ArticleArthritis research & therapy2011
The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells.
Article in Arthritis research & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
120 citing papers in PubMed, 230 citations in OpenAlex.
- A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Dose and Multiple-Rising-Dose Study of the BTK Inhibitor TAK-020 in Healthy Subjects.Clinical and translational science · 2021Trial
- A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers.British journal of clinical pharmacology · 2017Trial
- Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants.European journal of clinical pharmacology · 2017Trial
- Trial
- Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes.Blood · 2013Trial
- Trial
- Review
- Targeting Bruton's Tyrosine Kinase (BTK) in Autoimmunity: Achievements, Opportunities and Challenges.Drug design, development and therapy · 2026Review
- The Bruton tyrosine kinase inhibitor acalabrutinib aborts ongoing acute food-induced anaphylactic reactions in humanized mice.The Journal of allergy and clinical immunology · 2025Article
- Current and future landscape of Bruton tyrosine kinase inhibitors in allergy.The Journal of allergy and clinical immunology · 2025Review
- Dissecting the Ability of Siglecs To Antagonize Fcγ Receptors.ACS central science · 2024Article
- Bruton's tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder.Journal of neuroinflammation · 2023Article
- Bruton's tyrosine kinase inhibition reduces disease severity in a model of secondary progressive autoimmune demyelination.Acta neuropathologica communications · 2023Article
- New small molecules in dermatology: for the autoimmunity, inflammation and beyond.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Article
- Pyrazole-containing pharmaceuticals: target, pharmacological activity, and their SAR studies.RSC medicinal chemistry · 2022Review
- Bruton's Tyrosine Kinase Inhibitors: The Next Frontier of B-Cell-Targeted Therapies for Cancer, Autoimmune Disorders, and Multiple Sclerosis.Journal of clinical medicine · 2022Review
- Review
- Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect.Experimental hematology & oncology · 2022Review
- Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions.Allergy · 2022Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
introductionThe aim was to determine the effect of the Bruton tyrosine kinase (Btk)-selective inhibitor PCI-32765, currently in Phase I/II studies in lymphoma trials, in arthritis and immune-complex (IC) based animal models and describe the underlying cellular mechanisms.
methodsPCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis (CIA), collagen antibody-induced arthritis (CAIA), reversed passive anaphylactic reaction (RPA), and passive cutaneous anaphylaxis (PCA). Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis, and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells, cytokine and chemokine production in monocytes/macrophages, degranulation of mast cells and its subsequent cytokine/chemokine production.
resultsPCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED(50) of 2.6 mg/kg/day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models, infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly, the bone and cartilage integrity of the joints were preserved. PCI-32765 reduced inflammation in the Arthus and PCA assays. In vitro, PCI-32765 inhibited BCR-activated primary B cell proliferation (IC(50) = 8 nM). Following FcγR stimulation, PCI-32765 inhibited TNFα, IL-1β and IL-6 production in primary monocytes (IC(50) = 2.6, 0.5, 3.9 nM, respectively). Following FcεRI stimulation of cultured human mast cells, PCI-32765 inhibited release of histamine, PGD(2), TNF-α, IL-8 and MCP-1.
conclusionsPCI-32765 is efficacious in CIA, and in IC models that do not depend upon autoantibody production from B cells. Thus PCI-32765 targets not only B lymphocytes but also monocytes, macrophages and mast cells, which are important Btk-expressing effector cells in arthritis.
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.