Infliximab in young paediatric IBD patients: it is all about the dosing.
Ontology highlight
ABSTRACT:
SUBMITTER: Jongsma MME
PROVIDER: S-EPMC7666662 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Infliximab in young paediatric IBD patients: it is all about the dosing.
Jongsma Maria M E MME Winter Dwight A DA Huynh Hien Q HQ Norsa Lorenzo L Hussey Seamus S Kolho Kaija-Leena KL Bronsky Jiri J Assa Amit A Cohen Shlomi S Lev-Tzion Raffi R Van Biervliet Stephanie S Rizopoulos Dimitris D de Meij Tim G J TGJ Shouval Dror S DS Wine Eytan E Wolters Victorien M VM Martinez-Vinson Christine C de Ridder Lissy L
European journal of pediatrics 20200819 12
Infliximab (IFX) is administered intravenously using weight-based dosing (5 mg/kg) in inflammatory bowel disease (IBD) patients. Our hypothesis is that especially young children need a more intensive treatment regimen than the current weight-based dose administration. We aimed to assess IFX pharmacokinetics (PK), based on existing therapeutic drug monitoring (TDM) data in IBD patients < 10 years. TDM data were collected retrospectively in 14 centres. Children treated with IFX were included if IF ...[more]
Similar Datasets
Project description:Efficacy of infliximab in treatment on inflammatory bowel disease and factors affecting the therapeutic
| PRJEB22028 | ENA
Project description:Colonic mucosal microbiota and association of bacterial taxa with the expression of host antimicrobial peptides in pediatric ulcerative colitis
| PRJEB38527 | ENA
Project description:Microbiome of Paediatric IBD Patients
| PRJEB45397 | ENA
Project description:AimsThe therapeutic failure of infliximab therapy in patients with ulcerative colitis remains a challenge even 2 decades after its approval. Therapeutic drug monitoring (TDM) has shown value during maintenance therapy, but induction therapy has still not been explored. Patients may be primary nonresponders or underexposed with the standard dosing regimen. We aimed to: (i) develop a population pharmacokinetic-pharmacodynamic model; (ii) identify the best exposure metric that predicts mucosal healing; and (iii) build an exposure-response (ER) model to demonstrate model-based dose finding during induction therapy with infliximab.MethodsData were retrospectively collected from a clinical database. A total of 583 samples, from 204 patients, was used to develop a population pharmacokinetic model to generate exposure metrics for subsequent ER modelling. A subset of 159 patients was used to develop a logistic regression ER model, describing the relationship between infliximab exposure and ordered transitions between Mayo endoscopic subscore (MES) 3, 2 and ≤1 (baseline to post-induction).ResultsA 1-compartment population pharmacokinetic model with interindividual and interoccasion variability was found to fit the data best. Covariates influencing exposure were C-reactive protein, albumin, baseline MES, fat-free mass, concomitant corticosteroid use and pancolitis. The cumulative area under the infliximab concentration-time curve until endoscopy (CAUCendoscopy ) was found to be the best exposure metric for predicting mucosal healing (baseline MES >1 and post-induction MES ≤1). The model predicted that 70% of patients will attain mucosal healing with infliximab administered at days 0, 14 and 42 and a target CAUCendoscopy of 3752 mg/L*day at day 84.ConclusionsTDM-based dose individualisation targeting CAUCendoscopy has the potential to improve the effectiveness of infliximab during induction therapy.
| S-EPMC6422726 | biostudies-literature
Project description:Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). This has important implications for patient management and development of novel biologic therapies. The objective of this study was to perform a systematic review and meta-analysis of studies that reported clinical outcomes and IFX levels according to patients' ATI status.MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for eligible studies. Quality assessment was undertaken using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Raw data from studies meeting inclusion criteria was pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias.Thirteen studies met the inclusion criteria, and reported results in 1,378 patients with IBD. All included studies had a high risk of bias in at least one quality domain. The pooled risk ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs was 3.2 (95% confidence interval (CI): 2.0-4.9, P<0.0001), when compared with patients without ATIs. This effect estimate was predominantly based on data from patients (N=494) with Crohn's disease (RR: 3.2, 95% CI: 1.9-5.5, P<0.0001). Data only from patients with ulcerative colitis (n=86) exhibited a non-significant RR of loss of response of 2.2 (95% CI: 0.5-9.0, P=0.3) in those with ATIs. Heterogeneity existed between studies, in both methods of ATI detection, and clinical outcomes reported. Three studies (n=243) reported trough serum IFX levels according to ATI status; the standardized mean difference in trough serum IFX levels between groups was -0.8 (95% CI -1.2, -0.4, P<0.0001). A funnel plot suggested the presence of publication bias.The presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Published studies on this topic lack uniform reporting of outcomes. High risk of bias was present in all the included studies.
| S-EPMC3561464 | biostudies-literature
Project description:Infliximab was the first monoclonal antibody used in the treatment of inflammatory bowel disease (IBD). Over several years, this antitumour necrosis factor (TNF) treatment proved its efficacy in both induction and maintenance therapy. In many cases this biological treatment stopped the progression of the disease, probably also decreasing morbidity and hospitalization rates, and improving patients' comfort. When the patent on infliximab started to expire, the first biosimilar of a monoclonal antibody was introduced onto the pharmacological market. Biosimilar infliximab was studied in rheumatology and proved a high similarity to the reference drug. Based on extrapolation, biosimilars were approved to treat adult and paediatric IBD patients. Biosimilar infliximab, mainly because of its lower cost, has started to be in common use in Europe. The first studies have shown a similar efficacy and safety profile in comparison with reference drug. Biosimilar infliximab is raising hopes for improving the availability of this effective treatment.
| S-EPMC4984328 | biostudies-literature
Project description:Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.
| S-EPMC9966915 | biostudies-literature
Project description:Antioxidants are privileged candidates for the development of adjuvants able to improve the efficiency of pharmacological therapies, particularly for chronic inflammatory syndromes. During the last 20 years, anti-TNFα (tumor necrosis factor alpha) monoclonal antibodies infusion has been the biological therapy most frequently administered but there is still large space for improvement in disease remission rates and maintenance. In this context, nutritional bioactive compounds contained in dietary patterns or included as supplements, may act as adjuvants for the induction and maintenance of IBD (inflammatory bowel diseases) remission. To verify this possibility, a single-center preliminary study (SI-CURA, Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA) was designed and carried out to evaluate whether a daily administration of purple corn supplement could improve the response to Infliximab (IFX) infusion of IBD patients with both Crohn's disease (CD) and ulcerative colitis (UC). A cohort of 47 patients was enrolled in the study. Biological samples were collected before the first and the third IFX infusion. All patients received nutritional guidelines, 27 of them received commercial red fruit tea with low anthocyanins content, while 20 received a purple corn supplement with a high anthocyanin content. Results show that the administration of an antioxidant-enriched purple corn supplement could improve IFX-mediated disease remission in terms of circulating inflammatory markers. Comparison between CD and UC patients revealed that, at this anthocyanin dosage, the purple corn extract administration improved the IFX response in CD but not in UC patients. Our results may pave the way for a new metacentric study of CD patients, recruiting a wider cohort and followed-up over a longer observational time.
| S-EPMC8773281 | biostudies-literature
Project description:Infliximab is commonly used in inflammatory bowel disease (IBD), however, differences in clinical response among patients are common. Several studies have considered the possibility that these differences are caused by genetic variability even if no unique marker has been yet identified in pediatric patients. We evaluated the impact of two candidate single-nucleotide polymorphisms (SNPs) rs396991 in FCGR3A and rs1800629 in TNFα genes on infliximab response in an Italian cohort of 76 pediatric patients with IBD. Results showed that patients with the variant FCGR3A allele had a reduced clinical response at the end of induction (p value = 0.004), at 22 weeks (p value = 0.001), and at 52 weeks of treatment (p value = 0.01). A significant association between the FCGR3A variant and median infliximab levels measured during maintenance therapy was also observed: patients with wild type genotype had higher infliximab levels compared to patient with variant allele. Furthermore, patients with the variant allele had a higher probability to produce antidrug antibodies (ADAs). No association was found among the TNFα SNP, clinical response, and infliximab levels. This study addressed for the first time in pediatric patients with IBD, the association of FCGR3A SNP, infliximab response, and ADA production.
| S-EPMC8604212 | biostudies-literature
Project description:Infliximab, a monoclonal antibody tumor necrosis factor-alpha inhibitor, is an effective therapy that is indicated for the treatment of patients with Crohn's disease. Although dose escalation from 5 mg/kg to 10 mg/kg is allowed according to the prescribing label of infliximab, conflicting results exist regarding the rate at which this escalation may occur, which may affect payers and providers.The goal of this exploratory study was to characterize and quantify the rate of infliximab dose escalation in a sample of patients with Crohn's disease.Administrative claims data from patients with Crohn's disease in a large mid-Atlantic managed care organization were collected and used to target and recruit providers into a chart review study of infliximab dosing. Data from the charts of 161 patients with Crohn's disease who were receiving infliximab between 2006 and 2010 were extracted. Patients were grouped into an infliximab dose-escalation group or a dose-stable group based on these data. The evidence of any infliximab dose ?7.5 mg/kg or evidence of a mean maintenance interval of 42 days or less resulted in the placement of a patient in the dose-escalation group, with the balance of patients comprising the stable-dose group.A total of 925 infliximab infusions were captured from 161 patients. Of the 161 patients identified, 110 had at least 4 infusions, and 4 had missing data; therefore, only 106 (66%) patients were qualified for the final infliximab dosing analysis. A total of 18 (17%) of these patients had evidence of infliximab dose escalation (dose-escalation group), and the remaining 88 (83%) patients had a consistent 5-mg/kg dose and schedule (stable-dose group). Of the 18 patients in the dose-escalation group, 9 (50%) had a decrease in maintenance interval, whereas 12 (66.7%) patients had an increase in their dosage. A total of 3 (16.7%) patients had both an increase in dose and a reduction in maintenance interval.Infliximab has been shown to be a cost-effective treatment for patients with Crohn's disease. The rate of infliximab dose escalation in this study was within the lower range of published estimates for this medication. Studies using larger sample sizes are needed to validate the findings of the current study. In addition, studies that are focused on quantifying and describing the nature of infliximab dose escalation may be useful in the development of successful patient-treatment matching algorithms.
| S-EPMC4049116 | biostudies-other