (TLs). RESEARCH DESIGN AND METHODS: IBD children with an indication to start IFX-BioS were included in this prospective observational study (January 2021-June 2022). TLs were measured at the 4th and 6th infusions and correlated with several covariates...

OBJECTIVE: Immunogenicity against anti-TNF antibodies usually leads to loss of response. We aimed to evaluate the efficacy of clinical strategies to improve clinical remission and pharmacokinetics upon detection of anti-drug antibodies (ADA). METHODS: Inflammatory bowel disease (IBD) patients with ADA against infliximab or adalimumab were identified through a single centre database search covering 2004-2022. Criteria for successful intervention upon ADA detection (baseline) were clinical remission after 1 year without further change in strategy...

Physiologically based pharmacokinetic (PBPK) models can be used to leverage physiological and in vitro data to predict monoclonal antibody (mAb) concentrations in serum and tissues. However, it is currently not known how consistent predictions of mAb disposition are across PBPK modelling platforms. In this work PBPK simulations of IgG, adalimumab and infliximab were compared between three platforms (Simcyp, PK-Sim, and GastroPlus). Accuracy of predicted serum and tissue concentrations was assessed using observed data collected from the literature...