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Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I)

https://doi.org/10.14412/1995-4484-2020-62-79

Abstract

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IIRDs) and designing a wide range of biological agents (BAs) are the major achievements of 21st century medicine. A new promising area of pharmacotherapy for IIRDs is associated with the design of so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors, called jakinibs. The first representative of the class of JAK inhibitors is tofacitinib (TOFA), which has been registered for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis. The review (Part I) presents new data on the efficacy and safety of TOFA in RA and discusses the role of TOFA in the treatment of RA as part of the treat-to-target strategy and new EULAR recommendations. Part II of the review will provide data on the use of TOFA in other IIRDs.

About the Authors

E. L. Nasonov
V.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

34A, Kashirskoe Shosse, Moscow 115522; 8, Trubetskaya St., Build. 2, Moscow 119991


Competing Interests: not


A. S. Avdeeva
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

34A, Kashirskoe Shosse, Moscow 115522


Competing Interests: not


A. M. Lila
V.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

34A, Kashirskoe Shosse, Moscow 115522; 2/1, Barrikadnaya St., Build. 1, Moscow 125993


Competing Interests: not


References

1. Kubo S, Yamaoka K, Amano K, et al. Discontinuation of tofaci-tinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study. Rheumatology (Oxford). 2017;56(8):1293-301. doi: 10.1093/rheumatology/kex068

2. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis. 2018;77(2):175-87. doi: 10.1136/annrheumdis-2017-211555

3. Nasonov EL. Pharmacotherapy for rheumatoid arthritis: New strategy, new targets. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(4):409-19 (In Russ.). doi: 10.14412/1995-4484-2017-409-419

4. Perez-Roman DI, Ortiz-Haro AB, Ruiz-Medrano E, et al. Outcomes after rheumatoid arthritis patients complete their participation in a long-term observational study with tofacitinib combined with methotrexate: practical and ethical implications in vulnerable populations after tofacitinib discontinuation. RheumatolInt. 2018;38(4):599-606. doi: 10.1007/s00296-017-3910-3

5. Mori S, Ueki Y. Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study. Clin Rheumatol. 2019 Aug 9. doi: 10.1007/s10067-019-04721-z

6. Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev DrugDiscov. 2017;16(12):843-62. doi: 10.1038/nrd.2017.201

7. Nasonov EL, Lila AM. Janus kinase inhibitors in immuno-inflammatory rheumatic diseases: new opportunities and prospects. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2019;57(1):8-16 (In Russ.). doi: 10.14412/1995-4484-2019-8-16

8. Kaine J, Tesser J, DeMasi R, et al. Efficacy of tofacitinib after temporary discontinuation in patients with rheumatoid arthritis: analysis of Data from open-label long-term extension studies. Ann Rheum Dis. 2018. doi: 10.1136/annrheumdis-2018-eular.3755

9. Takeuchi T, Genovese MC, Haraoui B, et al. Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study. Ann Rheum Dis. 2019;78(2):171-8. doi: 10.1136/annrheumdis-2018-213271

10. Nasonov EL. New approaches to pharmacotherapy of rheumatoid arthritis: tofacitinib. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2014;52(2):209-21 (In Russ.). doi: 10.14412/1995-4484-2014-209-221

11. Atzeni F, Masala IF, di Franco M, Sarzi-Puttini P. Infections in rheumatoid arthritis. Curr Opin Rheumatol. 2017;29(4):323-30. doi: 10.1097/BOR.0000000000000389

12. Dhillon S. Tofacitinib: A Review in Rheumatoid Arthritis. Drugs. 2017 Dec;77(18):1987-2001. doi: 10.1007/s40265-017-0835-9

13. Berekmeri A, Mahmood F, Wittmann M, Helliwell P. Tofacitinib for the treatment of psoriasis and psoriatic arthritis. Expert Rev Clin Immunol. 2018;14(9):719-30. doi: 10.1080/1744666X.2018

14. Kivitz AJ, Cohen S, Keystone E, et al. A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population. Semin Arthritis Rheum. 2018;48(3):406-15. doi: 10.1016/j.semarthrit.2018.07.006

15. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017;13(5):320. doi: 10.1038/nrrheum.2017.51

16. Ly K, Beck KM, Smith MP, et al. Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives. Psoriasis (Auckl). 2019;9:97-107. doi: 10.2147/PTT.S161453

17. D'Amico F, Parigi TL, Fiorino G, et al. Tofacitinib in the treatment of ulcerative colitis: efficacy and safety from clinical trials to real-world experience. Ther Adv Gastroenterol. 2019 May 16;12:1756284819848631. doi: 10.1177/1756284819848631

18. Harigai M. Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford). 2019;58 Suppl 1:i34-i42. doi: 10.1093/rheumatology/key287

19. Nasonov EL, Abdulganieva DI, Fairushina IF. Place of tofacitinib in the treatment of inflammatory bowel disease. Terapevticheskii Arkhiv. 2019;91(2):101-8 (In Russ.). doi: 10.26442/004036602019;2

20. Charles-Schoeman C, DeMasi R, Valdez H, et al. Risk Factors for Major Adverse Cardiovascular Events in Phase III and LongTerm Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis. Arthritis Rheum. 2019;71(9):1450-9. doi: 10.1002/art.40911

21. Howell MD, Kuo FI, Smith PA. Targeting the Janus Kinase Family in Autoimmune Skin Diseases. Front Immunol. 2019 Oct 9;10:2342. doi: 10.3389/fimmu.2019.02342

22. Xie W, Huang Y, Xiao S, et al. Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials. Ann Rheum Dis. 2019;78(8):1048-54. doi: 10.1136/annrheumdis-2018-214846

23. Jamilloux Y, El Jammal T, Vuitton L, et al. JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2019 Sep 11:102390. doi: 10.1016/j.autrev.2019.10

24. Nurmohamed M, Choy E, Lula S, et al. The Impact of Biologics and Tofacitinib on Cardiovascular Risk Factors and Outcomes in Patients with Rheumatic Disease: A Systematic Literature Review. Drug Saf. 2018;41(5):473-88. doi: 10.1007/s40264-017-0628-9

25. Virtanen A, Haikarainen T, Raivola J, Silvennoinen O. Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases. BioDrugs. 2019;33(1):15-32. doi: 10.1007/s40259-019-00333

26. Charles-Schoeman C, Fleischmann R, Davignon J, et al. Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib. Arthritis Rheum. 2015;67(3):616-25. doi: 10.1002/art.38974

27. El Jammal T, Gerfaud-Valentin M, Seve P, Jamilloux Y. Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum. Joint Bone Spine. 2019 Sep 12. doi: 10.1016/j.jbspin.2019.09.005

28. McInnes IB, Kim HY, Lee SH, et al. Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann Rheum Dis. 2014;73(1):124-31. doi: 10.1136/annrheumdis-2012-2024

29. Smolen JS, van der Heijde D, Machold KP, et al. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann Rheum Dis. 2014;73(1):3-5. doi: 10.1136/annrheumdis-2013-204317

30. Kume K, Amano K, Yamada S, et al. Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study. Rheumatol Int. 2017;37(12):2079-85. doi: 10.1007/s00296-017-3844-9

31. Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-77. doi: 10.1136/annrheumdis-2016-210715

32. Luisse A, Pierini F, Gandino I, et al. Effect of tofacitinib on the qualityve profile of high density lipoproteins molecules in patients with rheumatoid arthritis. Arthritis Rheum. 2019;71 Suppl 10:abstract 1415.

33. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheum. 2016;68(1):1-26. doi: 10.1002/art.39480

34. Schulze-Koops H, Strand V, Nduaka C, et al. Analysis of haemato-logical changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies. Rheumatology (Oxford). 2017;56(1):46-57. doi: 10.1093/rheumatology/kew329

35. Daien C, Hua C, Gaujoux-Viala C, et al. Update of French society for rheumatology recommendations for managing rheumatoid arthritis. Joint Bone Spine. 2019 Mar;86(2):135-50. doi: 10.1016/j.jbspin.2018.10.002

36. Mariette X, Chen C, Biswas P, et al. Lymphoma in the tofacitinib rheumatoid arthritis clinical development program. Arthritis Care Res (Hoboken). 2017. doi: 10.1002/acr.23421

37. Lau CS, Chia F, Harrison A, et al. Asia Pacific League of Associations for Rheumatology APLAR rheumatoid arthritis treatment recommendations. Int J Rheum Dis. 2015;18:685-713. doi: 10.1111/1756-185X.12754

38. Curtis JR, Lanas A, John A, et al. Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(12):1819-28. doi: 10.1002/acr.21764

39. Cardiel MH, Diaz-Borjon A, Vazquez del Mercado Espinosa M, et al. Mexican College of Rheumatology Update of the Mexican College of Rheumatology guidelines for the pharmacologic treatment of rheumatoid arthritis. Reumatol Clin. 2014;10:227-40. doi: 10.1016/j.reuma.2013.10.006

40. Mota LMHD, Kakehasi AM, Gomides APM, et al. 2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis. Adv Rheumatol. 2018 May 24;58(1):2. doi: 10.1186/s42358-018-0005-0

41. Charles-Schoeman C, Burmester G, Nash P, et al. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178

42. Ataman S, Sunar I, Yilmaz G, et al. Turkish League Against Rheumatism (TLAR) Recommendations for the Pharmacological Management of Rheumatoid Arthritis: 2018 Update Under Guidance of Current Recommendations. Arch Rheumatol. 2018 Jul 9;33(3):251-71. doi: 10.5606/ArchRheumatol.2018.6911

43. Winthrop KL, Curtis JR, Lindsey S, et al. Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy. Arthritis Rheum. 2017;69(10):1960-8. doi: 10.1002/art.40189

44. Ho CTK, Mok CC, Cheung TT, et al. Hong Kong Society of Rheumatology. Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology. Clin Rheumatol. 2019 Sep 4. doi: 10.1007/s10067-019-04761-5

45. Curtis JR, Xie F, Bernatsky S, et al. Herpes zoster in tofacitinib users with and without concomitant methotrexate and glucocorticoids. Arthritis Rheum. 2019;70 Suppl 10:abstract 665.

46. Alhajeri H, Abutiban F, Al-Adsani W, et al. Kuwait association of rheumatology 2018 treatment recommendations for patients with rheumatoid arthritis. Rheumatol Int. 2019 Sep;39(9):1483-97. doi: 10.1007/s00296-019-04372-y

47. Desai RJ, Pawar A, Weinblatt ME, Kim SC. Comparative Risk of Venous Thromboembolism in Rheumatoid Arthritis Patients Receiving Tofacitinib Versus Those Receiving Tumor Necrosis Factor Inhibitors: An Observational Cohort Study. Arthritis Rheum. 2019;71(6):892-900. doi: 10.1002/art.40798

48. Cardiel MH, Carrillo S, Perez M, et al. Update of the Mexican College of Rheumatology Guidelines for the Pharmacological Treatment of Rheumatoid Arthritis, 2018. Reumatol Clin. 2019 May 15. doi: 10.1016/j.reuma.2019.04.002

49. Weinblatt MTP, Burmester GR, Witt S, et al. Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis [abstract]. Arthritis Rheum. (Hoboken, NJ). 2017;69 Suppl 10.

50. Nasonov EL, editor. Revmatologiya. Rossiiskie klinicheskie rekomendatsii [Rheumatology. Russian clinical guidelines]. Moscow: GEOTAR-Media; 2017. 456 p. (In Russ.).

51. Kim SC, Schneeweiss S, Liu J, Solomon DH. Risk of venous thromboembolism in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65:1600-7. doi: 10.1002/acr.22039

52. Singh JA, Guyatt G, Ogdie A, et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Care Res (Hoboken). 2019;71(1):2-29. doi: 10.1002/acr.23789

53. Clowse MEB, Feldman SR, Isaacs JD, et al. Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf. 2016;39(8):755-62. doi: 10.1007/s40264-016-0431-z

54. Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374-84. doi: 10.1038/ni.3691

55. He Y, Wong AYS, Chan EW, et al. Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systemic review and meta-analysis. BMCMusculoskelet Disord. 2013;14:298. doi: 10.1186/1471-2474-14-298

56. McInnes IB, Byers NL, Higgs RE, et al. Comparison of barici-tinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations. Arthritis Res Ther. 2019;21(1):183. doi: 10.1186/s13075-019-1964-1

57. Berhan A. Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies. BMC Musculoskelet Disord. 2013;14:332. doi: 10.1186/147-2474-14-332

58. Choy EH. Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology (Oxford). 2019;58(6):953-62. doi: 10.1093/rheumatology/key339. Erratum in: Rheumatology (Oxford). 2019 Jun 1;58(6):1122.

59. Kawalec P, Mikrut A, Wisniewska N, Pilc A. The effectiveness of tofacitinib, a novel Janus kinase inhibitor. In the treatment of rheumatoid arthritis: a systemic review and metha-analysis. Clin Rheumatol. 2013;32:1414-24. doi. 10.1007/s10067-013-2329-9

60. Dowty ME, Lin TH, Jesson MI, et al. Janus kinase inhibitors for the treatment of rheumatoid arthritis demonstrate similar profiles of in vitro cytokine receptor inhibition. Pharmacol Res Perspect. 2019;7(6):e00537. doi: 10.1002/prp2.537

61. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2016 May 13;(5):CD012183. doi: 10.1002/14651858.CD012183

62. Cohen S, Zwillich SH, Chow L, et al. Co-administration of JAK inhibitor CP-690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis without need for dose adjustment. Br J Clin Pharmacol. 2010;69:143-51. doi: 10.1m/j.1365-2125.2009.03570.x

63. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA). Cochrane Database Syst Rev. 2016 Nov 17;11:CD012437. doi: 10.1002/14651858.CD012437

64. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. doi: 10.1038/nrdp.2018

65. Singh JA, Hossain A, Mudano AS, et al. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2017;5:CD012657. doi: 10.1002/14651858.CD012657

66. Ghoreshi K, Jesson M, Li X, et al. Modulation of innate and adaptive immunity responses by tofacitinib. J Immunol. 2011;186:4234-43. doi: 10.4049/jimmunol.1003668

67. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network metaanalysis. Cochrane Database Syst Rev. 2017;3:CD012591. doi: 10.1002/14651858.CD012591

68. Hodge JA, Kawabata TT, Krishnaswami S, et al. The mechanism of action of tofacitinib — an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34(2):318-28.

69. Bergrath E, Gerber RA, Gruben D, et al. Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network MetaAnalysis. Int JRheumatol. 2017;2017:8417249. doi: 10.1155/2017/8417249

70. Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12(1):25-36. doi: 10.1038/nrrheum.2015.167

71. Camean-Castillo M, Gimeno-Ballester V, Rios-Sanchez E, et al. Network meta-analysis of tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients. J Clin Pharm Then. 2019;44(3):384-96. doi: 10.1111/jcpt.12795

72. Fleischmann R, Cutolo M, Genovese MC, et al. Phase Ilb doseranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012;64(3):617-29. doi: 10.1002/art.33383

73. Venerito V, Lopalco G, Cacciapaglia F, et al. A Bayesian mixed treatment comparison of efficacy of biologics and small molecules in early rheumatoid arthritis. Clin Rheumatol. 2019;38(5):1309-17. doi: 10.1007/s10067-018-04406-z

74. Kremer JM, Bloom BJ, Breedveld FC, et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009;60(7):1895-905. doi: 10.1002/art.24567

75. Huang F, Luo Z-C. Adverse drug events associated with 5 mg versus 10 mg tofacitinib (Janus kinase inhibitor) twice daily for the treatment of autoimmune diseases: a systemic review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2019;38:523-34. doi: 10.1007/s10067-018-4299-5

76. Kremer JM, Cohen S, Wilkinson BE, et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background MTX in patients with active rheumatoid arthritis and an inadequate response to MTX alone. Arthritis Rheum. 2012;64(4):970-81. doi: 10.1002/art.33419

77. Song GG, Choi SJ, Lee YH. Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. Int J Rheum Dis. 2019;22(8):1563-71. doi: 10.1111/1756-185X.136

78. Tanaka Y, Suzuki M, Nakamura H, et al. Tofacitinib Study Investigators. Phase II study of tofacitinib (CP-690,550) combined with MTX in patients with rheumatoid arthritis and an inadequate response to MTX. Arthritis Care Res (Hoboken). 2011;63:1150-8. doi: 10.1002/acr.20494

79. Jegatheeswaran J, Turk M, Pope JE. Comparison of Janus kinase inhibitors in the treatment of rheumatoid arthritis: a systemic literature review. Immunotherapy. 2019;11(8):737-54. doi: 10.2217/imt-2018-0178

80. Tanaka Y, Takeuchi T, Yamanaka H, et al. Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, Phase 2 study. Mod Rheumatol. 2015;25:514-21. doi: 10.3109/14397595.2014.995875

81. Edwards C, Sawant R, Du E, et al. A matching-adjusted indirect comparison (MAIC) of upadacitinib versus tofacitinib in csDMARD-IR with moderate to severe rheumatoid arthritis. (RA). Ann Rheum Dis. 2019. doi: 10.1136/annrheumdis-2019-eular.7189

82. Van der Heijde D, Tanaka Y, Fleischmann R, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving MTX twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013;65(3):559-70. doi: 10.1002/art.37816

83. Dougados M, van der Heijde D, Chen Y, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017;76(1):88-95. doi: 10.1136/annrheumdis-2016-210094

84. Van der Heijde D, Strand V, Tanaka Y, et al. ORAL Scan Investigators. Tofacitinib in Combination "With Methotrexate in Patients With Rheumatoid Arthritis: Clinical Efficacy, Radiographic, and Safety Outcomes From a Twenty-Four-Month, Phase III Study. Arthritis Rheum. 2019;71(6):878-91. doi: 10.1002/art.40803

85. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243-52. doi: 10.1056/NEJMoa1507247

86. Van Vollenhoven R, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367:508-19. doi: 10.1056/NEJMoa1112072

87. Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheum. 2017;69(3):506-17.

88. Burmester GR, Blanco R, Charles-Schoeman CH, Wollenhaupt J. Tofacitinib (CP-690,550) in combination with MTX in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase III trial. Lancet. 2013;381:451-60. doi: 10.1016/S0140-6736(12)61424-X

89. Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652-62. doi: 10.1056/NEJMoa1608345

90. Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495-507. doi: 10.1056/NEJMoa1109071

91. Genovese MC, Smolen JS, Weinblatt ME, et al. Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a Phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheum. 2016;68(12):2857-66. doi: 10.1002/art.39808

92. Fleischmann R, Mysler E, Hall S, et al; ORAL Strategy Investigators. Efficacy and safety of tofacitinib monotherapy, tofacitinib with MTX, and adalimumab with MTX in patients with rheumatoid arthritis (ORAL Strategy): a phase IIIb/IV, double-blind, head-to-head, randomised controlled trial. Lancet. 2017;390(10093):457-68. doi: 10.1016/S0140-6736(17)31618-5

93. Burmester GR, Kremer JM, van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomized, double-blind, placebo-controlled Phase III trial. Lancet. 2018;391(10139):2503-12. doi: 10.1016/S0140-6736(18)31115-2

94. Kremer J, Li ZG, Hall S, et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013;159(4):253-61. doi: 10.7326/0003-4819-159-4-201308200-00006

95. Kremer JM, Emery P, Camp HS, et al. A Phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to antitumor necrosis factor therapy. Arthritis Rheum. 2016;68(12):2867-77. doi: 10.1002/art.39801

96. Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus MTX in rheumatoid arthritis. N Engl J Med. 2014;370:2377-86. doi: 10.1056/NEJMoa1310476

97. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomized controlled Phase III trial. Lancet. 2018;391(10139):2513-24. doi: 10.1016/S0140-6736(18)31116-4

98. Genovese MC, van Vollenhoven RF, Wilkinson B, et al. Switching from adalimumab to tofacitinib in the treatment of patients with rheumatoid arthritis. Arthritis Res Ther. 2016;18:145. doi: 10.1186/s13075-016-1049-3

99. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. A Phase 3, Randomized, Controlled Trial Comparing Upadacitinib Monotherapy to MTX Monotherapy in MTX-Naive Patients with Active Rheumatoid Arthritis [abstract]. Arthritis Rheum. 2018;70 Suppl 10. doi: 10.1093/rheumatology/kez106.058

100. Gossec L, Dougados M, Dixon W. Patient-reported outcomes as endpoints in clinical trials in rheumatoid arthritis. RMD Open. 2015;1(1):e000019. doi: 10.1136/rmdopen-2014-000019

101. Fleischmann R, Pangan AL, Song IH, et al. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheum. 2019 Nov;71(11):1788-800. doi: 10.1002/art.41032

102. Fautrel B, Alten R, Kirkham B, et al. Call for action: how to improve use of patient-reported outcomes to guide clinical decision making in rheumatoid arthritis. Rheumatol Int. 2018;38(6):935-47. doi: 10.1007/s00296-018-4005-5

103. Tofacitinib: Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004214/WC500224911.pdf

104. Strand V, Khanna D. The impact of rheumatoid arthritis and treatment on patients' lives. Clin Exp Rheumatol. 2010;28:S32-40.

105. Smolen JS, Aletaha D, Gruben D, et al. Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria. Arthritis Rheum. 2017;69(4):728-34. doi: 10.1002/art.39996

106. Rendas-Baum R, Bayliss M, Kosinski M, et al. Measuring the effect of therapy in rheumatoid arthritis clinical trials from the patient's perspective. Curr Med Res Opin. 2014;30:1391-403. doi: 10.1185/03007995.2014.896328

107. Meissner Y, Baganz L, Schneider M, et al. Baricitinib and Tofacitinib in Real Life - Does Obesity Impact Response to Janus Kinase Inhibitor Therapy in Rheumatoid Arthritis? [abstract]. Arthritis Rheum. 2018;70 Suppl 10.

108. Matcham F, Scott IC, Rayner L, et al. The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014;44:123-30. doi: 10.1016/j.semarthrit.2014.05.001

109. Singh S, Facciorusso A, Singh AG, et al. Obesity and response to anti-tumor necrosis factorа agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis. PLoSOne. 2018;13(5):e0195123. doi: 10.1371/journal.pone.0195123

110. Strand V, van Vollenhoven RF, Lee EB, et al. Tofacitinib or adali-mumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis. Rheumatology (Oxford). 2016;55:1031-41. doi: 10.1093/rheumatology/kev442

111. Rigby WFC, Lampl K, Low JM, Furst DE. Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs. Int J Rheumatol. 2017;2017:9614241. doi: 10.1155/2017/9614241

112. Strand V, Kremer JM, Gruben D, et al. Tofacitinib in combination with conventional disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: patient-reported outcomes from a phase III randomized controlled trial. Arthritis Care Res (Hoboken). 2017;69:592-8. doi: 10.1002/acr.23004

113. Calabrese LH, Abud-Mendoza C, Lindsey SM, et al. Live Zoster Vaccine in Patients with Rheumatoid Arthritis Treated with Tofacitinib with or without Methotrexate, or Adalimumab with Methotrexate. Arthritis Care Res (Hoboken). 2019 Jun 17. doi: 10.1002/acr.24010

114. Strand V, Burmester GR, Zerbini CA, et al. Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: patient-reported outcomes from a phase III trial. Arthritis Care Res (Hoboken). 2015;67:475-83. doi: 10.1002/acr.22453

115. Winthrop KL, Silverfield J, Racewicz A, et al. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016;75:687-95. doi: 10.1136/annrheumdis-2014-207191

116. Strand V, Lee EB, Fleischmann R, et al. Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial. RMD Open. 2016;2:e000308. doi: 10.1136/rmdopen-2016-000308

117. Goodman SM, Springer B, Guyatt G, et al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Rheum. 2017;69:1538-51. doi: 10.1002/art.40149

118. Strand V, Kremer J, Wallenstein G, et al. Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther. 2015;17:307. doi: 10.1186/s13075-015-0825-9

119. Gremese E, Alivernini S, Tolusso B, et al. JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy. J Leukoc Biol. 2019;106(5):1063-8. doi: 10.1002/JLB.5RU0519-145R

120. Strand V, Mysler E, Moots RJ, et al. Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial. RMD Open. 2019;5(2):e001040. doi: 10.1136/rmdopen-2019-001040

121. Kronzer VL, Crowson CS, Sparks JA, et al. Family history of rheumatologic, autoimmune, and non-autoimmune diseases and risk of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2019 Nov 30. doi: 10.1002/acr.24115

122. Strand V, Kavanaugh A, Kivitz AJ, et al. Long-Term Radiographic and Patient-Reported Outcomes in Patients with Rheumatoid Arthritis Treated with Tofacitinib: ORAL Start and ORAL Scan Post-hoc Analyses. Rheumatol Ther. 2018;5(2):341-53. doi: 10.1007/s40744-018-0113-7

123. Emamifar A, Jensen Hansen IM. The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency and other comorbid autoimmune diseases on treatment outcome in patients with rheumatoid arthritis: An exploratory cohort study. Medicine (Baltimore). 2018;97(21):e10865. doi: 10.1097/MD.0000000000010865

124. Choy EH. Effect of biologics and targeted synthetic disease-modifying anti-rheumatic drugs on fatigue in rheumatoid arthritis. Rheumatology (Oxford). 2019 Nov 1;58 Suppl 5:v51-v55. doi: 10.1093/rheumatology/kez389

125. Citera G, Jain R, Irazoque F, et al. Tofacitinib in Patients with Rheumatoid Arthritis and Indicative of Depression And/or Anxiety: A Post Hoc Analysis of Phase 3 and Phase 3b/4 Clinical Trials [abstract]. Arthritis Rheum. 2019; 71 Suppl 10. Available from: https://acrabstracts.org/abstract/tofacitinib-in-patients-with-rheumatoid-arthritis-and-indicative-of-depression-and-or-anxiety-a-post-hoc-analysis-of-phase-3-and-phase-3b-4-clinical-trials/

126. Wollenhaupt J, Silverfield J, Lee EB, et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open label, long term extension studies. J Rheumatol. 2014;41:837-52. doi: 10.3899/jrheum.130683

127. Yamanaka H, Tanaka Y, Takeuchi T, et al. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background MTX, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study. Arthritis Res Ther. 2016;18:34. doi: 10.1186/s13075-016-0932-2

128. Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017;76:1253-62. doi: 10.1136/annrheumdis-2016-210457

129. Wollenhaupt J, Lee EB, Curtis JR, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019;21(1):89. doi: 10.1186/s13075-019-1866-2

130. Pope JE, Keystone E, Jamal S, et al. Persistence of tofacitinib in the treatment of rheumatoid arthritis in open-label, long-term extension studies up to 9.5 years. ACR Open. 2019;1:73-82. doi: 10.1002/acr2/1010

131. Fleischmann R, Wollenhaupt J, Cohen S, et al. Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis. Rheumatol Ther. 2018;5(1):203-14. doi: 10.1007/s40744-018-0093-7

132. Charles-Schoeman C, van der Heijde D, Burmester GR, et al. Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies. J Rheumatol. 2018;45(2):177-87. doi: 10.3899/jrheum.170486

133. Fleischmann R, Mease PJ, Schwartzman S, et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group. Clin Rheumatol. 2017;36(1):15-24. doi: 10.1007/s10067-016-3436-1

134. Emery P, Pope JE, Kruger K, et al Efficacy of Monotherapy with Biologics and JAK Inhibitors for the Treatment of Rheumatoid Arthritis: A Systematic Review. Adv Ther. 2018;35(10):1535-63. doi: 10.1007/s12325-018-0757-2

135. Doria A, Zavaglia D. Monotherapy is a relevant option in rheumatoid arthritis treatment: a literature review. Clin Exp Rheumatol. 2019;37(5):862-71.

136. Luis M, Freitas J, Costa F, et al. An updated review of glucocorticoid-related adverse events in patients with rheumatoid arthritis. Expert Opin Drug Saf. 2019;18(7):581-90. doi: 10.1080/14740338.2019.1615052

137. Petta I, Peene I, Elewaut D, et al. Risks and benefits of corticosteroids in arthritic diseases in the clinic. Biochem Pharmacol. 2019;165:112-25. doi: 10.1016/j.bcp.2019.04.009

138. Cohen SB, Pope J, Haraoui B, et al. Methotrexate withdrawal in patients with rheumatoid arthritis who achieve low disease activity with tofacitinib modified-release 11 mg once daily plus methotrexate (ORAL Shift): a randomized, phase 3b/4, non-inferiority trial. Lancet. 2019 Aug 06. doi: 10.1016/S2665-9913(19)30005-0

139. Cohen S, Pope J, Haraoui B, et al. Efficacy and Safety of Tofacitinib Modified-Release 11 Mg Once Daily + MTX in RA Patients with an Inadequate Response to MTX: Open-Label Phase Results from a Global Phase 3b/4 MTX Withdrawal Study [abstract]. Arthritis Rheum. 2019;71 Suppl 10.

140. Strand V, Pope J, Woolcott J, et al. MTX Withdrawal in Patients with RA Who Achieve Low Disease Activity with Tofacitinib Modified-Release 11 Mg Once Daily + MTX: An Assessment of the Impact on the Short Form-36 Patient-Reported Outcome [abstract]. Arthritis Rheum. 2019; 71 Suppl 10. Available from: https://acrabstracts.org/abstract/mtx-withdrawal-in-patients-with-ra-who-achieve-low-disease-activity-with-tofacitinib-modi-fied-release-11-mg-once-daily-mtx-an-assessment-of-the-impact-on-the-short-form-36-patient-reported-outcome/

141. Lamba M, Wang R, Fletcher T, et al. Extended-release once-daily formulation of tofacitinib: evaluation of pharmacokinetics compared with immediate-release tofacitinib and impact of food. J Clin Pharmacol. 2016;56:1362-71. doi: 10.1002/jcph.734

142. Lamba M, Hutmacher MM, Furst DE, et al. Model-informed development and registration of a once-daily regimen of extended-release tofacitinib. Clin Pharmacol Ther. 2017;101:745-53. doi: 10.1002/cpt.576

143. Tanaka Y, Sugiyama N, Toyoizumi S, et al. Modified- versus immediate-release tofacitinib in Japanese rheumatoid arthritis patients: a randomized, phase III, non-inferiority study. Rheumatology (Oxford). 2019;58(1):70-9. doi: 10.1093/rheumatol-ogy/key250

144. Van Vollenhoven RF, Lee EB, Fallon L, et al. Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Probability of Achieving Low Disease Activity at Month 6. Arthritis Care Res (Hoboken). 2019;71(1):71-9. doi: 10.1002/acr.23585

145. Aletaha D, Alasti F, Smolen JS. Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies for the 3-month time point. Ann Rheum Dis. 2016;75:1479-85. doi: 10.1136/annrheumdis-2015-208324

146. Aletaha D, Funovits J, Keystone EC, et al. Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum. 2007;56:3226-35. doi: 10.1002/art.22943

147. Van der Heijde D, Keystone EC, Curtis JR, et al. Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post-hoc analysis of the RAPID 1 trial. J Rheumatol. 2012;39:1326-33. doi: 10.3899/jrheum.111171

148. Kawashiri SY, Nishino A, Suzuki T, et al. Rapid improvement of clinical disease activity index (CDAI) at 3 months predicts a preferable CDAI outcome at 1 year in active rheumatoid arthritis patients treated with tocilizumab: results from an observational investigation of daily clinical practice. Clin Exp Rheumatol. 2016;34:808-12.

149. Norvang V, Sexton J, Kristianslund EK, et al. Predicting achievement of the treatment targets at 6 months from 3-month response levels in rheumatoid arthritis: data from real-life follow-up in the NOR-DMARD study. RMD Open. 2018;4(2):e000773. doi: 10.1136/rmdopen-2018-0007

150. Conaghan PG, Оstergaard M, Troum O, et al. Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis. Arthritis Res Ther. 2019;21(1):214. doi: 10.1186/s13075-019-2000-1

151. Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016 Jan;75(1):3-15. doi: 10.1136/annrheumdis-2015-207524

152. Van Vollenhoven R. Treat-to-target in rheumatoid arthritis — are we there yet? Nat Rev Rheumatol. 2019;15(3):180-6. doi: 10.1038/s41584-019-0170-5

153. Bird P, Hall S, Nash P, et al. Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib. RMD Open. 2019;5(1):e000742. doi: 10.1136/rmdopen-2018-0007

154. Fleischmann RM, Huizinga TW, Kavanaugh AF, et al. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis. RMD Open. 2016;2:e000262. doi: 10.1136/rmdopen-2016-000262

155. Takeuchi T, Tanaka Y, Sugiyama N, et al. Efficacy of Tofacitinib Monotherapy, Tofacitinib with Methotrexate and Adalimumab with Methotrexate in Patients with Early (<2 Years) vs Established (>2 Years) Rheumatoid Arthritis: A Post Hoc Analysis of Data from ORAL Strategy [abstract]. Arthritis Rheum. 2019;71 Suppl 10. Available from: https://acrabstracts.org/abstract/efficacy-of-tofaci-tinib-monotherapy-tofacitinib-with-methotrexate-and-adalimum-ab-with-methotrexate-in-patients-with-early-%e2%89%a4-2-years-vs-established-2-years-rheumatoid-arthritis-a-p/

156. Schwartzman S, van Vollenoven R, Matsumoto A, et al. Efficacy of tofacitinib in patients with moderate to severe rheumatoid arthritis by baseline-C-reactive proteins levels and erythrocyte sedimentation rate. Ann Rheum Dis. 2018. doi: 10.1136/annrheumdis-2018-eular.2676

157. Favalli EG, Bugatti S, Biggioggero M, Caporali R. Treatment comparison in rheumatoid arthritis: head-to-head trials and innovative study designs. BiomedRes Int. 2014;2014:831603. doi: 10.1155/2014/831603

158. Buch MH, Pavitt S, Parmar M, Emery P. Creative trial design in RA: optimizing patient outcomes. Nat Rev Rheumatol. 2013;9(3):183-94. doi: 10.1038/nrrheum.2013.5

159. Pincus T, Bergman MJ, Yazici Y. Limitations of clinical trials in chronic diseases: is the efficacy of methotrexate (MTX) underestimated in polyarticular psoriatic arthritis on the basis of limitations of clinical trials more than on limitations of MTX, as was seen in rheumatoid arthritis? Clin Exp Rheumatol. 2015;33(5 Suppl 93):S82-93.

160. Eichler HG, Abadie E, Breckenridge A, et al. Bridging the efficacy-effectiveness gap: a regulator's perspective on addressing variability of drug response. Nat Rev Drug Discov. 2011;10:495-506. doi: 10.1038/nrd3501

161. Nasonov EL, Karateev DE, Satybaldyev AM, et al. Rheumatoid arthritis in the Russian Federation according to Russian Arthritis Registry Data (Communication I). Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(5):472-84 (In Russ.). doi: 10.14412/1995-4484-2015-472-484

162. Nikiphorou E, Buch MH, Hyrich KL. Biologics registers in RA: methodological aspects, current role and future applications. Nat Rev Rheumatol. 2017 Aug;13(8):503-10. doi: 10.1038/nrrheum.2017.81

163. Finckh A, Courvoisier D. Lessons learned from rheumatoid arthritis registries. Joint Bone Spine. 2018 May;85(3):271-4. doi: 10.1016/j.jbspin.2017.12.005

164. Pombo-Suarez M, Gomez-Reino J. The role of registries in the treatment of rheumatoid arthritis with biologic disease-modifying anti-rheumatic drugs. Pharmacol Res. 2019 Oct;148:104410. doi: 10.1016/j.phrs.2019.104410

165. Monti S, Grosso V, Todoerti M, Caporali R. Randomized controlled trials and real-world data: differences and similarities to untangle literature data. Rheumatology (Oxford). 2018 Oct 1;57 (57 Suppl 7):vii54-vii58. doi: 10.1093/rheumatology/key109

166. Caporali R, Zavaglia D. Real-world experience with tofacitinib for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2019;37:485-95.

167. Harnett J, Gerber R, Gruben D, et al. Evaluation of real-world ex perience with tofacitinib compared with adalimumab, etanercept, and abatacept in RA patients with 1 previous biologic DMARD: Data from a U.S. Administrative Claims Database. JManag Care Spec Pharm. 2016;22:1457-71. doi: 10.18553/jmcp.2016.22.12.1457

168. Smith T, Harnett J, Gruben D, et al. Real-world ex perience with tofacitinib versus adalimumab and etanercept in biologic-naive patients with RA previously treated with methotrexate: Data from a US Administrative Healthcare Insurance Claims Database. Arthritis Rheum. 2017;69(S10):abstract 2831.

169. Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis. Rheumatol Ther. 2019 Nov 9. doi: 10.1007/s40744-019-00177-4

170. Kavanaugh A, Reed GW, Saunders KC, et al. Clinical characteristics of RA patients newly prescribed tofacitinib citrate (tofaci-tinib) in the United States after food and drug administration approval: results from the CORRONA US rheumatoid arthritis registry. Ann Rheum Dis. 2015;74:1041. doi: 10.1136/annrheumdis-2015-eular.1760

171. Kavanaugh AF, Geier J, Bingham CI, et al. Real world results from a post-approval safety surveillance of tofacitinib (Xeljanz): Over 3 year results from an ongoing US- based rheumatoid arthritis registry. Arthritis Rheum. 2016;68(S10):abstract 2595.

172. Mori S, Yoshitama T, Ueki Y. Tofacitinib therapy for rheumatoid arthritis: A direct comparison study between biologic-naive and experienced patients. Intern Med. 2018;57:663-70. doi: 10.2169/internalmedicine.9341-17

173. Iwamoto N, Tsuji S, Tanakatani A, et al. Efficacy and safety at 24 weeks of daily clinical use of tofacitinib in patients with rheumatoid arthritis. PLoSOne. 2017;12:e0177057. doi: 10.1371/journal.pone.0177057

174. Finckh A, Herzog L, Scherer A. Drug retention of tofacitinib versus biologic antirheumatic agents in rheumatoid arthritis: observational data from the Swiss SCQM registry. Ann Rheum Dis. 2017;76 Suppl. 2:267. doi: 10.1136/annrheumdis-2017-eular.6804

175. Meissner V, Baganz L, Schneider M, et al. Baricitinib and tofaci-tinib in real life-does obesity impact response to Janus kinase inhibitor therapy in rheumatoid arthritis? Arthritis Rheum. 2018;70 Suppl 10:abstract 1518.

176. Pope J, Bessette L, Jones N, et al. Experience with tofacitinib in Canada: patient characteristics and treatment patterns in rheumatoid arthritis over 3 years. Rheumatology (Oxford). 2019 Aug 13. doi: 10.1093/rheumatology/kez324

177. Choquette D, Bessette L, Brown J, et al. Tofacitinib show similar retention when used with and without methotrexate. Analysis from Rhumadata® Clinical Database and Registry. Arthritis Rheum. 2018;70 Suppl 10:abstract 1531.

178. Marshall AC, Bowen K, Starner CI, Gleason PP. Tofacitinib (Xeljanz) utilization patterns and persistency among 4.4 million continuously enrolled commercially insured members over 4 years. AMCPNexus. 2016; Poster 18349.

179. Movahedi M, Cesta A, Li X, et al, Other OBRI Investigators A. Time to Discontinuation of Tofacitinib in Rheumatoid Arthritis Patients with and Without Methotrexate: Results from a Rheumatoid Arthritis Cohort [abstract]. Arthritis Rheum. 2019;71 Suppl 10. Available from: https://acrabstracts.org/abstract/time-to-discontinuation-of-tofacitinib-in-rheumatoid-arthritis-patients-with-and-without-methotrexate-results-from-a-rheuma-toid-arthritis-cohort/

180. Mueller RB, Hasler C, Popp F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10). doi: 10.3390/jcm8101548

181. Machado MAA, Moura CS, Guerra SF, et al. Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study. Arthritis Res Ther. 2018;20(1):60. doi: 10.1186/s13075-018-1539-6

182. Croiteru A, Lidar M, Reitblat T, et al. Real Life Retention of Tofacitinib in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheum. 2019;71 Suppl 10. Available from: https://acrab-stracts.org/abstract/real-life-retention-of-tofacitinib-in-patients-with-rheumatoid-arthritis/

183. Bird P, Littlejohn G, Butcher B, et al. Evaluation of Effectiveness and Usage Patterns of Tofacitinib in Treatment of Rheumatoid Arthritis in Australia: An Analysis from the OPAL-QUMI Real World Dataset [abstract]. Arthritis Rheum. 2019;71 Suppl 10. Available from: https://acrabstracts.org/abstract/evaluation-of-effectiveness-and-usage-patterns-of-tofacitinib-in-treatment-of-rheuma-toid-arthritis-in-australia-an-analysis-from-the-opal-qumi-real-world-dataset/

184. Harnett J, Smith T, Woolcott J, et al. Impact of TNF Inhibitor Cycling with Adalimumab and Etanercept vs Switching to Tofacitinib [abstract]. Arthritis Rheum. 2019;71 Suppl 10. Available from: https://acrabstracts.org/abstract/impact-of-tnf-inhibitor-cycling-with-adalimumab-and-etanercept-vs-switch-ing-to-tofacitinib/

185. Stamp LK, Chan SJ, Marra C, et al. Tapering biologic therapy for people with rheumatoid arthritis in remission: A review of patient perspectives and associated clinical evidence. Musculoskeletal Care. 2019;17(3):161-9. doi: 10.1002/msc.1404

186. Schett G, Emery P, Tanaka Y, et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016;75(8):1428-37. doi: 10.1136/annrheumdis-2016-209201

187. Kubo S, Yamaoka K, Amano K, et al. Discontinuation of tofaci-tinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study. Rheumatology (Oxford). 2017;56(8):1293-301. doi: 10.1093/rheumatology/kex068

188. Perez-Roman DI, Ortiz-Haro AB, Ruiz-Medrano E, et al. Outcomes after rheumatoid arthritis patients complete their participation in a long-term observational study with tofacitinib combined with methotrexate: practical and ethical implications in vulnerable populations after tofacitinib discontinuation. RheumatolInt. 2018;38(4):599-606. doi: 10.1007/s00296-017-3910-3

189. Mori S, Ueki Y. Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study. Clin Rheumatol. 2019 Aug 9. doi: 10.1007/s10067-019-04721-z

190. Kaine J, Tesser J, DeMasi R, et al. Efficacy of tofacitinib after temporary discontinuation in patients with rheumatoid arthritis: analysis of Data from open-label long-term extension studies. Ann Rheum Dis. 2018. doi: 10.1136/annrheumdis-2018-eular.3755

191. Takeuchi T, Genovese MC, Haraoui B, et al. Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study. Ann Rheum Dis. 2019;78(2):171-8. doi: 10.1136/annrheumdis-2018-213271

192. Atzeni F, Masala IF, di Franco M, Sarzi-Puttini P. Infections in rheumatoid arthritis. Curr Opin Rheumatol. 2017;29(4):323-30. doi: 10.1097/BOR.0000000000000389

193. Kivitz AJ, Cohen S, Keystone E, et al. A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population. Semin Arthritis Rheum. 2018;48(3):406-15. doi: 10.1016/j.semarthrit.2018.07.006

194. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017;13(5):320. doi: 10.1038/nrrheum.2017.51

195. Harigai M. Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford). 2019;58 Suppl 1:i34-i42. doi: 10.1093/rheumatology/key287

196. Charles-Schoeman C, DeMasi R, Valdez H, et al. Risk Factors for Major Adverse Cardiovascular Events in Phase III and LongTerm Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis. Arthritis Rheum. 2019;71(9):1450-9. doi: 10.1002/art.40911

197. Xie W, Huang Y, Xiao S, et al. Impact of Janus kinase inhibitors on risk of cardiovascular events in patients with rheumatoid arthritis: systematic review and meta-analysis of randomised controlled trials. Ann Rheum Dis. 2019;78(8):1048-54. doi: 10.1136/annrheumdis-2018-214846

198. Nurmohamed M, Choy E, Lula S, et al. The Impact of Biologics and Tofacitinib on Cardiovascular Risk Factors and Outcomes in Patients with Rheumatic Disease: A Systematic Literature Review. Drug Saf. 2018;41(5):473-88. doi: 10.1007/s40264-017-0628-9

199. Charles-Schoeman C, Fleischmann R, Davignon J, et al. Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib. Arthritis Rheum. 2015;67(3):616-25. doi: 10.1002/art.38974

200. McInnes IB, Kim HY, Lee SH, et al. Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann Rheum Dis. 2014;73(1):124-31. doi: 10.1136/annrheumdis-2012-2024

201. Kume K, Amano K, Yamada S, et al. Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study. Rheumatol Int. 2017;37(12):2079-85. doi: 10.1007/s00296-017-3844-9

202. Luisse A, Pierini F, Gandino I, et al. Effect of tofacitinib on the qualityve profile of high density lipoproteins molecules in patients with rheumatoid arthritis. Arthritis Rheum. 2019;71 Suppl 10:abstract 1415.

203. Schulze-Koops H, Strand V, Nduaka C, et al. Analysis of haemato-logical changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies. Rheumatology (Oxford). 2017;56(1):46-57. doi: 10.1093/rheumatology/kew329

204. Mariette X, Chen C, Biswas P, et al. Lymphoma in the tofacitinib rheumatoid arthritis clinical development program. Arthritis Care Res (Hoboken). 2017. doi: 10.1002/acr.23421

205. Curtis JR, Lanas A, John A, et al. Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(12):1819-28. doi: 10.1002/acr.21764

206. Charles-Schoeman C, Burmester G, Nash P, et al. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178

207. Winthrop KL, Curtis JR, Lindsey S, et al. Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy. Arthritis Rheum. 2017;69(10):1960-8. doi: 10.1002/art.40189

208. Curtis JR, Xie F, Bernatsky S, et al. Herpes zoster in tofacitinib users with and without concomitant methotrexate and glucocorticoids. Arthritis Rheum. 2019;70 Suppl 10:abstract 665.

209. Desai RJ, Pawar A, Weinblatt ME, Kim SC. Comparative Risk of Venous Thromboembolism in Rheumatoid Arthritis Patients Receiving Tofacitinib Versus Those Receiving Tumor Necrosis Factor Inhibitors: An Observational Cohort Study. Arthritis Rheum. 2019;71(6):892-900. doi: 10.1002/art.40798

210. Weinblatt MTP, Burmester GR, Witt S, et al. Cardiovascular safety during treatment with baricitinib in rheumatoid arthritis [abstract]. Arthritis Rheum. (Hoboken, NJ). 2017;69 Suppl 10.

211. Kim SC, Schneeweiss S, Liu J, Solomon DH. Risk of venous thromboembolism in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65:1600-7. doi: 10.1002/acr.22039

212. Clowse MEB, Feldman SR, Isaacs JD, et al. Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf. 2016;39(8):755-62. doi: 10.1007/s40264-016-0431-z

213. He Y, Wong AYS, Chan EW, et al. Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systemic review and meta-analysis. BMCMusculoskelet Disord. 2013;14:298. doi: 10.1186/1471-2474-14-298

214. Berhan A. Efficacy, safety and tolerability of tofacitinib in patients with an inadequate response to disease modifying anti-rheumatic drugs: a meta-analysis of randomized double-blind controlled studies. BMC Musculoskelet Disord. 2013;14:332. doi: 10.1186/147-2474-14-332

215. Kawalec P, Mikrut A, Wisniewska N, Pilc A. The effectiveness of tofacitinib, a novel Janus kinase inhibitor. In the treatment of rheumatoid arthritis: a systemic review and metha-analysis. Clin Rheumatol. 2013;32:1414-24. doi. 10.1007/s10067-013-2329-9

216. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2016 May 13;(5):CD012183. doi: 10.1002/14651858.CD012183

217. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA). Cochrane Database Syst Rev. 2016 Nov 17;11:CD012437. doi: 10.1002/14651858.CD012437

218. Singh JA, Hossain A, Mudano AS, et al. Biologics or tofacitinib for people with rheumatoid arthritis naive to methotrexate: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2017;5:CD012657. doi: 10.1002/14651858.CD012657

219. Singh JA, Hossain A, Tanjong Ghogomu E, et al. Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network metaanalysis. Cochrane Database Syst Rev. 2017;3:CD012591. doi: 10.1002/14651858.CD012591

220. Bergrath E, Gerber RA, Gruben D, et al. Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network MetaAnalysis. Int JRheumatol. 2017;2017:8417249. doi: 10.1155/2017/8417249

221. Camean-Castillo M, Gimeno-Ballester V, Rios-Sanchez E, et al. Network meta-analysis of tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients. J Clin Pharm Then. 2019;44(3):384-96. doi: 10.1111/jcpt.12795

222. Venerito V, Lopalco G, Cacciapaglia F, et al. A Bayesian mixed treatment comparison of efficacy of biologics and small molecules in early rheumatoid arthritis. Clin Rheumatol. 2019;38(5):1309-17. doi: 10.1007/s10067-018-04406-z

223. Huang F, Luo Z-C. Adverse drug events associated with 5 mg versus 10 mg tofacitinib (Janus kinase inhibitor) twice daily for the treatment of autoimmune diseases: a systemic review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2019;38:523-34. doi: 10.1007/s10067-018-4299-5

224. Song GG, Choi SJ, Lee YH. Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. Int J Rheum Dis. 2019;22(8):1563-71. doi: 10.1111/1756-185X.136

225. Jegatheeswaran J, Turk M, Pope JE. Comparison of Janus kinase inhibitors in the treatment of rheumatoid arthritis: a systemic literature review. Immunotherapy. 2019;11(8):737-54. doi: 10.2217/imt-2018-0178

226. Edwards C, Sawant R, Du E, et al. A matching-adjusted indirect comparison (MAIC) of upadacitinib versus tofacitinib in csDMARD-IR with moderate to severe rheumatoid arthritis. (RA). Ann Rheum Dis. 2019. doi: 10.1136/annrheumdis-2019-eular.7189

227. Dougados M, van der Heijde D, Chen Y, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017;76(1):88-95. doi: 10.1136/annrheumdis-2016-210094

228. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243-52. doi: 10.1056/NEJMoa1507247

229. Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheum. 2017;69(3):506-17.

230. Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652-62. doi: 10.1056/NEJMoa1608345

231. Genovese MC, Smolen JS, Weinblatt ME, et al. Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a Phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheum. 2016;68(12):2857-66. doi: 10.1002/art.39808

232. Burmester GR, Kremer JM, van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomized, double-blind, placebo-controlled Phase III trial. Lancet. 2018;391(10139):2503-12. doi: 10.1016/S0140-6736(18)31115-2

233. Kremer JM, Emery P, Camp HS, et al. A Phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to antitumor necrosis factor therapy. Arthritis Rheum. 2016;68(12):2867-77. doi: 10.1002/art.39801

234. Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomized controlled Phase III trial. Lancet. 2018;391(10139):2513-24. doi: 10.1016/S0140-6736(18)31116-4

235. Van Vollenhoven R, Takeuchi T, Pangan AL, et al. A Phase 3, Randomized, Controlled Trial Comparing Upadacitinib Monotherapy to MTX Monotherapy in MTX-Naive Patients with Active Rheumatoid Arthritis [abstract]. Arthritis Rheum. 2018;70 Suppl 10. doi: 10.1093/rheumatology/kez106.058

236. Fleischmann R, Pangan AL, Song IH, et al. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheum. 2019 Nov;71(11):1788-800. doi: 10.1002/art.41032

237. Tofacitinib: Summary of Product Characteristics. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004214/WC500224911.pdf

238. Smolen JS, Aletaha D, Gruben D, et al. Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria. Arthritis Rheum. 2017;69(4):728-34. doi: 10.1002/art.39996

239. Meissner Y, Baganz L, Schneider M, et al. Baricitinib and Tofacitinib in Real Life - Does Obesity Impact Response to Janus Kinase Inhibitor Therapy in Rheumatoid Arthritis? [abstract]. Arthritis Rheum. 2018;70 Suppl 10.

240. Singh S, Facciorusso A, Singh AG, et al. Obesity and response to anti-tumor necrosis factorа agents in patients with select immune-mediated inflammatory diseases: A systematic review and meta-analysis. PLoSOne. 2018;13(5):e0195123. doi: 10.1371/journal.pone.0195123

241. Rigby WFC, Lampl K, Low JM, Furst DE. Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs. Int J Rheumatol. 2017;2017:9614241. doi: 10.1155/2017/9614241

242. Calabrese LH, Abud-Mendoza C, Lindsey SM, et al. Live Zoster Vaccine in Patients with Rheumatoid Arthritis Treated with Tofacitinib with or without Methotrexate, or Adalimumab with Methotrexate. Arthritis Care Res (Hoboken). 2019 Jun 17. doi: 10.1002/acr.24010

243. Winthrop KL, Silverfield J, Racewicz A, et al. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis. 2016;75:687-95. doi: 10.1136/annrheumdis-2014-207191

244. Goodman SM, Springer B, Guyatt G, et al. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Rheum. 2017;69:1538-51. doi: 10.1002/art.40149

245. Gremese E, Alivernini S, Tolusso B, et al. JAK inhibition by methotrexate (and csDMARDs) may explain clinical efficacy as monotherapy and combination therapy. J Leukoc Biol. 2019;106(5):1063-8. doi: 10.1002/JLB.5RU0519-145R

246. Kronzer VL, Crowson CS, Sparks JA, et al. Family history of rheumatologic, autoimmune, and non-autoimmune diseases and risk of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2019 Nov 30. doi: 10.1002/acr.24115

247. Emamifar A, Jensen Hansen IM. The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency and other comorbid autoimmune diseases on treatment outcome in patients with rheumatoid arthritis: An exploratory cohort study. Medicine (Baltimore). 2018;97(21):e10865. doi: 10.1097/MD.0000000000010865


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Nasonov E.L., Avdeeva A.S., Lila A.M. Efficacy and safety of tofacitinib for immune-mediated inflammatory rheumatic diseases (Part I). Rheumatology Science and Practice. 2020;58(1):62-79. (In Russ.) https://doi.org/10.14412/1995-4484-2020-62-79

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