Place des inhibiteurs de JAK dans le traitement de la polyarthrite rhumatoïde

Abstract

Kinases are enzymes in charge of phosphorylation in cellular activation pathways. Kinase inhibitors are already used to treat cancer and in recent years, many studies have been conducted to develop kinase inhibitors in autoimmune diseases. Janus kinases (JAK) are the most studied and JAK inhibitors (tofacitinib and baricitinib) have been studied in phase III trials in rheumatoid arthritis. Many studies have been conducted and different therapeutic scenarios have been studied. JAK inhibitors were studied in association to méthotrexate in case of incomplete response to méthotrexate alone, in association to méthotrexate in case of incomplete response to anti-tumor necrosis factor (TNF) α. A step-down strategy in case of good response to JAK inhibitors has also been studied. Infections are the most described side effect. Cancer risk seems to be the same with JAK inhibitors and biological disease-modifying antirheumatic drugs (DMARDs), but a longer time of exposure and real life studies are mandatory to be reassured. JAK inhibitors have several advantages, mainly the oral administration possibly once daily, a short half-life, efficacy, hopefully a production cost smaller than biological DMARDs and no immunogenicity. Evidence-based data allow us to use JAK inhibitors at any stage of rheumatoid arthritis evolution but the product positioning will be determined by their price. EULAR recommended using JAK inhibitors in case of insufficient response to conventional or biological DMARD.