Selektif Bir JAK1 İnhibitörü Olan Filgotinib’in (GLPG0634), Faz IIB Doz Seçimi’ni Destekleyen, Farmakokinetik Özellikleri ve Farmakokinetik/Farmakodinamik Modellemesi
Clin Pharmacokinet. 2015 Feb 14. [Epub ahead of print]
Filgotinib (GLPG0634) is a selective inhibitor of JAK1 currently in development for the treatment of RA and Crohn’s disease. This paper describes the pharmacokinetics of filgotinib and its active metabolite, as well as the PK/PD modelling to support dose selection for phase IIB.
Two phase I, randomised, double-blind, placebo-controlled trials in healthy volunteers and one phase IIa proof-of-concept study in RA patients were used to evaluate single and multiple doses of filgotinib.
Two phase I, randomised, double-blind, placebo-controlled trials in healthy volunteers and one phase IIa proof-of-concept study in RA patients were used to evaluate single and multiple doses of filgotinib.
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İnflamatuar hastalıkların tedavisi için NLRP3 inflamazomunun küçük-moleküllü bir inhibitörü
Nat Med. 2015 Feb 16. doi: 10.1038/nm.3806. [Epub ahead of print]
A team of scientists at Trinity College Dublin and the University of Queensland Australia, led by Professor Luke O'Neill, have identified a key molecule that may result in the development of new anti-inflammatory therapies for diseases such as: cryopyrin-associated periodic syndrome (CAPS), multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis.
Professor O'Neill and his team have identified MCC950 as a potent, selective, small-molecule inhibitor of the NLRP3 infla...
Professor O'Neill and his team have identified MCC950 as a potent, selective, small-molecule inhibitor of the NLRP3 infla...
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January 2015
Romatoid Artritli Hastalarda Sağlıklı Gönüllülere Göre Anormal Lipid Profiline Neden Olan Potansiyel Mekanizmalar ve Bunların Tofacitinib Tarafından Tersine Çevrilmesi
Arthritis Rheumatol. 2015;67(3):616-25.
Active RA is associated with changes in both high- and low-density lipoprotein cholesterol as well as changes in the level and function of several HDL-associated proteins, yet the pathways and mechanisms involved with systemic inflammation altered lipid metabolism have not been determined. In addition, treatments for active RA are known to modify lipid metabolism, such as increasing circulating cholesterol levels. In the clinical development programme, a proportion of tofacitinib-treated patien...
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Aktif Romatoid Artritli Japon Hastalarda Tofacitinib’in Monoterapi Olarak Etkinliği ve Güvenliği: Bir 12-Haftalık, Randomize, Faz 2 Çalışma
Mod Rheumatol. 2014 Dec 11:1–25. [Epub ahead of print]
In Japan, the biologic DMARDs infliximab, etanercept, adalimumab, golimumab and certolizumab pegol, as well as tocilizumab and abatacept are approved for use in patients with active RA and an inadequate response to existing therapies. However, not all patients respond to these therapies adequately, creating an unmet need for therapeutic options with alternative mechanisms of action.
The oral JAK inhibitor tofacitinib has demonstrated efficacy as monotherapy or in combination with DMARDs ...
The oral JAK inhibitor tofacitinib has demonstrated efficacy as monotherapy or in combination with DMARDs ...
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Bir Oral JAK 1/2 İnhibitörü Olan Baricitinib’in Sağlıklı Gönüllülerde Farmakokinetik, Farmakodinamik ve Güvenliği
Mod J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.
Current biologic therapies for RA, such as biologic cytokine inhibitors, which selectively target inflammatory molecules with an exquisite degree of specificity, are not clinically effective in all patients with rheumatoid arthritis. As such, there remains an unmet clinical need for more effective and better tolerated therapies. Baricitinib (LY3009104, also previously known as INCB028050) is a potent and selective small molecule inhibitor of JAK1/2, which play an important role in cytokine signa...
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IL-6 Hasar sonrası İntestinal EpitelProliferasiyonu ve Tamirini Uyarır
PLoS One. 2014 Dec 5;9(12):e114195. doi: 10.1371/journal.pone.0114195. eCollection 2014.
IL-6 is an inflammatory cytokine known to contribute to a number of autoimmune diseases such as RA. Therapies targeting the soluble IL-6 receptor have now become effective treatments for RA. However, one unforeseen, yet rare, potential complication of anti-IL-6 therapy is bowel perforation. Yet within the intestine, IL-6 protects intestinal epithelial cells from apoptosis during prolonged inflammation.
The authors hypothesized that IL-6 may have beneficial properties in wound response/rep...
The authors hypothesized that IL-6 may have beneficial properties in wound response/rep...
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December 2014
Metotreksata yetersiz yanıt veren romatoid artritli hastalarda baricitinibin 24 haftadaki güvenlik ve etkinliği
Ann Rheum Dis. 2015;74(2):333–340
Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies.
This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...
This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...
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JAK-STAT yolunun romatoid artritteki aktivitesi: STAT3’ün konstitütif aktivasyonu interlökin 6 seviyeleri ile ilişkilidir.
Rheumatology (Oxford). 2014 Nov 17. pii: keu430. [Epub ahead of print]
Non-response, parenteral administration and cost to produce are all aspects associated with the currently available anti-cytokine agents for RA. These related factors mean that alternative drugs are now being developed. Recent developments in therapeutic drugs to treat RA have focused on Janus kinases (JAKs) and signal transducer and activator of transcription (STATs) transcription pathways. Several cytokines that regulate immune responses in RA, such as IFN-g, IL-6 and IL-10, activate JAK-STAT ...
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JAK inhibitörü tofacitinib romatoid artritte sinovyal JAK1-STAT sinyalizasyonunu baskılar
Ann Rheum Dis. 2014 Nov 14. pii: annrheumdis-2014-206028. doi: 10.1136/annrheumdis-2014-206028. [Epub ahead of print]
Targeting intracellular pathways such as JAK/STAT represents a novel approach to the treatment of RA. Tofacitinib is an oral JAK inhibitor, proven to be effective in the treatment of RA, yet the pathways affected by tofacitinib and the effects on gene expression in situ are unknown. In this study, Boyle et al. tested the hypothesis that tofacitinib targets cytokine signalling critical to the pathogenesis of rheumatoid synovitis by investigating tofacitinib effects on synovial pathobiology.
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Randomize klinik çalışmalarda biyolojik ilaçlar ve tofacitinib ile tedavi edilen kronik inflamatuar artritli hastalardaki lipid profili değişiklikleri: Bir sistematik derleme ve meta analiz
Arthritis Rheumatol. 2015;67(1):117–127
Systemic inflammation, reflected by high levels of C-reactive protein and the erythrocyte sedimentation rate, has been identified as an independent risk factor for cardiovascular disease, the most important cause of death in RA and SpA. Studies with TNF antagonists have given contradictory results on cardiovascular risk. As such, this systemic literature search aimed to analyse lipid changes in RA and SpA subjects treated with biologics or tofacitinib in randomized clinical trials.
The s...
The s...