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Showing 41 results for “Preclinical”.

November 2023

Bimekizumab Treatment in Patients With Active Axial Spondyloarthritis: 52-week Efficacy and Safety from the Randomised Parallel Phase 3 BE MOBILE 1 and BE MOBILE 2 Studies

Ann Rheum Dis. 2023;83(2):199–213 doi 10.1136/ard-2023-224803

Baraliakos, et al. present data from two Phase 3 studies, BE MOBILE 1 and BE MOBILE 2, that investigated the clinical efficacy and safety of bimekizumab in axSpA patients. They found that bimekizumab had sustained and consistent efficacy in patients with nr-axSpA and r-axSpA.

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February 2021

Baricitinib Inhibits Structural Joint Damage Progression in Patients with Rheumatoid Arthritis – A Comprehensive Review

Arthritis Res Ther 2021;23(1):3.

MRI studies have shown that BARI reduces joint inflammation and damage in patients with moderate-to-severe active RA. This review summarises the effects of BARI on structural joint damage progression and the mechanisms underlying these effects, using MRI data from across the clinical trial program. Early preclinical animal models showed a significant reduction in joint inflammation, ankle width, and bone resorption. Efficacy and safety of BARI have been confirmed in an extensive programme, inclu...

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October 2020

Preclinical characterisation of itacitinib, a Novel Selective Inhibitor of JAK1, for the Treatment of Inflammatory Diseases

European Journal of Pharmacology. 2020 Oct 15;885:173505. doi: 10.1016/j.ejphar.2020.173505

Itacitinib is an orally active JAK inhibitor and effectively delayed disease onset, reduced symptom severity, and accelerated recovery of inflammatory diseases in mouse models. Covington M et al demonstrated itacitinib’s high selectivity for JAK 1, its inhibition on IL-2 induced T cell proliferation and JAK/STAT signalling, its ability to also inhibit of the JAK/STAT pathway in response to IL-6 stimulation, and its effect on rat adjuvant induced arthritis model. The study used recombinant enzym...

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February 2020

Osteoimmunology In Rheumatoid and Psoriatic Arthritis: Potential Effects of Tofacitinib on Bone Involvement

Clin Rheumatol. 2020

Data showing that TOF can inhibit unbalanced osteoclastogenesis in RA suggests that targeting the JAK-STAT pathway can halt bone erosion, as TOF has been shown to reduce articular bone erosion in RA and PsA.The authors in this review summarise current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signalling in bone homeostasis while discussing the evidence on the benefit of TOF on prevention of bone involvement in RA and PsA...

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June 2019

Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models

J Immunol 2019;202:2888–2906. DOI: 10.4049/jimmunol.1800583

BTK is involved in both adaptive and innate immune responses and mediates signalling of several immune receptors of relevance to RA and SLE pathogenesis. Targeting BTK is a promising approach therefore for autoimmune disorders with aberrant B cell responses. Evobrutinib is a novel, highly specific, and irreversible BTK inhibitor. In vivo and animal models showed that evobrutinib modulated B cell and innate immune cell activation, was efficacious, and prevented joint damage. The potency of evobru...

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The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis

Arthritis Res Ther. 2015 May 20;17(1):135. [Epub ahead of print]

Over the last decade, there has been a shift in treatment outcomes for RA; moving from symptom control to achieving remission. The TNF inhibitors have revolutionised treatment in this way, yet there is still a proportion of patients who fail to improve or reach remission. As such, new molecules for the treatment of RA are needed to be developed.This study investigates the in vitro and in vivo properties of ALX-0061, a bispecific Nanobody with a high affinity and potency for IL-6R.Positive pharma...

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April 2015

Super-enhancers delineate disease-associated regulatory nodes in T cells

Nature. 2015 Feb 16. doi: 10.1038/nature14154. [Epub ahead of print]

Transcription machinery (proteins responsible for activating or ‘switching off’ genes) is not distributed in the genome in a symmetrical (or even) manner. Some parts of the genome, so called super-enhancers (SEs), accumulate an exceptionally high level of proteins relevant to the regulation of transcription (i.e. the machinery is concentrated in particular parts of the genome). In this paper, the investigators asked about the locale of these regions in the genome of T cells. Then they addressed...

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January 2015

IL-6 stimulates intestinal epithelial proliferation and repair after injury

PLoS One. 2014 Dec 5;9(12):e114195. doi: 10.1371/journal.pone.0114195. eCollection 2014.

IL-6 is an inflammatory cytokine known to contribute to a number of autoimmune diseases such as RA. Therapies targeting the soluble IL-6 receptor have now become effective treatments for RA. However, one unforeseen, yet rare, potential complication of anti-IL-6 therapy is bowel perforation. Yet within the intestine, IL-6 protects intestinal epithelial cells from apoptosis during prolonged inflammation.

The authors hypothesized that IL-6 may have beneficial properties in wound response/rep...

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December 2014

Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate

Ann Rheum Dis. 2015;74(2):333–340

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies.

This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...

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The activity of JAK-STAT pathways in rheumatoid arthritis: constitutive activation of STAT3 correlates with interleukin 6 levels

Rheumatology (Oxford). 2014 Nov 17. pii: keu430. [Epub ahead of print]

Non-response, parenteral administration and cost to produce are all aspects associated with the currently available anti-cytokine agents for RA. These related factors mean that alternative drugs are now being developed. Recent developments in therapeutic drugs to treat RA have focused on Janus kinases (JAKs) and signal transducer and activator of transcription (STATs) transcription pathways. Several cytokines that regulate immune responses in RA, such as IFN-g, IL-6 and IL-10, activate JAK-STAT ...

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