ArticleThe AAPS journal2017
Magnitude of Increased Infliximab Clearance Imposed by Anti-infliximab Antibodies in Crohn's Disease Is Determined by Their Concentration.
Article in The AAPS journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Multi-model averaging improves the performance of model-guided infliximab dosing in patients with inflammatory bowel diseases.CPT: pharmacometrics & systems pharmacology · 2022Trial
- Impact of Antibodies Against Polyethylene Glycol on the Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukaemia: A Population Pharmacokinetic Approach.European journal of drug metabolism and pharmacokinetics · 2022Trial
- Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.Drugs in R&D · 2017Trial
- Population Pharmacokinetics Analysis of Infliximab in up to 10-Year-Old Patients with Paediatric Inflammatory Bowel Disease: Label-Recommended Dose Fails to Achieve Therapeutic Target Concentration.Clinical pharmacokinetics · 2026Article
- Article
- Mechanism-Based Modeling Approaches to Quantify the Effect of Immunogenicity on the Pharmacokinetics of Therapeutic Proteins in Drug Development.CPT: pharmacometrics & systems pharmacology · 2025Review
- Factors associated with anti-drug antibody production in ankylosing spondylitis patients treated with the infliximab biosimilar CT-P13.Journal of rheumatic diseases · 2025Article
- Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics.Journal of clinical medicine · 2023Review
- Population Pharmacokinetic Model of Adalimumab Based on Prior Information Using Real World Data.Biomedicines · 2023Article
- Ulcerative Colitis and Acute Severe Ulcerative Colitis Patients Are Overlooked in Infliximab Population Pharmacokinetic Models: Results from a Comprehensive Review.Pharmaceutics · 2022Review
- Infliximab Treatment Does Not Lead to Full TNF-α Inhibition: A Target-Mediated Drug Disposition Model.Clinical pharmacokinetics · 2022Article
- External Model Performance Evaluation of Twelve Infliximab Population Pharmacokinetic Models in Patients with Inflammatory Bowel Disease.Pharmaceutics · 2021Article
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- Favorable Outcomes and Anti-TNF Durability After Addition of an Immunomodulator for Anti-Drug Antibodies in Pediatric IBD Patients.Inflammatory bowel diseases · 2021Article
- Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Importance of Feedback and Feedforward Loops to Adaptive Immune Response Modeling.CPT: pharmacometrics & systems pharmacology · 2018Review
- Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic Proteins.Journal of pharmaceutical sciences · 2018Review
- Anti-drug Antibodies Against a Novel Humanized Anti-CD20 Antibody Impair Its Therapeutic Effect on Primary Biliary Cholangitis in Human CD20- and FcγR-Expressing Mice.Frontiers in immunology · 2018Article
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibodies (Abs) against infliximab (IFX) increase IFX clearance and can result in treatment failure and acute hypersensitivity reactions. However, interpretation of their clinical value is complicated by individual differences in Ab responses and methods used for quantification. The increase in IFX clearance imposed by anti-IFX Abs has generally been evaluated using a binary classification, i.e., positive or negative. This analysis aimed to investigate if anti-IFX Ab concentrations provide a more adequate prediction of alterations in clearance. Data originated from a clinical trial on Crohn's disease patients with IFX treatment failure. The trial was not originally designed for pharmacokinetic analysis. Therefore, published pharmacokinetic models were utilized as priors to enable covariate investigation. The impact of anti-IFX Abs on clearance was assessed using different mathematical relationships and exploiting information from two different quantification assays, measuring semi-quantitative "total" or "unbound neutralizing" concentrations of anti-IFX Ab, respectively. Inclusion of anti-IFX Ab status/concentration improved the model's performance for all investigated relationships. The anti-IFX Ab concentrations were superior to the binary classifications, indicating that the magnitude of increase in IFX clearance imposed by anti-IFX Abs closely relates to their concentration. Furthermore, total anti-IFX Ab concentrations appeared superior to the unbound neutralizing fraction in identifying high clearance individuals. Simulations showed that even at low concentrations, anti-IFX Abs lead to sub-therapeutic IFX concentrations, supporting a need of treatment interventions in all anti-IFX Ab positive patients. The developed model can serve as a basis for further investigations to refine treatment recommendations for patients with anti-IFX Abs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.