ArticleFrontiers in immunology2022
Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons.Seminars in immunopathology · 2026Review
- Benefit and risk associated with interleukin-6 receptor inhibitor administration during severe COVID-19: a retrospective multicentric study.Scientific reports · 2026Observational
- Advances in understanding the tumor microenvironment of neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Case Report: Targeted interleukin-6 blockade by siltuximab for cytokine release syndrome control and infection limitation in thirteen patients treated with bi-specific T-cell engagers.Frontiers in immunology · 2026Article
- Longitudinal Comparison of Calprotectin and C-Reactive Protein in Rheumatoid Arthritis: Real-World Evidence Across Three Targeted Therapies.Diagnostics (Basel, Switzerland) · 2025Article
- C-reactive protein modulates lipid mediators in a pro-inflammatory direction.Journal of inflammation (London, England) · 2025Article
- Real-world data of siltuximab for Chinese patients with iMCD: combination with BCD regimen as a potential approach for severe cases.Annals of hematology · 2025Article
- Decoding Health: Exploring Essential Biomarkers Linked to Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes Mellitus.Biomedicines · 2025Review
- Efficacy and safety of anti-interleukin-6 treatment in familial Mediterranean fever: a systematic literature review.Reumatologia · 2025Review
- Toxicities Associated with Systemic Administration of Interleukin-6 in Wistar Albino Rats.Journal of experimental pharmacology · 2025Article
- Exploring the therapeutic potential of interleukin-6 receptor blockade in autoimmune diseases using drug target mendelian randomization.Immunogenetics · 2024Article
- New perspectives in cancer immunotherapy: targeting IL-6 cytokine family.Journal for immunotherapy of cancer · 2023Review
Corrections and comments
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Authors and funding
8 authors at 7 institutions in 3 countries.
Funding
Abstract
Background: Dysregulated interleukin (IL)-6 production can be characterised by the levels present, the kinetics of its rise and its inappropriate location. Rapid, excessive IL-6 production can exacerbate tissue damage in vital organs. In this situation, therapy with an anti-IL-6 or anti-IL-6 receptor (IL-6R) monoclonal antibody, if inappropriately dosed, may be insufficient to fully block IL-6 signalling and normalise the immune response. Methods: We analysed inhibition of C-reactive protein (CRP) - a biomarker for IL-6 activity - in patients with COVID-19 or idiopathic multicentric Castleman disease (iMCD) treated with tocilizumab (anti-IL-6R) or siltuximab (anti-IL-6), respectively. We used mathematical modelling to analyse how to optimise anti-IL-6 or anti-IL-6R blockade for the high levels of IL-6 observed in these diseases. Results: IL-6 signalling was insufficiently inhibited in patients with COVID-19 or iMCD treated with standard doses of anti-IL-6 therapy. Patients whose disease worsened throughout therapy had only partial inhibition of CRP production. Our model demonstrated that, in a scenario representative of iMCD with persistent high IL-6 production not controlled by a single dose of anti-IL-6 therapy, repeated administration more effectively inhibited IL-6 activity. In a situation with rapid, high, dysregulated IL-6 production, such as severe COVID-19 or a cytokine storm, repeated daily administration of an anti-IL-6/anti-IL-6R agent, or alternating daily doses of anti-IL-6 and anti-IL-6R therapies, could neutralise IL-6 activity. Conclusion: In clinical practice, IL-6 inhibition should be individualised based on pathophysiology to achieve full blockade of CRP production. Funding: EUSA Pharma funded medical writing assistance and provided access to the phase II clinical data of siltuximab for analysis.
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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.