Publications

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

Al-Sofi RF,

Bergmann MS,

Nielsen CH,

Andersen V,

Skov L,

Loft N

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.

Keywords:

• Basic Science,
• Switching,
• TNF

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

Siebert S,

Coates LC,

Schett G,

Raychaudhuri SP,

Chen W,

Gao S,

Seridi L,

Chakravarty SD,

Shawi M,

Lavie F,

Sharaf M,

Zimmermann M,

Kollmeier AP,

Xu XL,

Rahman P,

Mease PJ,

Deodhar A

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.

Keywords:

• Basic Science,
• Guselkumab

乾癬性関節患者においてグセルクマブは発現変動遺伝子を修飾する: 2つの無作為化プラセボ対照フェーズ3試験からの解析

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

Siebert S,

Sweet KM,

Ritchlin CT,

Hsia EC,

Kollmeier AP,

Xu XL,

Seridi L,

Song Q,

Gao S,

Chen W,

Miron M

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.

Keywords:

• IL-23,
• Guselkumab,
• Phase 3,
• Basic Science,
• MOA

免疫介在性炎症疾患におけるヤヌスキナーゼ阻害薬の相違

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

Taylor PC,

Choy E,

Baraliakos X,

Szekanecz Z,

Xavier RM,

Isaacs JD,

Strengholt S,

Parmentier JM,

Lippe R,

Tanaka Y

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.

Keywords:

• JAK,
• Basic Science,
• MOA

TNFI阻害薬の体軸性脊椎関節炎の炎症、構造および骨増殖性病変に対する効果 – SIJと脊椎のPET/MRIを　用いた前向きPOC試験

Arthritis Rheumatol. 2022 doi: 10.1002/art.42149

Bruckmann NM,

Rischpler C,

Tsiami S,

Kirchner J,

Abrar DB,

Bartel T,

Theysohn J,

Umutlu L,

Herrmann K,

Fendler WP,

Buchbender C,

Antoch G,

Sawicki LM,

Tsobanelis A,

Braun J,

Baraliakos X

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).  

Keywords:

• TNF,
• Basic Science,
• Bone,
• Radiographic

心血管イベントリスクと炎症性バイオマーカーに対する セクキヌマブの影響: 3つの適用疾患における統合データ

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

Merola JF,

McInnes IB,

Deodhar AA,

Dey AK,

Adamstein NH,

Quebe-Fehling E,

Aassi M,

Peine M,

Mehta NN

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.

Keywords:

• IL-17,
• Secukinumab,
• Basic Science,
• Biomarkers

ヤヌスキナーゼを標的としたリウマチ性疾患治療: メカニズムに基づいたアプローチ

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

Tanaka Y,

Luo Y,

O'Shea JJ,

Nakayamada S

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...

Keywords:

• JAK,
• Basic Science

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

関節リウマチと乾癬性関節炎におけるJAK/STAT 経路と侵害受容サイトカインシグナル

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

Crispino N,

Ciccia F.

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...

Keywords:

• JAK,
• Basic Science,
• MOA

filgotinib, upadacitinib, tofacitinib, baricitinibのJAK選択性とる薬動力学的サイトカインシグナル抑制

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

Traves PG,

Murray B,

Campigotto F,

Galien R,

Meng A,

Di Paolo JA

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...

Keywords:

• JAK,
• Basic Science,
• MOA