Early phase studies of JAK1 selective inhibitors in rheumatoid arthritis

Abstract

Abstract The first approved Janus kinase (JAK) inhibitors for treatment of RA targeted more than one JAK molecule. Although this brings an advantage of simultaneous blocking of more cytokines involved in RA, it may also carry an increased risk of toxicity. Subsequently, more selective JAK inhibitors were developed with the aim of improving the safety–efficacy profile and to further increase drug maintenance. With this proposal, early phase trials of selective JAK1 inhibitors, namely upadacitinib, filgotinib and itacitinib, were initiated in recent years to identify the efficacy and adverse effects of these agents and to define their potential role in treatment of inflammatory and autoimmune diseases. Early phase (Phase I–II) studies of upadacitinib and filgotinib provided evidence for efficacy and safety of the selective JAK1 inhibitors in refractory populations of RA patients and allowed informed selection of the appropriate dose by balancing the optimal benefit–risk profile for further evaluation in the later successfully performed Phase III trials. Although itacitinib also demonstrated a good efficacy and safety in a Phase II trial in RA patients, it is mainly in development for haematologic and oncologic conditions. CME: This supplement is CME Accredited. To receive a CME certificate of participation, you should:  Read all the papers in the supplement Register or log in at www.paradigmmc.com/962 to complete and submit the post activity assessment. You must answer 70% of the questions correctly to earn credit. You will have unlimited opportunities to successfully complete the assessment. You will receive a maximum of 7.0 AMA PRA Category 1 CreditsTM upon successful completion of the assessment.