TY - JOUR T1 - RMD commentary, JAK kinase inhibitors: a preferred alternative to TNF inhibitors? JF - RMD Open JO - RMD Open DO - 10.1136/rmdopen-2021-001565 VL - 7 IS - 1 SP - e001565 AU - Vibeke Strand Y1 - 2021/02/01 UR - http://rmdopen.bmj.com/content/7/1/e001565.abstract N2 - The JAK kinase inhibitors (JAKis) represent an exciting class of therapies in rheumatology, and they are effective across a wide variety of immune-mediated diseases, in haematology (myelofibrosis, polycythemia vera and acute graft-versus-host disease), dermatology and gastroenterology (ulcerative colitis), interferonopathies, sarcoidosis and recently COVID-19 (baricitinib). Their use in rheumatoid arthritis (RA) has convincingly demonstrated an early onset of benefit and anecdotally, better adherence. In a combined analyses of the phase III RA randomised controlled trials (RCTs) and long-term extensions (LTE) with tofacitinib, approximately 78% remained on therapy at 2 years and 51% at 5 years.1 Orally administered, they are convenient and easy to use, without concerns regarding immunogenicity. And they have the shortest half-lives of all of our therapeutic classes.It is interesting that the approved JAKis demonstrate different selectivity profiles in vitro, modulating distinct cytokine signalling pathways to different degrees and duration. Yet, they do not potently or continuously inhibit any individual cytokine pathway over 24 hours.2 It is unclear which cell types and which signalling pathways are affected at any given time or for how long. Despite different selectivities, clinical responses are similar, especially across agents in RA, psoriatic arthritis (PsA) and spondyloarthritis (SpA). Four are EMA approved in RA (tofacitinib, baricitinib, upadacitinib and filgotinib), 3 by FDA (except filgotonib); tofacitinib in polyarticular JIA; tofacitinib in PsA with upadacitinib expected, as are tofacitinib and upadacitinib expected in SpA. Indications of efficacy based on open-label series or early trials are evident in systemic lupus erythematosus, dermatomyositis, systemic sclerosis, Sjogren’s syndrome and non-infectious uveitis.Perhaps even more compelling are the uniformly strong data available with all the JAKis studied in methotrexate incomplete responder (MTX-IR) patients with RA, resulting in clinically meaningful improvements (≥minimum clinically important differences (MCID)) across all patient-reported outcomes (PROs): patient global assessment of disease activity (PtGA), … ER -