Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis

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Authors
Martina Biggioggero MD, Andrea Becciolini MD, Chiara Crotti MD, Elena Agape MD, Ennio Giulio Favalli MD

Article Type
Review

DOI
10.7573/dic.212595

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint involvement, extra-articular manifestations, comorbidities, and increased mortality. In the last few decades, the management of RA has been dramatically improved by the introduction of a treat-to-target approach aiming to prevent joint damage progression. Moreover, the increasing knowledge about disease pathogenesis allowed the development of a new drug class of biologic agents targeted on immune cells and proinflammatory cytokines involved in RA network. Despite the introduction of several targeted drugs, a significant proportion of RA patients still fail to achieve the clinical target; so, more recently the focus of research has been shifted toward the inhibition of kinases involved in the transduction of the inflammatory signal into immune cells. In particular, two Janus kinase (JAK) inhibitors, baricitinib and tofacitinib, have been licensed for the treatment of RA as a consequence of a very favorable profile observed in randomized controlled trials (RCTs) conducted across different RA subpopulations. Both these new compounds are active on the majority of four JAK family members (JAK1, JAK2, JAK3, and TYK2), whereas the most recent emerging approach is directed toward the development of JAK1 selective inhibitors (upadacitinib and filgotinib) with the aim to improve the safety profile by minimizing the effects on JAK3 and, especially, JAK2. In this narrative review, we discuss the rationale for JAK inhibition in RA, with a special focus on the role of JAK1 selective blockade and a detailed description of available data from the results of clinical trials on upadacitinib and filgotinib.

Keywords: arthritis, filgotinib, Janus kinase 1, rheumatoid, upadacitinib.

Citation: Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG. Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis. Drugs in Context 2019; 8: 212595. DOI: 10.7573/dic.212595

Contributions: EGF designed the review methods and drafted and revised the paper. MB, CC, EA, and AB drafted and revised the paper. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: EGF served as a consultant and/or speaker for BMS, Eli-Lilly, Celgene, UCB, Pfizer, Novartis, and Sanofi-Genzyme. MB, CC, EA, and AB have declared no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at https://www.drugsincontext.com/wp-content/uploads/2019/10/dic.212595-COI.pdf

Acknowledgments: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2019 Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG. https://doi.org/10.7573/dic.212595. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2019 Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/upadacitinib-and-filgotinib:-the-role-of-jak1-selective-inhibition-in-the-treatment-of-rheumatoid-arthritis/

Correspondence: Ennio Giulio Favalli, Department of Rheumatology, Gaetano Pini Institute, Milan Via Gaetano Pini, 9, 20122 Milan, Italy. ennio.favalli@gmail.com

Provenance: invited; externally peer reviewed.

Submitted: 1 May 2019; Peer review comments to author: 1 July 2019; Revised manuscript received: 16 September 2019; Accepted: 17 September 2019; Publication date: 24 October 2019.

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