Trial reportInternational journal of rheumatic diseases2019
Pharmacodynamic biomarkers and differential effects of TNF- and GM-CSF-targeting biologics in rheumatoid arthritis.
Trial report in International journal of rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3).Annals of the rheumatic diseases · 2023Trial
- Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2).Annals of the rheumatic diseases · 2023Trial
- Pharmacodynamic biomarkers and differential effects of TNF- and GM-CSF-targeting biologics in rheumatoid arthritis.International journal of rheumatic diseases · 2019Trial
- Proteomic and glycosylation biomarkers in rheumatoid arthritis: advancing early diagnosis and precision therapy.Clinical proteomics · 2026Review
- Tofacitinib repairs inflammation and mitochondrial dysregulation in GM-CSF-reprogrammed RA macrophages.Cellular & molecular immunology · 2026Article
- Targeting GM-CSF in Rheumatoid Arthritis: Advances in Cytokine-Directed Immunotherapy and Clinical Implications.Life (Basel, Switzerland) · 2025Review
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- Article
- Crosstalk between CD64EMBO molecular medicine · 2024Article
- Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.Frontiers in immunology · 2024Article
- Epigenetic and transcriptional regulation of CCL17 production by glucocorticoids in arthritis.iScience · 2023Article
- Recent advances in antibody-based immunotherapy strategies for COVID-19.Journal of cellular biochemistry · 2021Review
- Potential clinical biomarkers in rheumatoid arthritis with an omic approach.Auto- immunity highlights · 2021Review
- MicroRNA-23a-5p regulates cell proliferation, migration and inflammation of TNF-α-stimulated human fibroblast-like MH7A synoviocytes by targeting TLR4 in rheumatoid arthritis.Experimental and therapeutic medicine · 2021Article
- Toward Overcoming Treatment Failure in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches.Nature reviews. Immunology · 2020Review
- GM-CSF in inflammation.The Journal of experimental medicine · 2020Review
- Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.Frontiers in immunology · 2020Review
- GM-CSF Primes Proinflammatory Monocyte Responses in Ankylosing Spondylitis.Frontiers in immunology · 2020Article
- Comparative Serum Analyses Identify Cytokines and Hormones Commonly Dysregulated as Well as Implicated in Promoting Osteolysis in MMP-2-Deficient Mice and Children.Frontiers in physiology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe aim of our study was to identify pharmacodynamic biomarkers and assess differential effects of tumor necrosis factor (TNF)- and non-TNF-targeting agents on rheumatoid arthritis (RA) patients with an inadequate response to anti-TNF agents (anti-TNF-IR) in comparison with biologic-naïve patients.
methodsEARTH EXPLORER 2, a phase IIb trial, evaluated golimumab, an anti-TNF antibody, and mavrilimumab, an granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor antibody, in disease-modifying antirheumatic drug (DMARD)-IR and anti-TNF-IR patients. Our current study assessed peripheral protein markers and gene expression levels in association with clinical response post-treatment in two disease strata.
resultsSerum proteomics results indicated the existence of specific pharmacodynamic markers for golimumab and mavrilimumab, regardless of prior anti-TNF treatment. In contrast, both antibodies induced early and sustained suppression of RA disease markers, including interleukin (IL)-6, C-reactive protein, IL2RA, and matrix metalloproteinase 1, in DMARD-IR patients. Golimumab-induced early changes rapidly returned toward baseline concentrations in anti-TNF-IR patients, whereas mavrilimumab-induced changes were maintained through to day 169. RNA sequencing demonstrated gene expression changes at day 169 after administration of mavrilimumab but not golimumab in anti-TNF-IR patients. Additionally, receiver operating characteristic curve and regression analysis showed the association of early IL-6 change and subsequent clinical responses to golimumab in anti-TNF-IR patients.
conclusionOur results revealed golimumab- and mavrilimumab-specific pharmacodynamic biomarkers, and demonstrated differential biomarker-treatment relationships in anti-TNF-IR and DMARD-IR patients, respectively. Early IL-6 change after anti-TNF antibody treatment may be a potential predictive biomarker for selection of different treatment regimens in anti-TNF-IR patients.
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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.