ArticleAlimentary pharmacology & therapeutics2022
Antibodies-to-infliximab accelerate clearance while dose intensification reverses immunogenicity and recaptures clinical response in paediatric Crohn's disease.
Article in Alimentary pharmacology & therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition position paper on the therapeutic drug monitoring in pediatric inflammatory bowel disease.Journal of pediatric gastroenterology and nutrition · 2025Guideline
- Determination of correlation of clearance with clinical outcomes for inflammatory bowel disease.World journal of gastroenterology · 2026Trial
- Impact of Repeated Antigen Exposure on Humoral Tolerance: Antidrug Antibodies After Single-Dose Versus Multi-dose Adalimumab.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Article
- Is Routine Monitoring of TNF-α Inhibitor Levels and Antibodies in Pediatric IBD Justified in the Era of Personalized Medicine.Journal of clinical medicine · 2026Review
- Genomic Impacts of Biological Exposures.Journal of developmental biology · 2026Review
- Higher Anti-Drug Antibody Levels to Anti-Tumor Necrosis Factor Therapies Are Associated with Treatment Failure in Patients with Inflammatory Bowel Disease.Journal of clinical medicine · 2026Article
- Impact of Proactive Therapeutic Drug Monitoring on Infliximab Maintenance Therapy and Clinical Outcomes in Pediatric Inflammatory Bowel Disease: A Randomized Controlled Trial and Review of Literature.Gastro hep advances · 2026Article
- Switching Between Anti-TNFs and Other Biologic Drugs in Paediatric Inflammatory Bowel Disease: A Narrative Review and Practical Clinical Guide.Journal of inflammation research · 2026Review
- Gradient Boosting Machine-Based Prognostic Model with SurvSHAP Analysis for Predicting Secondary Loss of Response to Infliximab Therapy in Crohn's Disease.Drug design, development and therapy · 2026Article
- Therapeutic Drug Monitoring in Special Circumstances in Inflammatory Bowel Disease.Journal of clinical medicine · 2025Review
- Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease: A Nationwide Survey of Anti-TNF Therapy Practices, Attitudes, and Barriers.Crohn's & colitis 360 · 2025Article
- Integrating early response biomarkers in pharmacokinetic models: A novel method to individualize the initial infliximab dose in patients with Crohn's disease.Clinical and translational science · 2025Article
- Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn's Disease Exhibit Similar Pharmacokinetics.Inflammatory bowel diseases · 2024Article
- From Dose to Exposure: Shifting the Paradigm of Pediatric Clinical Pharmacology Research and Education.Clinical pharmacology and therapeutics · 2024Article
- Infliximab in chronic non-infectious paediatric uveitis refractory to previous biologic therapy.Eye (London, England) · 2024Article
- Biomarkers That Predict Crohn's Disease Outcomes.Journal of the Canadian Association of Gastroenterology · 2024Review
- Precision medicine in inflammatory bowel disease.Precision clinical medicine · 2023Review
- Drug Clearance in Patients with Inflammatory Bowel Disease Treated with Biologics.Journal of clinical medicine · 2023Review
- Precision Dosing of Anti-TNF Therapy in Pediatric Inflammatory Bowel Disease.Current gastroenterology reports · 2023Review
- The Combination of Predictive Factors of Pharmacokinetic Origin Associates with Enhanced Disease Control during Treatment of Pediatric Crohn's Disease with Infliximab.Pharmaceutics · 2023Article
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundAntibodies to infliximab (ATI) are associated with secondary loss of response and increased risk for drug reactions. Limited studies have associated ATI with increased infliximab clearance.
aimsWe assessed the impact of ATI on infliximab clearance and loss of response in an inception paediatric Crohn's disease cohort with 1-year follow-up.
methodsThis multi-centre prospective cohort study collected peak and trough serum infliximab/ATI concentrations from 660 infusions (78 patients) during the first year of therapy. Clinicians were blinded to these research labs. The primary outcome was the difference in infliximab clearance between ATI-positive (ATI) and ATI-negative (no-ATI) patients. Secondary outcomes included pre-treatment predictors of ATI (including HLA-DQA1 genotyping). Clinical remission, loss of response and infliximab clearance were compared between pre-ATI, during ATI and following ATI resolution with MANOVA. Time to ATI was calculated by Cox proportional Hazards model.
resultsATI were detected in 68% (53/78) patients with a median concentration of 76 ng/mL (range 23-1828). Maximum ATI concentration was <200 ng/mL in 73.6% (39/53). Median clearance in ATI patients was higher (with higher clearance if loss of response), compared to no-ATI patients (P < 0.001). Neutrophil CD64 ratio >6 and starting dose <7.5 mg/kg independently predicted ATI in multivariable regression, while HLA-DQA1*05 presence did not. Dose adjustment resolved ATI in 37.5% (12/32) patients with concomitant infliximab concentration and clearance recovery. A maximum ATI level of ≤99 ng/mL predicted ATI resolution (area under the receiver operating curve 0.80 [95% CI 0.64-0.96]).
conclusionsIn this real-world cohort, ATI as low as 23 ng/mL impacted drug clearance. Our data suggest that dose optimisation for low-level ATI can improve infliximab clearance and prevent loss of response.
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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.