Publications

Guselkumab provides sustained domain-specific and comprehensive efficacy using composite indices in patients with active psoriatic arthritis

Rheumatology (Oxford) 2022 doi: 10.1093/rheumatology/keac375

Coates LC,

Ritchlin CT,

Gossec L,

Helliwell PS,

Rahman P,

Kollmeier AP,

Xu XL,

Shawi M,

Karyekar CS,

Contré C,

Noël W,

Sheng S,

Wang Y,

Xu S,

Mease PJ

This analysis found that patients with active PsA who receive treatment with guselkumab can achieve robust and sustained low disease activity or remission. In reaching this conclusion investigators sought to evaluate the efficacy of guselkumab for the treatment of active PsA through the use of composite indices.

Keywords:

• IL-23,
• Guselkumab,
• Efficacy

A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition

Rheumatology (Oxford). 2021. Epub ahead of print. doi: 10.1093/rheumatology/keab740.

McInnes IB,

Szekanecz Z,

McGonagle D,

Maksymowych WP,

Pfeil A,

Lippe R,

Song IH,

Lertratanakul A,

Sornasse T,

Biljan A,

Deodhar A

JAK inhibitors are likely to become an important part of the overall treatment paradigm for spondyloarthritis (SpA).Although not fully understood, the pathogenesis of SpA is complex and thought to involve both environmental and genetic factors that together elicit a chronic inflammatory response involving the innate and adaptive immune systems. Several different cytokines, TNF, IL-17A, IL-12/23 and IL-23, which are directly/indirectly affected by JAK molecules, are involved in the pathogenesis o...

Keywords:

• JAK,
• Basic Science,
• Review

Pathogenetic Insights from the Treatment of Rheumatoid Arthritis

Lancet 2017;389:2328–37 DOI 10.1016/S0140-6736(17)31472-1

McInnes I,

Schett G

This review paper examines the understanding gained from looking at the effects of specific immune interventions in the treatment of RA.The introduction of novel IL-6 agents has provided the ideal opportunity to explore the distinct effect of cytokine inhibition, as opposed to receptor inhibition, at the molecular level. Mechanistic insights into TNF could also be obtained in the future with advanced molecular and informatics approaches, and future biopsy studies will be important to explore the...

Keywords:

• Basic Science,
• Review

Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation

Nature. 2014;510(7503):157–161.

Riol-Blanco L,

Ordovas-Montanes J,

Perro M,

et al.

The abnormal activation of skin immune cells, such as dermal dendritic cells (DDCs) and interleukin (IL)-17-producing γδ T (γδT17) cells, by IL-23 is known to provoke psoriasis-type inflammation. What is less well known is how peripheral nerves regulate cutaneous immune responses. In this study, IL-23-dependent psoriasis-like inflammation was induced in mice to help determine the precise molecular mechanism of neuroimmune communication in the skin. Findings indicate nocic...

Keywords:

• Preclinical,
• MOA

Cytokine networks—towards new therapies for rheumatoid arthritis

Nature Clinical Practice 2005; 1(1):31-9

McInnes IB,

Liew FY

This review describes cytokines and the cytokine network in chronic inflammatory diseases such as rheumatoid arthritis (RA). It also discusses how therapies that target cytokines may be feasible and efficacious treatments option for RA. Various targets are considered including blockade of tumour necrosis factor (TNF) and interleukin-1 (IL-1), as well as the targeting of cytokines that play a central role in immune regulation and tissue matrix destruction such as IL-6, IL-15, interferon-gamma (IF...

Keywords:

• JAK,
• MOA,
• Review

Cytokines in the pathogenesis of rheumatoid arthritis

Nature Reviews Immunology 2007; 7:429-42

McInnes IB,

Schett G

The imbalance between the activity of pro- and anti-inflammatory cytokines favouring induction of autoimmunity, chronic inflammation and joint damage is well known, but how cytokines are organised within a hierarchical regulatory network and which cytokines are the best targets for clinical intervention is uncertain. This review therefore examines the effector function of cytokines in the immunological processes central to the pathogenesis of rheumatoid arthritis (RA). The paper aims to try and ...

Keywords:

• JAK,
• Basic Science,
• MOA,
• Review

Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050

Journal of Immunology 2010; 184(9):5298-307

Fridman JS,

Scherle PA,

Collins R,

et al.

This preclinical characterisation study examined the efficacy and tolerability of the small molecule INCB028050 (now known as baricitinib), an orally bioavailable, selective Janus kinase (JAK) 1/JAK2 inhibitor, in rodent models of arthritis. The decision to investigate its effects of INCB028050 followed positive evidence for the related compound ruxolitinib, the JAK inhibitor tofacitinib and the IL-6 inhibitor tocilizumab in rheumatoid arthritis (RA). In this preclinical study, INCB028050 was sh...

Keywords:

• JAK,
• Baricitinib,
• Preclinical

Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)

Journal of Immunology 2011; 186(7):4234-43

Ghoreschi K,

Jesson MI,

Li X,

et al.

This study investigated the effects of the novel Janus kinase (JAK) inhibitor CP-690,550 (now known as tofacitinib) on adaptive and innate immune responses, in order to establish the mode of action of JAK inhibitors in the setting of inflammatory diseases. The inhibition of specific JAK/STAT-dependent pathways by CP-690,550 was determined through analysis of cytokine stimulation of mouse and human T cells in vitro.The effects of CP-690,550 on Th-cell differentiation of naive murine CD4+...

Keywords:

• JAK,
• Tofacitinib,
• Preclinical,
• Malignancy