Difficult-to-treat rheumatoid arthritis in the clinical practice of a rheumatological hospital. First look

Objective: to compare the course of the disease and therapy in rheumatoid arthritis (RA) patients who meet and do not meet the criteria for difficult- to-treat RA (D2T).

Patients and methods. The study included RA patients who met the 2010 ACR/EULAR criteria and who were hospitalized in the V.A. Nasonova Research Institute of Rheumatology from March to October 2021. All patients underwent a conventional clinical and laboratory examination, radiography of the hands and distal feet, and the radiological stage of RA according to Steinbroker was assessed. To determine the inflammatory activity, the DAS28-ESR and DAS28-CRP indices were calculated.

Results and discussion. The study included 303 patients with RA, 25 (8.4%) of them had D2T RA. The duration of RA in the D2T group was significantly longer than in other patients (15.9±11.8 and 11.9±9 years, respectively; p=0.04). X-ray changes in the joints in D2T were more pronounced. Patients with D2T had higher inflammatory activity at the time of hospitalization than patients who had continued prior therapy with biologic/targeted synthetic DMARDs. The dose of glucocorticoids (GC) in patients with D2T RA was higher compared to patients of other groups: on average 8.3±5.1 and 6.4±2.9 mg/day, respectively (p=0.02).

Conclusion. The results of this study suggest that in Russia, as well as abroad, the treat-to-target principle has not yet become widespread, and the selection of adequate therapy takes too much time. At the same time, Russian rheumatologists primarily use GC to suppress inflammatory activity. The introduction of modern recommendations for the management of patients with RA into routine clinical practice, could possibly restrain the formation of D2T RA.

1. Nasonov EL, Aleksandrova EN, Novikov AA. Autoimmune rheumatic diseases – problems of immunopathology and personalized therapy. Vestnik Rossiiskoi akademii meditsinskikh nauk. 2015;70(2):169-82. (In Russ.).

2. Erdes ShF, Galushko EA. Medical and social significance of joint and spine pathology among the adult population of the Russian Federation. Bol'. 2009;(3):19. (In Russ.).

3. Nasonov EL, Lila AM. Efficacy and safety of upadacitinib in rheumatoid arthritis. Nauchno-Prakticheskaya Revmatologiya. 2020;58(5):532-43. (In Russ.).

4. Kotovskaya MA, Nikishina NYu, Olyunin YuA. Strategy for dose reduction and discontinuation of biological agents in rheumatoid arthritis remission. Nauchno-Prakticheskaya Revmatologiya. 2018;56(1):99-106. (In Russ.).

5. Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical recommendations. Rheumatology.]. Moscow: GEOTAR-Media; 2020. 448 p..

6. Nasonov EL. New guidelines for the management of rheumatoid arthritis (EULAR, 2013): The place of glucocorticoids. Nauchnoprakticheskaya revmatologiya. 2013;53(3):238-50. (In Russ.).

7. Lila AM, Olyunin YuA, Gordeev AV. Assessing the status of patients with rheumatoid arthritis: modern tendencies. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2020;14(2):7-13 (In Russ.). doi: 10.14412/1996-7012-2020-2-7-13

8. Nasonov EL, Olyunin YuA, Lila AM. Rheumatoid arthritis: the problems of remission and therapy resistance. Nauchno-Prakticheskaya Revmatologiya. 2018;56(3):263-71. (In Russ.).

9. Gordeev AV, Olyunin YuA, Galushko EA, et al. Difficult-to-treat rheumatoid arthritis. What is it? Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2021;15(5): 7-11. (In Russ.). doi: 10.14412/1996-7012-2021-5-7-11

10. Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-5. doi: 10.1136/annrheumdis-2020-217344.

11. Nasonov EL, Lila AM, Mazurov VI, et al. Coronavirus Disease 2019 (COVID-19) and Immune-mediated Rheumatic Diseases. Recommendations of the Association of Rheumatologists of Russia. Nauchno-prakticheskaya revmatologiya. 2021;59(3):239-54. (In Russ.).

12. Messelink MA, Roodenrijs NMT, van Es B, et al. Identification and prediction of difficultto-treat rheumatoid arthritis patients in structured and unstructured routine care data: results from a hackathon. Arthritis Res Ther. 2021 Jul 8;23(1):184. doi: 10.1186/s13075-021-02560-5.

13. Watanabe R, Hashimoto M, Murata K, et al. Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort. Immunol Med. 2021 May 25:1-10. doi: 10.1080/25785826.2021.1928383

14. Takanashi S, Kaneko Y, Takeuchi T. Characteristics of patients with difficult-totreat rheumatoid arthritis in clinical practice. Rheumatology (Oxford). 2021 Nov 3;60(11):5247-56. doi: 10.1093/rheumatology/keab209

15. Roodenrijs NMT, van der Goes MC, Welsing PMJ, et al. Difficult-to-treat rheumatoid arthritis: contributing factors and burden of disease. Rheumatology (Oxford). 2021 Aug 2; 60(8):3778-88. doi: 10.1093/rheumatology/keaa860.

16. Roodenrijs NMT, van der Goes MC, Welsing PMJ, et al. Non-adherence in difficultto-treat rheumatoid arthritis from the perspectives of patients and rheumatologists: a concept mapping study. Rheumatology (Oxford). 2021 Nov 3;60(11):5105-16. doi: 10.1093/rheumatology/keab130.

17. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021 Jul; 73(7):1108-23. doi: 10.1002/art.41752.

18. Smolen JS, Landewй RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685-99. doi: 10.1136/annrheumdis-2019-216655.

19. Benham H, Chiu H, Tesiram J, et al. A patient-centered knowledge translation tool for treat-to-target strategy in rheumatoid arthritis: Patient and rheumatologist perspectives. Int J Rheum Dis. 2021 Mar;24(3):355-63. doi: 10.1111/1756-185X.14051.

20. Batko B, Batko K, Krzanowski M, Zuber Z. Physician Adherence to Treat-to-Target and Practice Guidelines in Rheumatoid Arthritis. J Clin Med. 2019 Sep 8;8(9):1416. doi: 10.3390/jcm8091416.

21. Lila AM, Gordeev AV, Olyunin YuA, Galushko EA. Multimorbidity in rheumatology. From comprehensive assessment of disease to evaluation of a set of diseases. Sovremennaya Revmatologiya = Modern Rheumatology Journal. 2019;13(3):4-9. (In Russ.). doi: 10.14412/1996-7012-2019-3-4-9

22. Folomeeva OM, Nasonov EL, Andrianova IA, et al. Assessment of the functional state of the population of Russian patients with rheumatoid arthritis according to the RAISER study. Nauchno-prakticheskaya revmatologiya. 2010; 48(3):15-22. (In Russ.).

23. Cai YM, Li R, Ye H, et al. Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis: a 5-year real-world consecutive study. Chin Med J (Engl). 2020 Jun 20;133(12):1397-403. doi: 10.1097/CM9.0000000000000811.

24. Nekvindova L, Vencovsky J, Pavelka K, et al. Switching first-line targeted therapy after not reaching low disease activity within 6 months is superior to conservative approach: a propensity score-matched analysis from the ATTRA registry. Arthritis Res Ther. 2021 Jan 6;23(1):11. doi: 10.1186/s13075-020-02393-8.

25. Harrold LR, Reed GW, John A, et al. Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2018 Mar;70(3):379-87. doi: 10.1002/acr.23294.

26. Karateev DE, Luchikhina EL, Demidova NV, et al. The first Russian strategic study of pharmacotherapy for rheumatoid arthritis (REMARCA trial): Results of 12-month treatment in 130 patients. Nauchno-prakticheskaya revmatologiya. 2014;52(6):607-14. (In Russ.).