JANUS KINASE ENZYME (JAK) INHIBITORS AND RHEUMATOID ARTHRITIS: A REVIEW OF THE LITERATURE
DOI:
https://doi.org/10.22159/ijcpr.2019v11i6.36343Keywords:
Cytokines, Janus Kinase Enzyme Inhibitors, JAKinibs, Rheumatoid ArthritisAbstract
Cytokines play an essential role in normal cell growth and the regulation of immune function. The emergence of Janus Kinase Enzyme inhibitors promises the start of a revolution in the treatment of several chronic diseases. Their efficacy and safety profile have been demonstrated in multiple trials and they have been licensed for the treatment of a number of diseases including RA and PsA. Moreover, the use of highly selective Janus Kinase Enzyme inhibitors is currently being studied aiming to reduce side effects compared with traditional JAKinibs, an example of that would be the recent FDA approved upadacitinib. The Janus Kinase Enzyme inhibitorsmay supplant the classical biologic agents in the treatment of autoimmune diseases, since they exhibitthe advantages of oral administration, simultaneous blockade of multiple cytokines, reversibility and the lack of immunogenicity.
Downloads
References
2. Furumoto Y, Gadina M. The arrival of JAK inhibitors: advancing the treatment of immune and hematologic disorders. BioDrugs 2013;27:431–8.
3. Peleg Rider, Yaron Carmi, Idan Cohen. Biologics for targeting inflammatory cytokines, clinical uses, and limitations. Int J Cell Biol 2016:11. https://doi.org/10.1155/2016/9259646.
4. Kotyla PJ. Are Janus kinase inhibitors superior over classic biologic agents in RA patients? Biomed Res Int 2018. Doi:10.1155/2018/7492904
5. Fleischmann R, Pangan AL, Mysler E, Bessette L, Peterfy C, Durez P, et al. A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. Arthritis Rheumatol 2018;70 (Suppl 10). https://acrabstracts.org/abstract/a-phase-3-randomized-double-blind-study-comparingupadacitinib-to-placebo-and-to-adalimumab-in-patients-with-active-rheumatoid-arthritis-withinadequate-response-to-methotrexate/. [Last accessed on 24 Aug 2019]
6. FDA Approves Upadacitinib (Rinvoq), New JAK Inhibitor for RA-Medscape; 2019.
7. Upadacitinib. AbbVie. Available from: https://www.abbvie.com/our-science/pipeline/upadacitinib.html. [Last accessed 24 Aug 2019]
8. Choy EH. Clinical significance of Janus Kinase inhibitor selectivity [published correction appears in rheumatology (Oxford). Rheumatology (Oxford). 2019;58:953–62.
9. Salvatore Bellinvia, Christopher J Edwards. JAK Inhibitors in the treatment algorithm of rheumatoid arthritis: a review. E Med J Rheumatol 2018;5:59-65.
10. Schwartz, Daniella M. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discovery 2017;17:78.
11. O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med 2015;66:311–28.
12. Yoshiya Tanaka. Recent progress and perspective in JAK inhibitors for rheumatoid arthritis: from bench to bedside. J Biochem 2015;158:173–9.
13. Clinical Trials. gov. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29. Identifier (NCT01710358), a study in moderate to severe rheumatoid arthritis (RA-BEAM); 2017. p. 15. Available from: https://clinicaltrials.gov/ct2/show/NCT01710358?term=ra-beamandrank=1 [Last accessed on 02 May 2019]
14. Taylor PC. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. New England J Med 2017;376:652-62.
15. ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). 2000. Identifier (NCT01877668), efficacy and safety of tofacitinib in psoriatic arthritis: comparator study (OPAL BROADEN); 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT01877668 [Last accessed on 02 May 2019]
16. Mease P. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. New England J Med 2017;377:1537-50.
17. Fleischmann R, Pangan AL, Song IH. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase 3, double?blind, randomized controlled trial. Arthritis Rhematol 2019;71:1788-800.
18. Mocsai A. What is the future of targeted therapy in rheumatology: biologics or small molecules? BMC Med 2014;12:43.
19. Wolf Henning Boehncke, Nicolo Costantino Brembilla. Immunogenicity of biologic therapies: causes and consequences. Expert Rev Clin Immunol 2018;14:6, 513-23.
20. Puig L, Gulliver W. Adverse reactions to biologics. Curr Probl Dermatol Basel Karger 2018;53:37-48.
21. George E Fragoulis, Iain B McInnes, Stefan Siebert, JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis. Rheumatology 2019;58:i43–i54.
22. Olumiant (baricitinib) tablets. Summary of Product Characteristics. Eli Lilly and Company Ltd; 2017. Available from: https://www.ema.europa.eu/en/documents/product-information/olumiant-epar-product-information_en.pdf [Last accessed on 02 Jul 2019].
23. Xeljanz/XeljanzXR (tofacitinib) [prescribing information]. New York, NY: Pfizer; 2018. Available from: https://www. accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf [Last accessed on 02 Jul 2019].
24. Xeljanz (tofacitinib) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada ULC; 2019. Available from: https://www.pfizer.ca/sites/default/files/201902/XELJANZ_PM_E_222743_04Feb2019.pdf [Last accessed on 02 Jul 2019].
25. Important safety information for Olumiant (baricitinib) tablets. Eli Lilly and Company Ltd 2018.
26. Peter C Taylor. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatology 2019;58:i17–i26.
27. Paik J, Deeks ED. Tofacitinib: a review in psoriatic arthritis. Drugs 2019;79:655.
28. Cutolo M. The kinase inhibitor tofacitinib in patients with rheumatoid arthritis: latest findings and clinical potential. Ther Adv Musculoskelet Dis 2013;5:3–11.