Trial reportArthritis & rheumatology (Hoboken, N.J.)2021
The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial.
Trial report in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02485769 (A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Sequential Group, Multiple Ascending Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Orally Administered Pf 06650833 In Healthy Subjects), which is not on this map. Cited by 58 papers.
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.
A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Sequential Group, Multiple Ascending Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Orally Administered Pf 06650833 In Healthy Subjects
Who cites it
58 citing papers in PubMed, 89 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of KT-474, a Novel Selective Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degrader, in Healthy Adults.Clinical and translational science · 2025Trial
- The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers.Clinical and translational science · 2024Trial
- IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial.Nature medicine · 2023Trial
- Machine Learning-Driven Drug Repositioning Identifies Putative IRAK4 Inhibitors Through Structure-Based Computational Evaluation.Current issues in molecular biology · 2026Article
- Emerging Therapeutics in Rheumatoid Arthritis.Current rheumatology reports · 2026Review
- Can Phagocytosis, Neutrophil Extracellular Traps, and IFN-α Production in Systemic Lupus Erythematosus Be Simultaneously Modulated? A Pharmacological Perspective.International journal of molecular sciences · 2026Review
- Renal macrophage TLR7 signaling in lupus nephritis: from pathogenic mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control.Nature metabolism · 2025Article
- Inhibition of interleukin-1 receptor-associated kinase (IRAK)-4 provides partial rescue of interleukin-1 beta induced functional and gene expression changes in equine tenocytes.Molecular biology reports · 2025Article
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- IRAK signaling in cancers: mechanisms, targeting, and clinical implications.Expert opinion on investigational drugs · 2025Review
- TLR-induced STK25 activation promotes IRF5-mediated inflammation.Life science alliance · 2025Article
- Dendritic cell heterogeneity and its role in connective tissue diseases.Inflammation and regeneration · 2025Review
- Discovery of novel compound IGYZT01060 for inhibition of IRAK-4 enzyme for the treatment of sepsis.Biotechnology letters · 2025Article
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Review
- Blood-Brain Barrier-Penetrating Nanocarriers Enable Microglial-Specific Drug Delivery in Hypothalamic Neuroinflammation.Advanced healthcare materials · 2025Article
- Review
- Zabedosertib, a novel interleukin-1 receptor-associated kinase-4 inhibitor, shows a favorable pharmacokinetic and safety profile across multiple phase 1 studies.Frontiers in pharmacology · 2025Article
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
27 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo investigate the role of PF-06650833, a highly potent and selective small-molecule inhibitor of interleukin-1-associated kinase 4 (IRAK4), in autoimmune pathophysiology in vitro, in vivo, and in the clinical setting.
methodsRheumatoid arthritis (RA) inflammatory pathophysiology was modeled in vitro through 1) stimulation of primary human macrophages with anti-citrullinated protein antibody immune complexes (ICs), 2) RA fibroblast-like synoviocyte (FLS) cultures stimulated with Toll-like receptor (TLR) ligands, as well as 3) additional human primary cell cocultures exposed to inflammatory stimuli. Systemic lupus erythematosus (SLE) pathophysiology was simulated in human neutrophils, dendritic cells, B cells, and peripheral blood mononuclear cells stimulated with TLR ligands and SLE patient ICs. PF-06650833 was evaluated in vivo in the rat collagen-induced arthritis (CIA) model and the mouse pristane-induced and MRL/lpr models of lupus. Finally, RNA sequencing data generated with whole blood samples from a phase I multiple-ascending-dose clinical trial of PF-06650833 were used to test in vivo human pharmacology.
resultsIn vitro, PF-06650833 inhibited human primary cell inflammatory responses to physiologically relevant stimuli generated with RA and SLE patient plasma. In vivo, PF-06650833 reduced circulating autoantibody levels in the pristane-induced and MRL/lpr murine models of lupus and protected against CIA in rats. In a phase I clinical trial (NCT02485769), PF-06650833 demonstrated in vivo pharmacologic action pertinent to SLE by reducing whole blood interferon gene signature expression in healthy volunteers.
conclusionThese data demonstrate that inhibition of IRAK4 kinase activity can reduce levels of inflammation markers in humans and provide confidence in the rationale for clinical development of IRAK4 inhibitors for rheumatologic indications.
Indexed as
Identifiers
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.