Trial reportJournal of pharmacokinetics and pharmacodynamics2012
Linking interleukin-6 receptor blockade with tocilizumab and its hematological effects using a modeling approach.
Trial report in Journal of pharmacokinetics and pharmacodynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 47 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of Subcutaneous Sarilumab and Intravenous Tocilizumab Following Single-Dose Administration in Patients With Active Rheumatoid Arthritis on Stable Methotrexate.Journal of clinical pharmacology · 2021Trial
- Population Pharmacokinetic-Pharmacodynamic Relationships of Sarilumab Using Disease Activity Score 28-Joint C-Reactive Protein and Absolute Neutrophil Counts in Patients with Rheumatoid Arthritis.Clinical pharmacokinetics · 2020Trial
- Comparing Model Performance in Characterizing the PK/PD of the Anti-Myostatin Antibody Domagrozumab.Clinical and translational science · 2020Trial
- Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis.Rheumatology (Oxford, England) · 2019Trial
- In vivo affinity and target engagement in skin and blood in a first-time-in-human study of an anti-oncostatin M monoclonal antibody.British journal of clinical pharmacology · 2018Trial
- Population pharmacokinetic and pharmacodynamic analysis of BIIB023, an anti-TNF-like weak inducer of apoptosis (anti-TWEAK) monoclonal antibody.British journal of clinical pharmacology · 2016Trial
- Branched endovascular aneurysm repair complicated by disseminated intravascular coagulation while using tocilizumab.Journal of vascular surgery cases and innovative techniques · 2025Article
- Tocilizumab Dosing for Management of T Cell-Engaging Bispecific Antibody-Related CRS in Patients With R/R B-Cell NHL.Clinical pharmacology and therapeutics · 2025Article
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Increase of Circulating Monocyte-Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage.International journal of molecular sciences · 2022Article
- COVID-19 acute respiratory distress syndrome: A simulation study of the effects of combination therapy with tocilizumab and siltuximab.British journal of clinical pharmacology · 2022Article
- Estimating drug potency in the competitive target mediated drug disposition (TMDD) system when the endogenous ligand is included.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Modeling and simulations of CoViD-19 molecular mechanism induced by cytokines storm during SARS-CoV2 infection.Journal of molecular liquids · 2021Article
- Population Pharmacodynamic Model of Neutrophil Margination and Tolerance to Describe Effect of Sarilumab on Absolute Neutrophil Count in Patients with Rheumatoid Arthritis.CPT: pharmacometrics & systems pharmacology · 2020Article
- Model-free and kinetic modelling approaches for characterising non-equilibrium pharmacological pathway activity: Internalisation of cannabinoid CBBritish journal of pharmacology · 2019Article
- Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans.Clinical pharmacokinetics · 2019Review
- AFIR: A Dimensionless Potency Metric for Characterizing the Activity of Monoclonal Antibodies.CPT: pharmacometrics & systems pharmacology · 2017Article
- Review
- A cell-level model of pharmacodynamics-mediated drug disposition.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- Clinical Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies Approved to Treat Rheumatoid Arthritis.Clinical pharmacokinetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tocilizumab is a recombinant humanized antihuman interleukin-6 receptor monoclonal antibody, which inhibits binding of IL-6 to its soluble (sIL-6R) and membrane-expressed (mIL-6R) receptors. The work investigated whether the observed decline in peripheral neutrophil and platelet counts after tocilizumab administration can be directly explained by tocilizumab IL-6R blockade, thus demonstrating the mechanism of tocilizumab action. Tocilizumab and total sIL-6R concentrations, neutrophil and platelet counts from 4 phase 3 studies in rheumatoid arthritis patients were available. Patients received 4 or 8 mg/kg tocilizumab intravenous infusions every 4 weeks for a total of 6 doses. A population approach was applied to describe the relationship between tocilizumab and sIL-6R concentrations and subsequent changes in neutrophil and platelet counts. Following tocilizumab administration, concentrations of total sIL-6R increased, while neutrophil and platelet counts declined. These changes were transient, with counts returning to their respective baseline levels soon after tocilizumab is eliminated from the body. Tocilizumab concentrations were described by a two compartment model with parallel linear and Michaelis-Menten elimination. The quasi-steady-state target-mediated drug disposition model described tocilizumab relationships to total sIL-6R, which allowed computation of unobserved unbound sIL-6R concentrations. The neutrophil counts were described as a direct function of unbound sIL-6R concentrations. The platelet counts were described by the transit-compartment life-span model with inhibition of production that depended on the unbound sIL-6R concentrations. Thus, the observed changes in sIL-6R, neutrophil, and platelet data are consistent with the tocilizumab mechanism of action and can be fully explained by tocilizumab binding to sIL-6R and mIL-6R.
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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.