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Joint Bone Spine
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le samedi 12 octobre 2019
Doi : 10.1016/j.jbspin.2019.09.005
accepted : 4 September 2019
Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum

Thomas El Jammal, Mathieu Gerfaud-Valentin, Pascal Sève, Yvan Jamilloux
 Department of Internal Medicine, Lyon University Hospital, 69004 Lyon, France 

Corresponding author at: Service de Médecine Interne, Groupement Hospitalier Nord, 103, grande rue de la Croix-Rousse, 69004 Lyon, France.Service de Médecine Interne, Groupement Hospitalier Nord103, grande rue de la Croix-RousseLyon69004France

Three Janus kinase (JAK) inhibitors, ruxolitinib, tofacitinib, and baricitinib, are currently approved by the FDA/EMA for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative rectocolitis. The inhibition of JAK/STAT signaling by these small molecules, downstream of several cytokine receptors, results in lower pro-inflammatory gene expression. Given the cytokine profiles observed in rheumatologic diseases, most of the recent therapeutic strategies target cytokines, either directly or through their receptors. Each cytokine receptor recruits a specific combination of JAKs to activate different programs in cells. The approved drugs are panJAK inhibitors, able to impede more than one pathway. These drugs are being tested in various rheumatologic disorders. At the same time, more specific molecules able to target one specific JAK are being developed. In this review, we describe the expanding spectrum of rheumatologic and autoimmune conditions for which JAK inhibition may represent new avenues in clinical practice.

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Keywords : JAK inhibitor, Rheumatology, Rheumatoid arthritis, Psoriatic arthritis, Tofacitinib

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