July 2024

The association between genetics and response to treatment with biologics in patients with psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel diseases: A systematic review and meta-analysis

Journal Reference: Int J Mol Sci 2024;25:5793 doi: 10.3390/ijms25115793

Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes were associated with a response to TNFi, when assessing several inflammatory diseases together. Al-Sofi et al. conducted a systematic review and meta-analysis on single nucleotide polymorphism (SNP) genetic markers and their response to biologics in psoriasis, PsA, RA, IBD, and across all chronic inflammatory diseases together.

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February 2024

Modulation of IL-23 Signalling with Guselkumab in Biologic-Naïve Patients Versus TNF Inhibitor-Inadequate Responders with Active Psoriatic Arthritis

Arthritis Rheumatol 2024 doi 10.1002/art.42803 Epub ahead of print

Guselkumab treatment exhibited generally comparable and significant pharmacodynamic effects on IL-23/Th17–associated cytokines across participants with PsA who are biologic-naïve or have TNFi-IR. In coming to this conclusion, investigators assessed and compared immunologic differences and associations with clinical response to guselkumab in participants with active PsA who were biologic-naïve or TNFi-IR.

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September 2023

Differential Properties of Janus Kinase Inhibitors in the Treatment of Immune-mediated Inflammatory Diseases

Rheumatology (Oxford) 2023;63(2):298–308 doi 10.1093/rheumatology/kead448

JAKis differ in structure, which affects their inhibitory concentration for different JAKs.

This review by Taylor, et al. compares the pharmacological profiles of JAKis, including abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib, and upadacitinib.

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Guselkumab Modulates Differentially Expressed Genes in Blood of Patients with Psoriatic Arthritis: Results from Two Phase 3, Randomized, Placebo-Controlled Trials

ACR Open Rheumatol. 2023 doi: 10.1002/acr2.11589

Whole blood transcriptome profiling reveals differential gene expression in patients with active PsA from the DISCOVER-1 and DISCOVER-2 clinical studies in comparison with healthy controls.

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June 2022

Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications

Rheumatol Ther 2022 Jun;9(3):935-955. Doi: 10.1007/s40744-022-00434-z

Merola et al., reported the effect of interleukin (IL)-17A inhibition with secukinumab on cardiovascular (CV) risk parameters in patients with psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) over 1 year of treatment. This study evaluated data from 19 secukinumab related clinical trials in phase 3/4 in psoriasis, PsA, and axSpA.

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Effects of anti-TNF-therapy on inflammatory, structural and osteoblastic activity lesions in radiographic axial spondyloarthritis - a prospective proof-of-concept study using PET/MRI of SIJ and spine

Arthritis Rheumatol. 2022 doi: 10.1002/art.42149

Bruckmann et al carried out this observational, proof of concept study to analyse the effect anti-TNF-therapy (TNFi) on inflammatory, structural, and osteoblastic activity lesions in radiographic axial spondyloarthritis (r-axSpA).  

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February 2022

Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach

Nat Rev Rheumatol. 2022 Jan 5:1–13. Epub ahead of print doi: 10.1038/s41584-021-00726-8

The development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders, to the extent that they could ultimately enable either complete withdrawal or avoidance of glucocorticoid use in some autoimmune diseases, and could have the potential to regulate any active factor inhibiting the transition to cure.In this review paper, Tanaka, et al. describe the progress in JAK-targetin...

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November 2021

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.

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...

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June 2021

JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic arthritis

Clin Exp Rheumatol. 2021;39(3):668-675.

The JAK/STAT pathway is receiving increasing attention in modulation of nociceptive responses, given its clear role in cytokine signalling. The authors of this review speculate that JAKinibs may have an effect on the modulation of nociception and reduction of pain.Crispino N, et al. review the impact of pain in patients with rheumatic disease and the physiological basis of modulating nociceptive pain. They examine the role of cytokines in the modulation of pain and analyse current clinical JAKin...

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April 2021

JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib

Ann Rheum Dis. 2021 Mar 19:annrheumdis-2020-219012. Epub ahead of print. DOI: 10.1136/annrheumdis-2020-219012

The first study to combine in vitro inhibition of cytokine responses in whole blood with clinical pharmacokinetics of individual JAKinibs to model daily cytokine-mediated pharmacodynamic profiles in healthy individuals and patients with RA, has demonstrated that JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type.Traves and colleagues have observed that JAKinibs have unique, differential effects on specific cytokine signalling pathways, dependent on cytokine stimulus, ST...

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