FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3164401096> ?p ?o ?g. }

• W3164401096 endingPage "1151" @default.
• W3164401096 startingPage "1150.2" @default.
• W3164401096 abstract "Background: Cytokines are important mediators of inflammation and tissue destruction in rheumatoid arthritis (RA) 1 . Several cytokines involved in RA pathogenesis act through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway 2 . The effects of JAK-inhibitor tofacitinib on cytokine signaling in vitro are well established, while in vivo evidence in patients remains scarce. Objectives: To investigate in vivo in rheumatoid arthritis patients i) which JAK-STAT pathways are inhibited by tofacitinib and ii) if baseline signaling profile is associated with the treatment response. Methods: Sixteen patients with active RA, despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), received tofacitinib 5 mg twice daily for three months. Levels of basal and cytokine-induced phosphorylated STATs and total STAT1 and STAT3 in peripheral blood monocytes, T cells and B cells were measured by flow cytometry. mRNA expression of JAKs, STATs and suppressors of cytokine signaling (SOCS) were measured from peripheral blood mononuclear cells (PBMCs) by quantitative PCR. Association of baseline signaling profile with treatment response (the change from baseline in disease activity score (DAS28)) was studied by calculating correlation coefficients. Results: Treatment with tofacitinib and csDMARDs decreased median DAS28 from 4.4 to 2.6 (p < 0.001). Tofacitinib significantly decreased cytokine-induced phosphorylation of all JAK-STAT pathways studied. Basal STAT1, STAT3, STAT4 and STAT5 phosphorylation in monocytes and/or T cells was downregulated by tofacitinib. No changes were observed in STAT1 and STAT3 protein levels, while gene expression of STAT3 , STAT4 , STAT5A , JAK1 , JAK3 and all studied SOCS s was significantly suppressed. Baseline STAT phosphorylation levels in T cells and monocytes and SOCS3 expression in PBMCs correlated with treatment response. Conclusion: Tofacitinib suppresses multiple JAK-STAT pathways in RA patients in vivo . Baseline JAK-STAT signaling profile may be applicable as a prognostic marker for treatment response to tofacitinib. References: [1]McInnes, I. B., Buckley, C. D. & Isaacs, J. D. Cytokines in rheumatoid arthritis-shaping the immunological landscape. Nature Reviews Rheumatology vol. 12 63–68 (2016). [2]Schwartz, D. M., Bonelli, M., Gadina, M. & O’Shea, J. J. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat. Rev. Rheumatol. 12 , 25–36 (2016). Acknowledgements: This study was supported by Pfizer Inc. Disclosure of Interests: Maaria Palmroth Consultant of: Pfizer and from 1/21 a part-time employee of MedEngine and consultant for Pfizer, Krista Kuuliala Grant/research support from: Pfizer, Ritva Peltomaa Speakers bureau: Boehringer Ingelmheim, Pfizer, Sanofi, Paid instructor for: Boehringer Ingelheim, Eli Lilly and Company, Janssen, Abbvie, UCB Pharma, Anniina Virtanen: None declared, Antti Kuuliala: None declared, Antti Kurttila: None declared, Anna Kinnunen: None declared, Marjatta Leirisalo-Repo: None declared, Olli Silvennoinen Speakers bureau: Pfizer, AbbVie, Pia Isomäki Speakers bureau: Abbvie, Eli Lilly and Company, Pfizer, Roche, Paid instructor for: Abbvie, Eli Lilly and Company, Pfizer, Roche, Grant/research support from: Pfizer" @default.
• W3164401096 created "2021-06-07" @default.
• W3164401096 creator A5006623618 @default.
• W3164401096 creator A5014117301 @default.
• W3164401096 creator A5014350310 @default.
• W3164401096 creator A5024144901 @default.
• W3164401096 creator A5029039417 @default.
• W3164401096 creator A5034562303 @default.
• W3164401096 creator A5042453652 @default.
• W3164401096 creator A5057213310 @default.
• W3164401096 creator A5067508775 @default.
• W3164401096 creator A5083669558 @default.
• W3164401096 date "2021-05-19" @default.
• W3164401096 modified "2023-09-27" @default.
• W3164401096 title "AB0250 TOFACITINIB SUPPRESSES SEVERAL JAK-STAT PATHWAYS IN RHEUMATOID ARTHRITIS AND BASELINE SIGNALING PROFILE ASSOCIATES WITH TREATMENT RESPONSE" @default.
• W3164401096 doi "https://doi.org/10.1136/annrheumdis-2021-eular.448" @default.
• W3164401096 hasPublicationYear "2021" @default.
• W3164401096 type Work @default.
• W3164401096 sameAs 3164401096 @default.
• W3164401096 citedByCount "0" @default.
• W3164401096 crossrefType "journal-article" @default.
• W3164401096 hasAuthorship W3164401096A5006623618 @default.
• W3164401096 hasAuthorship W3164401096A5014117301 @default.
• W3164401096 hasAuthorship W3164401096A5014350310 @default.
• W3164401096 hasAuthorship W3164401096A5024144901 @default.
• W3164401096 hasAuthorship W3164401096A5029039417 @default.
• W3164401096 hasAuthorship W3164401096A5034562303 @default.
• W3164401096 hasAuthorship W3164401096A5042453652 @default.
• W3164401096 hasAuthorship W3164401096A5057213310 @default.
• W3164401096 hasAuthorship W3164401096A5067508775 @default.
• W3164401096 hasAuthorship W3164401096A5083669558 @default.
• W3164401096 hasBestOaLocation W31644010961 @default.
• W3164401096 hasConcept C112392421 @default.
• W3164401096 hasConcept C126322002 @default.
• W3164401096 hasConcept C157333092 @default.
• W3164401096 hasConcept C170493617 @default.
• W3164401096 hasConcept C171958077 @default.
• W3164401096 hasConcept C203014093 @default.
• W3164401096 hasConcept C2775855021 @default.
• W3164401096 hasConcept C2776112149 @default.
• W3164401096 hasConcept C2777575956 @default.
• W3164401096 hasConcept C2778277574 @default.
• W3164401096 hasConcept C2778690821 @default.
• W3164401096 hasConcept C2778886723 @default.
• W3164401096 hasConcept C2778923194 @default.
• W3164401096 hasConcept C2779391668 @default.
• W3164401096 hasConcept C2780007613 @default.
• W3164401096 hasConcept C2780076729 @default.
• W3164401096 hasConcept C42362537 @default.
• W3164401096 hasConcept C502942594 @default.
• W3164401096 hasConcept C62478195 @default.
• W3164401096 hasConcept C65439459 @default.
• W3164401096 hasConcept C71924100 @default.
• W3164401096 hasConcept C86803240 @default.
• W3164401096 hasConcept C95444343 @default.
• W3164401096 hasConcept C98274493 @default.
• W3164401096 hasConceptScore W3164401096C112392421 @default.
• W3164401096 hasConceptScore W3164401096C126322002 @default.
• W3164401096 hasConceptScore W3164401096C157333092 @default.
• W3164401096 hasConceptScore W3164401096C170493617 @default.
• W3164401096 hasConceptScore W3164401096C171958077 @default.
• W3164401096 hasConceptScore W3164401096C203014093 @default.
• W3164401096 hasConceptScore W3164401096C2775855021 @default.
• W3164401096 hasConceptScore W3164401096C2776112149 @default.
• W3164401096 hasConceptScore W3164401096C2777575956 @default.
• W3164401096 hasConceptScore W3164401096C2778277574 @default.
• W3164401096 hasConceptScore W3164401096C2778690821 @default.
• W3164401096 hasConceptScore W3164401096C2778886723 @default.
• W3164401096 hasConceptScore W3164401096C2778923194 @default.
• W3164401096 hasConceptScore W3164401096C2779391668 @default.
• W3164401096 hasConceptScore W3164401096C2780007613 @default.
• W3164401096 hasConceptScore W3164401096C2780076729 @default.
• W3164401096 hasConceptScore W3164401096C42362537 @default.
• W3164401096 hasConceptScore W3164401096C502942594 @default.
• W3164401096 hasConceptScore W3164401096C62478195 @default.
• W3164401096 hasConceptScore W3164401096C65439459 @default.
• W3164401096 hasConceptScore W3164401096C71924100 @default.
• W3164401096 hasConceptScore W3164401096C86803240 @default.
• W3164401096 hasConceptScore W3164401096C95444343 @default.
• W3164401096 hasConceptScore W3164401096C98274493 @default.
• W3164401096 hasIssue "Suppl 1" @default.
• W3164401096 hasLocation W31644010961 @default.
• W3164401096 hasOpenAccess W3164401096 @default.
• W3164401096 hasPrimaryLocation W31644010961 @default.
• W3164401096 hasRelatedWork W1527527757 @default.
• W3164401096 hasRelatedWork W2164716517 @default.
• W3164401096 hasRelatedWork W2188045930 @default.
• W3164401096 hasRelatedWork W2916246606 @default.
• W3164401096 hasRelatedWork W3029773958 @default.
• W3164401096 hasRelatedWork W3164401096 @default.
• W3164401096 hasRelatedWork W3195533486 @default.
• W3164401096 hasRelatedWork W3204231006 @default.
• W3164401096 hasRelatedWork W3216146155 @default.
• W3164401096 hasRelatedWork W4210803037 @default.
• W3164401096 hasVolume "80" @default.
• W3164401096 isParatext "false" @default.
• W3164401096 isRetracted "false" @default.
• W3164401096 magId "3164401096" @default.

• next