Rheumatoid arthritis in real clinical practice: initiation of therapy with biological agents. Results of the «Computer Terminals of Self-Assessment for Patients with Rheumatic Diseases» («TERMINAL-II») project

Objective: to assess quality-of-life (QoL) dynamics in patients with rheumatoid arthritis (RA) when initiating therapy with biological agents (BAs) in real clinical practice.

Patients and methods. The investigation enrolled patients with RA from the patient cohort participating in the TERMINAL-II multicenter Russian study, who newly initiated BA therapy. In the self-assessment terminal, the patient completed HAQ, EQ-5D, and RAPID-3 questionnaires. DAS28, SDAI, CDAI, and RAPID-3 were used to determine disease activity. The patient's functional status and QoL were assessed using the HAQ index and the EQ-5D questionnaire, respectively. The efficiency of the therapy was analyzed 6 months after the start of the study according to the standard procedures.

Results and discussion. The investigation enrolled 156 RA patients: 79.6% females; mean age, 45.8±13.2 years; disease duration, 7.6±5.6 years. The patients had high RA activity (a mean DAS28 of 5.2±1.2, a mean SDAI of 39.5±16.4, a mean CDAI of 27.5±10.4, and a mean RAPID-3 of 15.1±3.6) and previous inefficacy of synthetic disease-modifying antirheumatic drugs (DMARDs) after at least 6 months of therapy. Only 1.2% of patients had a good functional status comparable to the population-based control (HAQ 40.5). 70% of patients needed to take non-steroidal anti-inflammatory drugs (NSAIDs). The first BA was chosen in accordance with the recommendations for administration of BAs and in terms of their availability in a specific region of the Russian Federation. The first prescribed BA was tumor necrosis factor-a (TNF-a) inhibitors in 112 (71.8%)patients, anti-B-cell therapy in 14 (9.0%), an interleukin-6 receptor inhibitor in 16 (10.3%), and a leukocyte costimulatory inhibitor in 14 (9.0%). Comparison of the patients receiving newly initiated therapy with TNF-a inhibitors and drugs with other mechanisms of action showed that the patients who had abatacept received higher doses of methotrexate (MTX), but lower doses of glucocorticoids (GCs) than those who were prescribed rituximab and tocilizumab. A statistically significant decrease in DAS28, SDAI, CDAI, and RAPID-3 scores was achieved after 6 months of therapy. Improvements of functional status and QoL in patients were also noted (p<0.0001). The patients continued to receive MTX. During the follow-up period, its dose remained almost unchanged: it averaged 15.7±3.8 and 15.7±3.7 mg/week at the beginning and the end of the study, respectively. Due to decreased inflammation, the dose of CS was reduced (on average, from 5.8±2.5 to 5.1±2.6 mg/day; p=0.02), the number of patients requiring NSAIDs declined (from 72.4 to 63.8%). DAS28, SDAI, and CDAI remission and low disease activity were achieved in 38.1, 16.5, and 20% of patients, respectively. The functional status improved in most patients with RA: 20, 50, and 70% improvements in HAQ were observed in 59.4, 46.9, and 28.7% of cases, respectively. QoL improvements were seen in two thirds of the patients: 30, 50, and 70% improvements in 58.3, 29.5, and in 23.7%. After 6-month follow-up, GC therapy was completely discontinued in 4.6% of patients; their dose was reduced in 5.3%, and 8.6% completely refused to take NSAIDs.

Conclusion. Biologic therapy was shown to be effective in RA patients with an inadequate response to synthetic NSAIDs in real clinical practice. The patients preferred the subcutaneous injection of BAs. Biologic treatment in most patients was initiated with TNF-a inhibitors, mainly with adalimumab. Six-month therapy could reduce disease activity and improve functional status and health-related QoL in two thirds of severe patients.

1. Nasonov EL, Karateev DE, Balabanova RM. Rheumatoid arthritis. In: Nasonov EL, Nasonova VA, editors. Revmatologiya. Natsional'noe rukovodstvo [Rheumatology. National guidelines]. Moscow: GEOTAR-Media; 2008. P. 290-331.

2. Nasonov EL. Rituximab. In: Nasonov EL, editor. Genno-inzhenernye biologicheskie preparaty v lechenii revmatoidnogo artrita [Genetically engineered biological drugs in the treatment of rheumatoid arthritis]. Moscow: IMA-PRESS; 2013. P. 200-21.

3. Nasonov EL, editor. Dostizheniya revmatologii v nachale XXI veka (k 60-letiyu Instituta revmatologii imeni VA.Nasonovoi) [Achievements of rheumatology in the early XXI century (to the 60th anniversary of the V.A. Nasonova Research Institute of Rheumatology]. Moscow: IMA-PRESS; 2018. 144 p.

4. Amirdzhanova VN, Kaigorodtseva EYu, Savenkova NA, Nasonov EL. Quality of life as a criterion of disease modifying antirheumaticdrug and biological agents therapy efficacy: results of international and Russian studies. Nauchno-prakticheskaya revma-tologiya = Rheumatology Science and Practice. 2009;47(2):54-66. (In Russ.). doi: 10.14412/1995-4484-2009-460

5. Amirdzhanova VN, Lukina GV, Nasonov EL. Quality of life of patients with rheumatoid arthritis receiving anti-B-cell therapy ( results of international studies and data of the Russian register). Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2009;47(1S):73-9. (In Russ.).

6. Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1.

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

8. Nasonov EL, Lila AM. Rheumatoid arthritis: achievements and unresolved problems. Terapevticheskii arkhiv. 2019;(5):4-7. (In Russ.).

9. Аletaha D, Smolen JS. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA. 2018 Oct 2;320(13):1360-1372. doi: 10.1001/jama.2018.13103.

10. 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. Epub 2015 May 12.

11. Van Vollenhoven R. Treat-to-target in rheumatoid arthritis — are we there yet? Nat Rev Rheumatol. 2019 Mar;15(3):180-186. doi: 10.1038/s41584-019-0170-5.

12. Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. Lancet. 2017 Jun 10;389(10086):2338-2348. doi: 10.1016/S0140-6736(17)31491-5.

13. Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv MusculoskeletDis. 2017 Oct;9(10):249-262. doi: 10.1177/1759720X17720366. Epub 2017 Aug 2.

14. Amirdzhanova VN, Koilubaeva GM. Quality of life assessment methodology in practice of rheumatologist. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2003;41(2):72-6. (In Russ.). doi: 10.14412/1995-4484-2003-773

15. Erdes Sh, Folomeeva OM, Amirdzhanova VN. Problems of rheumatic diseases in Russia from the standpoint of society and the patient. VestnikRAMN. 2003;(7):11-4. (In Russ.).

16. Amirdzhanova VN. Pain and HAQ scales in evaluation of patients with rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2006;44(2):60-5. (In Russ.).

17. Nasonov EL. Prospects for the development of rheumatology in the XXI century. Russkii meditsinskii zhurnal. 2001;(23):1031-2. (In Russ.).

18. Nasonov EL. Treatment of rheumatoid arthritis: the current state of the problem. Russkii meditsinskii zhurnal. 2006; (8):573-7. (In Russ.).

19. Nasonova VA. Rheumatology: a look into the XXI century. Vestnik RAMN. 2003;(7):3-6. (InRuss.).

20. Nasonov EL, editor. Genno-inzhenernye biologicheskie preparaty v lechenii revmatoidnogo artrita [Genetically engineered biological drugs in the treatment of rheumatoid arthritis]. Moscow: IMA-PRESS; 2013. 549 p.

21. Sigidin YaA, Lukina GV. Biologicheskaya terapiya v revmatologii [Biological therapy in rheumatology]. 2nd ed. Moscow: Prakticheskaya meditsina; 2009. 301 p.

22. Starkova AS, Amirdzhanova VN. Validation of the Russian language version of the RAPID-3 questionnaire. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2011;49(4):36-40. (In Russ.). doi: 10.14412/1995-4484-2011-59

23. Amirdzhanova VN, Koilubaeva GM, Goryachev DV, et al. Validation of the russian version of the HAQ. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2004;42(2):59-65. (In Russ.).

24. Amirdzhanova VN. Therapy efficacy assessment in patients with rheumatoid arthritis by quality of life measures. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2007;45(5):93-9. (In Russ.). doi: 10.14412/ 1995-4484-2007-28

25. Amirdzhanova VN. Rheumatoid arthritis from the standpoint of assessing the quality of life of patients. Terapevticheskii arkhiv. 2007;79(5):9-15. (In Russ.).

26. Amirdzhanova VN, Erdes Sh. Validation of general questionnaire EuroQol-5D (EQ-5D) Russian version. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2007;45(3):69-76. (In Russ.). doi: 10.14412/1995-4484-2007-691

27. Olyunin YuA. Assessment of disease activity in rheumatoid arthritis: recommendations and practice. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2014;8(2):15-20. (In Russ.). doi: 10.14412/1996-7012-2014-2-15-20

28. Gaujoux-Viala C, Mouterde G, Baillet A, et al. Evaluating disease activity in rheumatoid arthritis: which composite index is best? A systematic literature analysis of studies comparing the psychometric properties of the DAS, DAS28, SDAI and CDAI. Joint Bone Spine. 2012 Mar;79(2):149-55. doi: 10.1016/j.jbspin.2011.04.008. Epub 2011 Jun 15.

29. Ferreira RJO, Dougados M, Kirwan JR, et al. Drivers of patient global assessment in patients with rheumatoid arthritis who are close to remission: an analysis of 1588 patients. Rheumatology (Oxford). 2017 Sep 1; 56(9):1573-1578. doi: 10.1093/rheumatology/kex211.

30. Nikiphorou E, Radner H, Chatzidionysiou K, et al. Patient global assessment in measuring disease activity in rheumatoid arthritis: a review of the literature. Arthritis Res Ther. 2016 Oct 28;18(1):251.

31. Lisitsyna TA, Abramkin AA, Vel'tishchev DYu, et al. Chronic pain and depression in patients with rheumatoid arthritis: results of five-year follow-up. Terapevticheskii arkhiv. 2019;(5):8-18. (InRuss.).