Novel Therapeutic Targets in Axial Spondyloarthritis

Worth, Claudia; Bowness, Paul; Al-Mossawi, Hussein

doi:10.1007/s40674-018-0095-1

Cited by 8 publications

(5 citation statements)

References 65 publications

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“…The pan-JAK inhibitor tofacitinib and the JAK1 inhibitors filgotinib and upadacitinib have all reported promising phase 2 results in AS [ 42–44 ], with phase 3 results awaited. A number of other novel therapeutic options are in various stages of development for axSpA, including anti-cytokine agents targeting other components of the IL-17 superfamily and different pathways, and small molecule agents targeting transcription factors, intracellular signalling and epigenetic modification [ 45 ].…”

Section: Biologic Dmards In Axspamentioning

confidence: 99%

Treatment strategies in axial spondyloarthritis: what, when and how?

Fragoulis

Siebert

2020

Rheumatology

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There have been major advances in the management of axial spondyloarthritis (axSpA) with the introduction of effective biologic agents targeting TNF and IL-17A. Clinicians now have more choice but, despite treatment recommendations, are still faced with significant uncertainty when deciding on the optimal treatment strategy for an individual patient in clinical practice. Management of axSpA typically requires both non-pharmacological and pharmacological interventions. NSAIDs remain the first line drug therapies for axSpA with proven efficacy for symptomatic management but uncertainty remains regarding their optimal long-term use relating to radiographic progression and safety in axSpA. To-date there are no head-to-head trials of biologics in axSpA. Clinicians need to consider other factors, including extra-articular manifestations, comorbidities, safety and radiographic progression when deciding on which biologic to recommend for an individual patient. This article will explore the evidence relating to these factors and highlight areas of unmet need.

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Section: Biologic Dmards In Axspamentioning

confidence: 99%

Treatment strategies in axial spondyloarthritis: what, when and how?

Fragoulis

Siebert

2020

Rheumatology

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“…Moreover, GM-CSF may also promote the release of proinflammatory chemokines such as CCL17 in an IRF4-dependent pathway. Of note, GM-CSF also seems to contribute to joint pain by enhancing the response of sensory nerve fibres to mechanical stimuli [ 233 ]. On this basis, GM-CSF inhibitors may represent a new therapeutic target for managing patients with axial-SpA.…”

Section: Therapeutic Targets In Axial-spamentioning

confidence: 99%

Uncovering the Underworld of Axial Spondyloarthritis

Vescovo

Venerito

Iannone

et al. 2023

IJMS

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Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

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“…GM-CSF is a pro-inflammatory cytokine that has a pleiotropic effect on myeloid cells including monocytes, macrophages, and dendritic cells and mediates their differentiation into a more inflammatory phenotype. 49 In health GM-CSF plays an important role in injury or infection by mediating the interface between innate and adaptive immunity. GM-CSF is induced by other cytokines including IL-1β, IL-6 and TNFα, which are produced by a variety of cells.…”

Section: Granulocyte-macrophage Colony-stimulating Factor (Gm-csf)mentioning

confidence: 99%

Promising Treatment Options for Axial Spondyloarthritis: An Overview of Experimental Pharmacological Agents

Tahir¹,

Byravan²,

Fardanesh³

et al. 2021

JEP

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Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that predominantly affects the axial skeleton. All patients receive conservative management measures which include physiotherapy, patient education and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Those with significant active disease will require escalation of their treatment with the use of biologics. Currently, there are five approved TNF inhibitors and two approved IL-17 inhibitors for use in axSpA. However, despite this up to 40% of patients do not respond or are intolerant to current available treatment. This leaves a significant number of patients with uncontrolled disease and unmet need for additional therapies. Though many drug classes have been trialed for axSpA they show poor efficacy; however, over the last few years there are three which demonstrate much greater promise as novel therapies for axSpA, these include dual neutralization of IL-17A and IL-17F, Janus kinase (JAK) inhibitors, and granulocytemacrophage colony-stimulating factor (GM-CSF) inhibitors. This article reviews the evidence for these novel emerging therapeutic options for axSpA.

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Novel Therapeutic Targets in Axial Spondyloarthritis

Cited by 8 publications

References 65 publications

Treatment strategies in axial spondyloarthritis: what, when and how?

Treatment strategies in axial spondyloarthritis: what, when and how?

Uncovering the Underworld of Axial Spondyloarthritis

Promising Treatment Options for Axial Spondyloarthritis: An Overview of Experimental Pharmacological Agents

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