2020
DOI: 10.3389/fimmu.2020.591176
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Impact of Janus Kinase Inhibition on the Treatment of Axial Spondyloarthropathies

Abstract: Many immune cells and effector molecules (e.g. cytokines, Interferons, growth factors) utilize different combinations of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules to transduce signals from the cell surface to the nucleus, where they regulate transcription. This pathway is basically involved in almost all inflammatory diseases and also in the interleukin (IL)-23/IL-17 cascade, which is an essential part of the pathogenesis of spondyloarthropathies (SpA). Upon evide… Show more

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Cited by 18 publications
(9 citation statements)
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“…In clinical trials, the safety profile of the evaluated JAKi was good, with data consistent with results obtained during phase-three trials in RA. Adverse events of interest in patients with axSpA receiving JAKi include infections (especially herpes zoster); venous thromboembolism; and specific laboratory abnormalities, such as elevated CPK or lipid parameters [ 25 ]. Concerns have recently emerged regarding the risk of thrombosis under tofacitinib, leading to warnings by the competent authorities.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In clinical trials, the safety profile of the evaluated JAKi was good, with data consistent with results obtained during phase-three trials in RA. Adverse events of interest in patients with axSpA receiving JAKi include infections (especially herpes zoster); venous thromboembolism; and specific laboratory abnormalities, such as elevated CPK or lipid parameters [ 25 ]. Concerns have recently emerged regarding the risk of thrombosis under tofacitinib, leading to warnings by the competent authorities.…”
Section: Discussionmentioning
confidence: 99%
“…Of interest, TNFα, a key cytokine driving inflammation in axSpA, does not use the JAK/STAT pathway. However, inhibition of JAK2/TYK2 or JAK1/JAK2 modulates its production by the inhibition of IL-12 and IFNγ production [ 23 , 24 , 25 ]. Genetic studies have identified polymorphisms in JAK2 and STAT3 as susceptibility factors for AS [ 26 ].…”
Section: The Implication Of the Jak/stat Pathway In Spondyloarthritismentioning
confidence: 99%
“…JAK inhibitors bind to and modulate the intracellular activity of JAKs. With regard to AS, JAKs are involved in the IL-23/IL-17 pathway, and IL-17A production is mainly JAK-2 dependent ( 18 ). The benefits of JAK inhibitors (tofacitinib, upadacitinib, and filgotinib) in AS have been shown in clinical trials ( 19 ).…”
Section: Discussionmentioning
confidence: 99%
“…Besides directly IL-6 targeting agents, Janus kinase inhibitors reduce IL-6 signaling, and they may have impressive SAA-reducing effects in RA but none of the available drugs (tofacitinib, baricitinib, upadacitinib, and filgotinib) have consistently been evaluated in renal amyloidosis ( 35 ). However, of notice, upadacitinib is now licensed for the use in AS and renal impairment has a limited effect on upadacitinib pharmacokinetics ( 36 , 37 ).…”
Section: Discussionmentioning
confidence: 99%