Relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison to adalimumab in pa
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Rheumatologie Originalien Z Rheumatol https://doi.org/10.1007/s00393-020-00750-1 © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020 Redaktion U. Müller-Ladner, Bad Nauheim U. Lange, Bad Nauheim
Introduction Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovial joint inflammation, which leads to disability and reduced quality of life [1]. Methotrexate (MTX), an effective disease-modifying antirheumatic drug (DMARD) [2], is one of the most widely used DMARDs for the treatment of RA [3]. However, not all patients are responsive to the drug and 30% of patients discontinue therapy within 1 year of commencing treatment, usually because of a lack of efficacy or undesirable adverse effects [4]. Tumor necrosis factor (TNF) antagonists, such as adalimumab, are among the most effective therapies for RA, but a substantial proportion of patients do not respond adequately to these therapies [5]. The intracellular pathways, which include the Janus kinases (JAKs–JAK1, JAK2, JAK3) and tyrosine kinase 2 (Tyk2), are critical to immune cell activation, pro-inflammatory cytokine production, and cytokine signaling [6]. Small-molecule JAK inhibitors have been clinically developed for the treatment of RA [7]. Tofacitinib is an orally administered JAK inhibitor [8]. It selectively inhibits JAK-1, JAK-2, and JAK-3, with a functional cellular specificity for JAK-1 and JAK-3 over JAK-2 [9, 10]. Barici-
Young Ho Lee · Gwan Gyu Song Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seongbuk-gu, Seoul, Korea (Republic of)
Relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison to adalimumab in patients with active rheumatoid arthritis tinib is a potent selective JAK1 and JAK2 inhibitor [11]. Baricitinib shows similar inhibitory activities against both JAK1 and JAK2, but reduced activities against JAK3 and tyrosine kinase 2 [12]. To date, tofacitinib (JAK1/JAK3, JAK2 inhibitor) and baricitinib (JAK1 and JAK2 inhibitor) are the only approved JAK inhibitors and may be used as a treatment for RA either alone or in combination with MTX [13, 14]. Upadacitinib and filgotinib, new JAK inhibitors, have been engineered to confer greater selectivity for JAK1 than for JAK2, JAK3, and Tyk2 [15]. Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in patients with active RA with an incomplete response to MTX. All these drugs have shown considerable efficacy in placebo-controlled trials, but the relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib remain unclear due to a lack of data from head-to-head comparison trials [16–19]. In the absence of head-tohead trials of the relevant comparators, it is necessary to combine evidence from randomized controlled trials (RCTs) of different treatments to derive an estimate of the effect of one treatment as compared to that of the other [20
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