2020
DOI: 10.1007/s40265-020-01349-1
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Selectivity of Janus Kinase Inhibitors in Rheumatoid Arthritis and Other Immune-Mediated Inflammatory Diseases: Is Expectation the Root of All Headache?

Abstract: Janus kinase (JAK) is a signal transducer and activator of a protein transcription system that transduces signals from cell surface cytokine and growth factor receptors to the nucleus. Recently developed JAK inhibitors (JAKinibs) inhibit JAKs non-selectively or selectively and down-regulate the effects of corresponding ligands (i.e. cytokines and growth factors). JAKinibs are efficacious against rheumatoid arthritis and other immune-mediated inflammatory diseases and are being increasingly prescribed clinicall… Show more

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Cited by 41 publications
(19 citation statements)
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References 87 publications
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“…Although efficacy of JAK1 inhibition is clear, safety of long-term JAK1 inhibition in the AD population has not yet been established. To date, JAK inhibitor safety was primarily established in patients with rheumatoid arthritis (RA) [ 13 , 14 ]. JAK inhibition in RA is associated with risk of infections (including viral reactivation and opportunistic infections), malignancy, nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and various changes in hematologic parameters [ 13 , 14 ].…”
Section: Introductionmentioning
confidence: 99%
“…Although efficacy of JAK1 inhibition is clear, safety of long-term JAK1 inhibition in the AD population has not yet been established. To date, JAK inhibitor safety was primarily established in patients with rheumatoid arthritis (RA) [ 13 , 14 ]. JAK inhibition in RA is associated with risk of infections (including viral reactivation and opportunistic infections), malignancy, nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and various changes in hematologic parameters [ 13 , 14 ].…”
Section: Introductionmentioning
confidence: 99%
“…21 Although HZV reactivation appears to be a class effect, some emerging data suggest that there may be relative differences among the various JAK inhibitors regarding the risk of HZV. 22,23 However, additional data (e.g., from head-to-head studies) are needed to draw any conclusions regarding potential differences in the risk of HZV infection between filgotinib and other JAK inhibitors.…”
Section: Discussionmentioning
confidence: 99%
“…Indirect comparisons using systematic reviews and meta-analyses suggest that all four approved JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) are effective options in the management of RA with inadequate responses to csDMARDs or bDMARDs, although there are some differences in their efficacy and tolerability profiles [ 24 27 ]. The risk of infection appears to be similar among approved JAK inhibitors, although herpes zoster infections may be less frequent with filgotinib [ 28 30 ]. Longer-term and real-world efficacy and safety data and cost-effectiveness analyses will be useful in further positioning filgotinib relative to other treatment options (including JAK inhibitors) in these patients.…”
Section: What Is the Current Clinical Position Of Filgotinib In Ra?mentioning
confidence: 99%