ReviewThe AAPS journal2016
Evaluating and Reporting the Immunogenicity Impacts for Biological Products--a Clinical Pharmacology Perspective.
Review in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Animal Pharmacokinetic/Pharmacodynamic Studies (APPS) Reporting Guidelines.European journal of drug metabolism and pharmacokinetics · 2018Guideline
- Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling of Serum M-Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma.Clinical and translational science · 2025Trial
- Antidrug antibodies to adalimumab do not associate with immunologically related adverse events.Frontiers in immunology · 2024Trial
- Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.Blood advances · 2021Trial
- Time-dependent population PK models of single-agent atezolizumab in patients with cancer.Cancer chemotherapy and pharmacology · 2021Trial
- Assessment of the effects of immunogenicity on the pharmacokinetics, efficacy and safety of tildrakizumab.The British journal of dermatology · 2020Trial
- Immune tolerance platforms to mitigate unwanted immune responses.Journal of pharmaceutical sciences · 2026Review
- From anti-drug antibody incidence to clinical relevance: interpreting highly sensitive immunogenicity assays in biosimilars.Bioanalysis · 2026Article
- Advanced assay design for characterizing anti-drug antibody responses in clinical serum samples.Bioanalysis · 2026Review
- First step towards predicting clinical immunogenicity of biologics using in vitro based readouts as animal trial alternatives.Journal of pharmaceutical sciences · 2026Article
- Drawing a line in the sand: impact of analytical choices on anti-drug antibody cut-points and testing outcomes.Bioanalysis · 2026Article
- A modular platform for Sterically Masked Activated Cytokines (SMACks).Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Axatilimab Immunogenicity and Clinical Relevance in Patients with Chronic Graft-Versus-Host Disease.Clinical pharmacology and therapeutics · 2026Article
- Rethinking immunogenicity: an integrated approach reveals the PK/PD impact of pre-existing and drug-sustaining ADA.Bioanalysis · 2026Article
- Artificial lipidation of proteins and peptides: from mechanism to clinical applications.The FEBS journal · 2026Review
- The Need for Clinical Trial Dataset Specifications to Support Clinical Pharmacology Review of Immunogenicity.The AAPS journal · 2026Article
- Retrieval Augmented Generation (RAG) for Natural Language Querying of Immunogenicity Data for Protein Drugs.The AAPS journal · 2026Article
- Optimal transport analysis of high-dimensional flow cytometry data in immuno-oncology.Frontiers in immunology · 2026Article
- Clinical Impacts of Immunogenicity in Approved Antibody Drugs in Japan: A Quantitative Evaluation of Pharmacokinetics, Efficacy, and Safety Outcomes.The AAPS journal · 2025Article
- Assessment of Neutralizing Antibody Activity in Clinical Studies: Use of Surrogate Measurements Instead of Stand-alone Assays.The AAPS journal · 2025Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA's clinical pharmacology review of 121 approved biological products for evaluating and reporting of immunogenicity data. Of the 121 products, 89% (n = 108) reported the incidence of immunogenicity and 49% (n = 59) reported immunogenicity impact on efficacy. However, only 26% (n = 31) reported whether the immunogenicity affected pharmacokinetics. A subset of 16 products reported effects of anti-drug antibodies (ADA) on both systemic clearance and efficacy; 8 of 16 products had increased systemic clearance coinciding with reduced efficacy, and 6 of 16 products had no changes in either clearance or efficacy. Factors contributing to infrequent reporting of the ADA effect on exposure and methods for determining the effect of ADA on exposure are summarized. Measuring ADA and drug concentrations concurrently over time enables the evaluation of ADA impact on pharmacokinetics. Within-subject comparison of concentration data (before vs. after ADA formation) is a useful alternative to between-subject (ADA+ vs. ADA-) comparison when sample size is limited or when the majority of subjects developed ADA. The biological complexity of immune responses presents challenges to quantifying the ADA impact on pharmacokinetics using model-based methods. Our findings support that pharmacokinetic exposure is more sensitive than efficacy endpoints for evaluating ADA effects. A decrease in drug concentration due to formation of ADA during treatment can serve as an early indicator for potential reduced efficacy occurring at a later time.
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What OpenQuestion holds
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.