Publications

View and download slide summaries of the latest original articles focusing on therapies in immune-mediated inflammatory diseases including rheumatology, dermatology, and gastroenterology. All materials produced by the team are subsequently reviewed and approved by individual Steering Committee members.

May 2023

Evaluation of BMS-986142, a Reversible Bruton’s Tyrosine Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis: A Phase 2, Randomised, Double-blind, Dose-ranging, Placebo-controlled, Adaptive Design Study

Lancet Rheumatol 2023;5:e263–73 doi 10.1016/S2665-9913(23)00089-9

Conaghan PG,

Nowak M,

Du S,

Luo Y,

Fura A,

Investigators from a phase 2 study concluded that further investigation with BMS-986142 (a novel BTK) in people with RA is not necessary.

Keywords:

BTK,
Phase 2

January 2020

Safety, Tolerability, Pharmacokinetics, Target Occupancy, and QT Analysis of the Novel BTK Inhibitor Evobrutinib in Healthy Volunteers

Clin Transl Sci . 2020 Mar;13(2):325-336. doi: 10.1111/cts.12713. Epub 2019 Nov 29.

Mackenzie H and Johne A

In this first in-human phase I, double-blind, placebo-controlled trial, the Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib was well-tolerated, showed linear and time-independent PK, induced long-lasting BTK inhibition, and was not associated with prolongation of QT/QTc interval in healthy subjects. Evobrutinib is an oral BTK inhibitor that has demonstrated efficacy in pre-clinical and autoimmune disease models. BTK is a key regulator of B cell receptor and Fc receptor signalling, and a rat...

Keywords:

May 2014

Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants

Ann Rheum Dis Published Online First 24 April 2014 doi:10.1136/annrheumdis-2013-204143

Hartkamp LM,

Fine JS,

van Es IE et al

Bruton’s tyrosine kinase, a downstream target of PI3K signalling, has been shown to be crucial in the B lymphocyte and myeloid cell contribution to murine models of arthritis. Synovial tissue samples were taken from biologically naïve RA (n=16) and PsA (n=12) patients in order to assess the expression of BTK. Separate RA synovial explants (n=8) were used to assess the effects of the specific BTK inhibitor RN486. BTK was expressed at equivalent levels in both RA and PsA synovial tissue, however e...

Keywords:

January 2014

The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss

Bone 2014;60:8-15

Shinohara M,

Chang BY,

Buggy JJ et al

Ibrutinib is a first-in-class, orally available Btk (Bruton’s tyrosine kinase) inhibitor which has been shown to be effective in the treatment against certain types of leukemia and autoimmune disorders. Btk regulates the expression of genes involved in the differentiation and function of osteoclasts, and therefore inhibiting Btk suppresses osteoclastic bone resorption. Results from in vitro testing showed the suppressive effects on osteoclasts and murine models of RA showed ibrutinib treatment p...

Keywords:

October 2013

Ibrutinib and novel BTK inhibitors in clinical development

Journal of Hematology & Oncology 2013;6:59

Akinleye A,

Chan Y,

Mukhi N et al.

Bruton’s tyrosine kinase (BTK) is a part of the cytokine signalling pathways involved in malignancies and autoimmune disorders.. Akinleye et al. provide a review of all the current BTK inhibitors in preclinical and clinical trials for B-cell malignancies and autoimmune disorders, including rheumatoid arthritis. Particular focus is placed on ibrutinib, a novel human BTK-inhibitor, currently in phase III clinical trials. The authors also discuss four new compounds with potential indications in rh...

Keywords:

August 2013

Targeting the SYK-BTK axis for the treatment of immunological and hematological disorders: recent progress and therapeutic perspectives

Pharmacol Ther. 2013 May; 138(2):294–309

Tan SL,

Liao C,

Lucas MC,

et al

This review focuses on targeting spleen tyrosine kinase (SYK) and Bruton’s tyrosine kinase (BTK) inhibitors as potential immunomodulatory agents for the treatment of autoimmune and inflammatory disorders with SYK inhibition showing encouraging efficacy in patients with RA. The paper describes the role of SYK and BTK in several therapy areas including autoimmune diseases, allergic inflammatory disorders and haematological cancers as well as their role in innate immunity and regulators of adaptive...