Upadacitinib in rheumatoid arthritis: a profile of its use
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ADIS DRUG Q&A
Upadacitinib in rheumatoid arthritis: a profile of its use Sean Duggan1 · Susan J. Keam1 Published online: 26 October 2020 © Springer Nature Switzerland AG 2020
Abstract Upadacitinib (Rinvoq™), an oral Janus kinase (JAK) 1 inhibitor, is approved as monotherapy or in combination with nonbiological disease-modifying antirheumatic drugs (DMARDs), including methotrexate, in adult patients with moderate to severely active rheumatoid arthritis (RA) who have responded inadequately to, or who are intolerant to one or more DMARD. Across phase 3 trials in patients with RA, once-daily upadacitinib treatment was generally well tolerated and associated with rapid and clinically relevant disease remission or low disease activity when administered as monotherapy or in combination conventional synthetic DMARDs (csDMARDs), including in patients who were intolerant to or had an inadequate response to prior csDMARDs or biological DMARD (bDMARD) therapy. In addition, in head-to-head trials, upadacitinib was more effective than both adalimumab in patients with an inadequate response to methotrexate and abatacept in patients with an inadequate response to or intolerance to bDMARDs. The clinical benefits of upadacitinib, including slowing progression of joint damage, were maintained over the longer term and no new safety signals were identified.
Adis evaluation of upadacitinib in RA Second-generation JAK inhibitor with greater selectivity for JAK1 than JAK2 or JAK3 Convenient once-daily oral formulation As monotherapy or combination therapy, provides rapid and sustained improvements in RA signs and symptoms, disease activity, and slows progression of structural joint damage More effective than adalimumab and abatacept overall in terms of improvements in disease activity and remission rates Generally well tolerated during up to 3 years’ treatment
Enhanced material for this Adis Drug Q&A can be found at https ://doi.org/10.6084/m9.figshare.12971927. * Sean Duggan [email protected] 1
Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand
What is the rationale for developing upadacitinib? The recent emergence of biological disease-modifying antirheumatic drugs (bDMARDS) such as tumour necrosis factor (TNF)-α antagonists (e.g. adalimumab), interleukin (IL)-6 inhibitors (e.g. tocilizumab), and B- and T-cell targeted therapies (e.g. rituximab and abatacept) has offered alternative options for patients with rheumatoid arthritis (RA), particularly in patients with inadequate responses to methotrexate and other conventional synthetic DMARDS (csDMARDs). However, bDMARDs also have some limitations, such as patients not always achieving therapeutic targets [1] and inconvenient administration regimens (i.e. subcutaneous or intravenous), indicating an unmet need for additional therapies. This has led to the development of novel agents that target alternative pathogenic pathways in RA, with recent focus placed on Janus kinase (JAK) inhibitors. Inhibition of JAK results in modulation of JAK-mediated signa
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