Clinical significance of Janus kinase inhibitors in the therapy of rheumatoid arthritis: achievements and prospects
https://doi.org/10.14412/1996-7012-2019-4-116-123
Abstract
Significant successes in the use of biological agents (BA) have been achieved in the treatment of rheumatoid arthritis (RA); nonetheless, about 36% of patients cannot respond to therapy or achieve the expected effect. A new area in the treatment of RA is the use of Janus kinase (JAK) inhibitors, targeted synthetic disease-modifying anti-rheumatic drugs (chemical molecules with a molecular weight <1 kDa for oral administration) that inhibit the activity of intracellular signaling systems. The authors consider the clinical achievements and prospects, which open the use of JAK inhibitors in the treatment of RA.
About the Authors
V. I. Mazurov
I.I.Mechnikov North-Western State Medical University
Russian Federation
Russian Federation
Vadim Ivanovich Mazurov
41, Kirochnaya Saint Petersburg 191015
I. B. Belyaeva
I.I.Mechnikov North-Western State Medical University
Russian Federation
Russian Federation
41, Kirochnaya Saint Petersburg 191015
References
1. Mazurov VI, Lila AM, Zotkin EG, editors. Klinicheskaya revmatologiya [Clinical rheumatology]. Moscow: FOLIANT; 2005. 515 p.
2. Mazurov VI, Trofimov EA. Revmatologiya. Farmakoterapiya bez oshibok: Rukovodstvo dlya vrachei [Rheumatology. Pharmacotherapy without mistakes: A guide for doctors]. Moscow: E-noto; 2017. 528 p.
3. Belyaeva IB, Mazurov VI, Trofimova TN, Trofimov EA. Rannii revmatoidnyi artrit: sovremennye vozmozhnosti diagnostiki i lecheniya [Early rheumatoid arthritis: modern possibilities of diagnosis and treatment]. Saint-Petersburg: Medforum; 2017. 138 p.
4. Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical guidelines. Rheumatology]. Moscow: GEOTAR-Media; 2017. 464 p.
5. Nasonov EL. Genno-inzhenernye biologicheskie preparaty v lechenii revmatoidnogo artrita [Genetically engineered biological drugs in the treatment of rheumatoid arthritis]. Moscow: IMA-PRESS; 2013. 552 p.
6. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016 Jan;68(1):1-25. doi: 10.1002/acr.22783. Epub 2015 Nov 6.
7. Charles-Schoeman C, Burmester G, Nash P, et al. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological diseasemodifying anti-rheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 0.1136/annrheumdis-2014-207178. Epub 2015 Aug 1
8. Giacomelli R, Afeltra A, Alunno A, et al. Guidelines for biomarkersin autoimmune rheumatic diseases – evidence basedanalysis. Autoimmun Rev. 2019 Jan;18(1):93-106. doi: 10.1016/j.autrev.2018.08.003. Epub 2018 Nov 5.
9. Choy EH. Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology (Oxford). 2019 Jun 1;58(6):953-962. doi: 10.1093/rheumatology/key339.
10. Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as atherapeutic strategy for immune and inflammatory diseases. doi: 10.1038/nrd.2017.201
11. Banerjee S, Biehl A, Gadina M, et al. JAK-STAT Signaling as aTarget for Inflammatory and Autoimmune Diseases: Current andFuture Prospects. Drugs. 2017 Apr;77(5):521-546. doi: 10.1007/s40265-017-0701-9.
12. Gadina M, Johnson C, Schwartz D, et al. Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs. J Leukoc Biol. 2018 Sep;104(3): 499-514. doi: 10.1002/JLB.5RI0218-084R. Epub 2018 Jul 12.
13. Nasonov EL, Lila AM. Janus kinase inhibitors in immuno-inflammatory rheumatic diseases: new opportunities and prospects. Nauchno-prekticheskaya revmatologiya = Rheumatology Science and Practice. 2019;57(1): 8-16. (In Russ.). doi: 10.14412/1995-4484-2019-8-16
14. Nasonov EL. New approaches to pharmacotherapy of rheumatoid arthritis: tofacitinib. Nauchnoprekticheskaya revmatologiya = Rheumatology Science and Practice. 2014;52(2):209-21. (In Russ.). doi: 10.14412/1995-4484-2014-209-221
15. Charles-Schoeman C, Burmester G, Nash P, et al. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological diseasemodifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14.
16. Kunwar S, Collins CE, Constantinescu F. Baricitinib, a Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematicliterature review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2018 Oct;37(10):2611-2620. doi: 10.1007/s10067-018-4199-7. Epub 2018 Jul 13.
17. Shi JG, Chen X, Lee F, et al. The pharmacokinetics, pharmacodynamics,and safety of baricitinib, an oral JAK 1/2 inhibitor, inhealthy volunteers. J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.
18. Dhillon S. Tofacitinib: A Review in Rheumatoid Arthritis. Drugs. 2017 Dec;77(18): 1987-2001. doi: 10.1007/s40265-017-0835-9.
19. Charles-Schoeman C, Burmester G, Nash P, et al. Efficacy andsafety of tofacitinib following inadequate response to conventionalsynthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14.
20. Winthrop KL. The emerging safety profile of JAK inhibitors inrheumatic disease. Nat Rev Rheumatol. 2017 Apr;13(4):234-243. doi: 10.1038/nrrheum.2017.23. Epub 2017 Mar 2.
21. Strand V, Kavanaugh A, Kivitz AJ, et al. Long-Term Radiographic and PatientReported Outcomes in Patients with Rheumatoid Arthritis Treated with Tofacitinib: ORAL Start and ORAL Scan Post-hoc Analyses. Rheumatol Ther. 2018 Dec;5(2):341-353. doi: 10.1007/s40744-018-0113-7. Epub 2018 May 14.
22. Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662. doi: 10.1056/NEJMoa1608345.
23. Fleischmann R, Mysler E, Hall S, et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate,and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet. 2017 Jul 29;390(10093):457-468. doi: 10.1016/S0140-6736(17)31618-5. Epub 2017 Jun 16.
24. Genovese MC, Kremer J, Zamani O, et al. Baricitinib inpatients with refractory rheumatoid arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247.
25. Taylor PC. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatology (Oxford). 2019 Feb 1; 58(Supplement_1):i17-i26. doi: 10.1093/rheumatology/key225.
26. Roman Muller. Jak ingibitors in 2019, synthetic review in 10 poins. Eur J Intern Med. 2019 Aug;66:9-17. doi: 10.1016/j.ejim.2019.05.022. Epub 2019 Jun 6.
27. Genovese MC, Smolen JS, Weinblatt ME, et al. Efficacyand safety of ABT-494, a selective JAK-1 inhibitor, in aphase IIb study in patients with rheumatoid arthritis and aninadequate response to methotrexate. Arthritis Rheumatol. 2016 Dec;68(12):2857-2866. doi: 10.1002/art.39808.
28. Westhovens R, Taylor PC, Alten R, et al. Filgotinib(GLPG0634/GS-6034), an oral JAK1 selective inhibitor, iseffective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-findingstudy (DARWIN 1). Ann Rheum Dis. 2017 Jun;76(6):998-1008. doi: 10.1136/annrheumdis-2016-210104. Epub 2016 Dec 19.
29. Genovese MC, Greenwald M, Codding C, et al. Peficitinib,a JAK inhibitor, in combination with limited conventionalsynthetic disease-modifying antirheumatic drugs in thetreatment of moderate-to-severe rheumatoid arthritis. Arthritis Rheumatol. 2017 May;69(5):932-942. doi: 10.1002/art.40054.
30. Fleischmann RM, Damjanov NS, Kivitz AJ, et al. A randomized, double-blind, placebo-controlled, twelve-week,dose-ranging study of decernotinib, an oral selective JAK-3 inhibitor, as monotherapy in patients with activerheumatoid arthritis. Arthritis Rheumatol. 2015 Feb;67(2):334-43. doi: 10.1002/art.38949.
31. Burmester GR, Kremer JM, Van den Bosch F, et al. Safetyand efficacy of upadacitinib in patients with rheumatoidarthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139): 2503-2512. doi: 10.1016/S0140-6736(18)31115-2. Epub 2018 Jun 18.
32. Genovese MC, Fleischmann R, Combe B, et al. Safety andefficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (SELECT-BEYOND): a double-blind,randomised controlled phase 3 trial. Lancet. 2018 Jun 23;391(10139):25132524. doi: 10.1016/S0140-6736(18)31116-4. Epub 2018 Jun 18.
33. Nasonov EL, Lila AM. Inhibition of interleukin 6 in immune inflammatory rheumatic diseases: achievements, prospects, and hopes. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2017; 55(6):590-9. (In Russ.). doi: 10.14412/1995-4484-2017-590-599
34. Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety oftofacitinib for the treatment of rheumatoid arthritis up to8.5 years: integrated analysis of data from the globalclinical trials. Ann Rheum Dis. 2017 Jul; 76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
35. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profileof baricitinib for the treatment of rheumatoid arthritis up to 5.5 years: an updated integrated safety analysis. ACR/ARHP Annual Meeting. San Diego: 38 November 2017. Abstr. 511.
36. Winthrop KL, Curtis JR, Lindsey S, et al. Herpes zoster andtofacitinib. Clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol. 2017 Oct;69(10):1960-1968. doi: 10.1002/art.40189. Epub 2017 Sep 6.
37. Winthrop KL, Wouters AG, Choy EH, et al. The safety andimmunogenicity of live zoster vaccination in patients withrheumatoid arthritis before starting tofacitinib: a randomized phase II trial. Arthritis Rheumatol. 2017 Oct;69(10):1969-1977. doi: 10.1002/art.40187. Epub 2017 Sep 6.
38. Weinblatt M, Taylor PC, Burmester G, et al. Cardiovascularsafety during treatment with baricitinib in patients withrheumatoid arthritis. ACR/ARHP Annual Meeting. San Diego: 38 November 2017. Abstr. 499
39. Xie F, Yun H, Bernatsky S, Curtis JR. Brief report: risk of gastrointestinal perforation among rheumatoid arthritis patients receiving tofacitinib, tocilizumab, or other biologic treatments. Arthritis Rheumatol. 2016 Nov;68(11):2612-2617. doi: 10.1002/art.39761.
40. Smolen JS, Genovese MC, Takeuchi T. Safety profile ofbaricitinib in patients with active rheumatoid arthritis: anintegrated analysis. European League Against Rheumatism (EULAR). London; 8–11 June 2016. Poster THU0166.
41. Schulze-Koops H, Strand V, Nduaka C, et al. Analysis ofhaematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-termextension studies. Rheumatology (Oxford). 2017 Jan;56(1):46-57. doi: 10.1093/rheumatology/kew329. Epub 2016 Oct 22.
42. Kremer JM, Checn L, Saifan CG, et al. Analysis of neutrophils, lymphocytes, and platelets in pooled phase 2 andphase 3 studies of baricitinib for rheumatoid arthritis. European League Against Rheumatism (EULAR). Madrid; 14–17 June 2017. Poster 1325.
43. Charles-Schoeman C, Gonzalez-Gay MA, Kaplan I, et al. Effects of tofacitinib and other DMARDs on lipid profiles in rheumatoid arthritis: implications for the rheumatologist. Semin Arthritis Rheum. 2016 Aug;46(1): 71-80. doi: 10.1016/j.semarthrit.2016.03.004. Epub 2016 Mar 9.
44. Isaacs JD, Zuckerman A, Krishnaswami S, et al. Changesin serum creatinine in patients with active rheumatoid arthritis treated with tofacitinib: results from clinical trials. Arthritis Res Ther. 2014 Jul 25;16(4):R158. doi: 10.1186/ar4673.
45. McInnes IB, Kremer J, Emery P, et al. Lipid profile andeffect of statin treatment in pooled phase 2 and phase 3baricitinib studies. 2016 ACR/ARHP Annual Meeting. Abstract No. 3023.
Review
For citations:
Mazurov VI, Belyaeva IB. Clinical significance of Janus kinase inhibitors in the therapy of rheumatoid arthritis: achievements and prospects. Sovremennaya Revmatologiya=Modern Rheumatology Journal. 2019;13(4):116-123. (In Russ.) https://doi.org/10.14412/1996-7012-2019-4-116-123
Views:
1309
Email this article 