Барицитиниб – основные результаты многолетнего использования при ревматоидном артрите

В обзоре представлены последние данные о длительном применении селективного ингибитора Янус-киназ (иJAK) барицитиниба (БАРИ) у больных ревматоидным артритом (РА) в реальной клинической практике. Результаты многолетнего (до 9,5 года) использования БАРИ при РА свидетельствуют о том, что по эффективности он сопоставим с генно-инженерными биологическими препаратами (ГИБП) и тофацитинибом или превосходит их, при этом препарат более эффективен у больных, не получавших ранее ГИБП или иJAK. Показана возможность при достижении цели терапии уменьшения дозы БАРИ до 2 мг/сут без потери эффекта у большинства пациентов и купирования обострения, возникшего на фоне уменьшенной дозы (или, при необходимости, перерыва в лечении), при возврате к полной дозе препарата. По данным регистров многих стран и открытых наблюдательных исследований, БАРИ обладает хорошей переносимостью при длительном применении, в том числе у пациентов старшего возраста, имеющих ≥1 фактор риска кардиоваскулярных заболеваний. Отмечена также высокая выживаемость терапии БАРИ, превышающая, по данным некоторых регистров, таковую ингибиторов фактора некроза опухоли α. На фоне приема БАРИ продемонстрировано быстрое (в течение 1–3 мес) статистически значимое уменьшение боли независимо от степени подавления активности заболевания, коррелирующее с улучшением функционального статуса и общего состояния больных. Показана также возможность подавления прогрессирования структурных повреждений у больных РА, что позволяет выбрать индивидуальную тактику ведения таких пациентов. 

1. Nash P, Kerschbaumer A, Dorner T, et al. Points to consider for the treatment of immunemediated inflammatory diseases with Janus kinase inhibitors: a consensus statement. Ann Rheum Dis. 2021 Jan;80(1):71-87. doi: 10.1136/annrheumdis-2020-218398. Epub 2020 Nov 6.

2. Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: Results from the RA-BUILD study. Ann Rheum Dis. 2017 Jan;76(1):88-95. doi: 10.1136/annrheumdis-2016-210094. Epub 2016 Sep 29.

3. 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.

4. 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 Rheumatol. 2017 Mar;69(3):506-517. doi: 10.1002/art.39953. /N

5. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247.

6. Smolen J, Landewe RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023 Jan;82(1):3-18. doi: 10.1136/ard-2022-223356. Epub 2022 Nov 10.

7. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020 Jun;2(6): e347-e357. doi: 10.1016/S2665-9913(20)30032-1.

8. Taylor PC, Laedermann C, Alten R, et al. A JAK Inhibitor for Treatment of Rheumatoid Arthritis: The Baricitinib Experience. J Clin Med. 2023 Jul 6;12(13):4527. doi: 10.3390/jcm12134527.

9. Van der Heijde D, Kartman CE, Xie L, et al. Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis – a comprehensive review. Arthritis Res Ther. 2021 Jan 4;23(1):3. doi: 10.1186/s13075-020-02379-6.

10. Caporali R, Aletaha D, Sanmartн R, et al. POS0701 Long-term efficacy of baricitinib in patients with rheumatoid arthritis who have had inadequate response to csDMARDs: Results from RA-beyond up to 7 years of treatment. Ann Rheum Dis. 2022;81(Suppl.1): 630–631. doi: 10.1136/annrheumdis-2022-eular.4546

11. Emery P, Tanaka Y, Cardillo T, et al. Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis. Arthritis Res Ther. 2020 May 15; 22(1):115. doi: 10.1186/s13075-020-02199-8.

12. Fraenkel L, Bathon JM, Bryant R, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021 Jul;73(7):924-939. doi: 10.1002/acr.24596. Epub 2021 Jun 8.

13. 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 Feb;78(2):171-178. doi: 10.1136/annrheumdis-2018-213271. Epub 2018 Sep 7.

14. Alten R, Burmester GR, Edwards CE, et al. POS0848. Discontinuation and effectiveness of baricitinib in rheumatoid arthritis according to patient age and prior treatment: 2-year data from the European cohort of the RA-BE-REAL study. Ann Rheum Dis. 2023; 82(suppl1):724-725. doi: 10.1136/annrheumdis-2023-eular.2554

15. Voshaar MO, Klooster PT, Tedjo D, et al. Baricitinib versus TNF-inhibitors in patients with active rheumatoid arthritis and an inadequate response to csDMARDS: 12 weeks results of a pragmatic, multicenter, open label, noninferiority trial. Ann Rheum Dis. 2023; 82(Suppl 1):713. doi:10.1136/annrheumdis2023-eular.4317

16. Edwards CJ, Mount J, Meeks A, et al. Characteristics of patients initiating treatment with baricitinib and outcomes at follow-up: analysis of BSRBR-RA Registry data. Rheumatology (Oxford). 2023 Oct 3;62(10): 3400-3408. doi: 10.1093/rheumatology/kead074.

17. Lauper K, Iudici M, Mongin D, et al. Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAKpot’ collaboration. Ann Rheum Dis. 2022 Oct;81(10):1358-1366. doi: 10.1136/annrheumdis-2022-222586. Epub 2022 Jun 15.

18. Aymon R, Mongin D, Bergstra SA, et al. Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the ‘JAK-pot’ study). Ann Rheum Dis. 2024 Mar 12;83(4):421-428. doi: 10.1136/ard-2023-224670.

19. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022 Jan 27;386(4):316-326. doi: 10.1056/NEJMoa2109927.

20. Charles-Schoeman C, Buch MH, Dougados M, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL surveillance. Ann Rheum Dis. 2023 Jan;82(1):119-129. doi: 10.1136/ard-2022-222259. Epub 2022 Sep 22.

21. Kristensen LE, Danese S, Yndestad A, et al. Identification of two tofacitinib subpopulations with different relative risk versus TNF inhibitors: an analysis of the open label, randomised controlled study ORAL surveillance. Ann Rheum Dis. 2023 Jul;82(7):901-910. doi: 10.1136/ard-2022-223715. Epub 2023 Mar 17.

22. Aymon R, Mongin D, Bergstra SA, et al. Incidence of mayor adverse cardiovascular events in patients with rheumatoid arthritis treated with JAK-inhibitors compared to bDMARDs: data from an international collaboration of registries (the “JAK-POT” study). Ann Rheum Dis. 2023;82(Suppl 1): 143-145. doi: 10.1136/annrheumdis-2023-eular.660

23. Meissner Y, Albrecht R, Kekow J, et al. Risk of cardiovascular events under Janus kinase inhibitors in patients with rheumatoid arthritis: observational data from the German RABBIT register. Ann Rheum Dis. 2022; 81(Suppl 1):86-87. Doi: 10.1136/annrheumdis-2022-eular.779.

24. Hoisnard L, Vegas P, Dray-Pira R, et al. Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study. Ann Rheum Dis. 2023 Feb;82(2): 182-188. doi: 10.1136/ard-2022-222824. Epub 2022 Oct 5.

25. Barbulescu A, Askling J, Chatzidionysiou K, et al. Effectiveness of baricitinib and tofacitinib compared with bDMARDs in RA: results from a cohort study using nationwide Swedish register data. Rheumatology (Oxford). 2022 Oct 6;61(10):3952-3962. doi: 10.1093/rheumatology/keac068.

26. Gilbert B, Courvoisier D, Mongin D, et al. Real world effectiveness of baricitinib in the Swiss rheumatoid arthritis register (SCOM-RA). Ann Rheum Dis. 2021;80(Suppl 1):577-578. doi: 10.1136/annrheumdis-2021-eular.1781.

27. Guidelli GM, Viapiana O, Luciano N, et al. Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study. Clin Exp Rheumatol. 2021 Jul-Aug;39(4):868-873. doi: 10.55563/clinexprheumatol/pudtpo. Epub 2020 Dec 18.

28. Takagi M, Atsumi T, Matsuno H, et al. Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance. Mod Rheumatol. 2023 Jul 4;33(4):647-656. doi: 10.1093/mr/roac089.

29. Pope JE, Fleischmann RM. Jack pot! What can we learn about registries with respect to treatment cycling in rheumatoid arthritis? Ann Rheum Dis. 2023 Feb;82(2): 161-163. doi: 10.1136/ard-2022-223071. Epub 2023 Jan 6.

30. Pombo-Suarez M, Sanchez-Piedra C, Gomez-Reino J, et al. After JAK inhibitor failure: to cycle or to switch, that is the question – data from the JAK-pot collaboration of registries. Ann Rheum Dis. 2023 Feb;82(2): 175-181. doi: 10.1136/ard-2022-222835. Epub 2022 Sep 13.

31. Perrone V, Losi S, Rogai V, et al. Realworld analysis of therapeutic patterns in patients affected by rheumatoid arthritis in Italy: a focus on baricitinib. Rheumatol Ther. 2020 Sep;7(3):657-665. doi: 10.1007/s40744-02-00218-3. Epub 2020 Jul 18.

32. Perrone V, Losi S, Rogai V, et al. Treatment patterns and pharmacoutilization in patients affected by rheumatoid arthritis in Italian settings. Int J Environ Res Public Health. 2021 May 26;18(11):5679. doi: 10.3390/ijerph18115679.

33. Littlejohn G, Smith T, Tymms K, et al. THU0209 Uptake of Janus kinase inhibitors for management of rheumatoid arthritis in Australia. Ann Rheum Dis. 2020;79(Suppl 1):329. Doi: 10.1136/annrheumdis-2020-eular.5055.

34. Egeberg A, Rosenø NAL, Aagaard D, et al. Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis — a nationwide cohort study from the DANBIO and DERMBIO registries. Semin Arthritis Rheum. 2022 Apr:53:151979. doi: 10.1016/j.semarthrit.2022.151979. Epub 2022 Feb 9.

35. Gilbert B, Courvoisier D, Mongin D, et al. POS0668 Real world effectiveness of baricitinib in the Swiss Rheumatoid Arthritis Register (SCQM-RA). Ann Rheum Dis. 2021;80 (Suppl 1):577–578. doi:10.1136/annrheumdis-2021-eular.1781.

36. Takahashi N, Asai S, Kobayakawa T, et al. Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: Data from a Japanese multicenter registry. Sci Rep. 2020 Dec 14; 10(1):21907. doi: 10.1038/s41598-020-78925-8.

37. https://acrabstracts.org/abstract/a-multinational-prospective-observational-study-inpatients-with-rheumatoid-arthritis-receivingbaricitinib-targeted-synthetic-or-biologicdisease-modifying-therapies-6-month-effectiveness-and-pat/

38. Page J, Kearsley-Fleet L, Davies R, et al. AB0434 Early experience with JAK inhibitor prescribing in the uk: results from the British Society For Rheumatology Biologics Register For Rheumatoid Arthritis (BSRBR-RA). Ann Rheum Dis. 2019;78(Suppl 2):1680. doi:10.1136/annrheumdis-2019-eular.508.

39. Rosas J, Senabre-Gallego JM, Soler GS, et al. AB0442 Response to baricitinib in patients with rheumatoid arthritis with failure to conventional synthetic DMARD and/or biological DMARD: data from a local registry. Ann Rheum Dis. 2019;78 (Suppl 2):1684. doi:10.1136/annrheumdis-2019-eular. 3820.

40. Ciciriello S, Littlejohn G, Treuer T, et al. Comparative Effectiveness of First-Line Baricitinib in Patients With Rheumatoid Arthritis in the Australian OPAL Data Set. ACR Open Rheumatol. 2023 Jul;5(7):345-353. doi: 10.1002/acr2.11577. Epub 2023 Jun 12.

41. Hernandez-Cruz B, Kiltz U, Avouac J, et al. Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis. Rheumatol Ther. 2023 Dec;10(6):1417-1457. doi: 10.1007/s40744-023-00591-9. Epub 2023 Sep 16.

42. Alten R, Burmester GR, Matucci Cerinic M, et al. POS0666 A multinational, prospective, observational study in patients with rheumatoid arthritis receiving baricitinib, targeted synthetic or biologic disease-modifying therapies: 12 month time to discontinuation, effectiveness and patient reported outcome data from the European cohort. Ann Rheum Dis. 2022;81(Suppl 1):606–607. doi:10.1136/annrheumdis-2022-eular.265.

43. Baldi C, Falsetti P, Conticini E, et al. POS0661 Rapid response to baricitinib in patients with rheumatoid arthritis and an inadequate response to methotrexate and at least one biologic DMARD: a clinical and power doppler ultrasound study. Ann Rheum Dis. 2021;80(Suppl 1):573. doi10.1136/annrheumdis-2021-eular.1007.

44. Taylor PC, Lee YC, Fleischmann R, et al. Achieving Pain Control in Rheumatoid Arthritis with Baricitinib or Adalimumab Plus Methotrexate: Results from the RA-BEAM Trial. J Clin Med. 2019 Jun 12;8(6):831. doi: 10.3390/jcm8060831.

45. Deprez V, Le Monnier L, Sobhy-Danial JM, et al. Therapeutic maintenance of baricitinib and tofacitinib in real life. J Clin Med. 2020 Oct 16;9(10):3319. doi: 10.3390/jcm9103319.

46. Torikai E, Suzuki D. THU0196 Efficacy and safety up to 24 weeks of baricitinib for Japanese patients with rheumatoid arthritis in real world multicenter clinical data. Ann Rheum Dis. 2019;78(Suppl 2):375-6. doi: 10.1136/annrheumdis-2019-eular.4496

47. Cometi L, Bruni C, Tofani L, et al. AB0256 Baricitinib (BARI) versus biologics impact on steroid tapering in rheumatoid arthritis (RA). Ann Rheum Dis. 2021;80(Suppl 1): 1154-5. doi:10.1136/annrheumdis-2021-eular. 1343.

48. Yoshii I, Sawada N, Chijiwa T. AB0383 Comparison of efficacy and safety in jak inhibitor due to a difference of selectivity — tofacitinib vs baricitinib. Ann Rheum Dis. 2022;81(Suppl 1):1318-1319. doi:10.1136/annrheumdis-2022-eular.129

49. Torikai E, Hirano Y, Suzuki D, Kanayama Y. FRI0137 Discontinuation of baricitinib after achieving low disease activity in patients with rheumatoid arthritis in clinical practice; a multicenter observational study. Ann Rheum Dis. 2020;79(Suppl 1):651. doi:10.1136/annrheumdis-2020-eular.1546.

50. Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010 Apr;69(4):631-7. doi: 10.1136/ard.2009.123919. Epub 2010 Mar 9.

51. Sepriano A, van Dijk B, Ramiro S, et al. Distinction and prognosis of early arthritis phenotypes: an analysis in three European cohort. RMD Open. 2023 Nov;9(4):e003611. doi: 10.1136/rmdopen-2023-003611.

52. Lopez-Romero P, de la Torre I, Haladyj E, et al. Baricitinib further enhances diseasemodifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 May;81(5):622-631. doi: 10.1136/annrheumdis-2021-221323. Epub 2022 Feb 22.