Evaluation of rituximab therapy in real clinical practice (according to the OREL registry of patients with rheumatoid arthritis

Objective: to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).

Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.

Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p<0.05).

Conclusion. The analysis of RTM therapy in RA patients in real clinical practice demonstrated that in most cases RTM was given as the first BA, in combination with DMARDs, the main agent of which was methotrexate. The use of RTM was accompanied by a significant reduction in disease activity and in the serum levels of acute-phase reactants and autoantibodies.

1. Насонов ЕЛ. Ритуксимаб. В кн.: Насонов ЕЛ, редактор. Генно-инженерные биологические препараты в лечении ревматоидного артрита. Москва: ИМА-ПРЕСС; 2013. С. 200-21 [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 (In Russ.)].

2. Smolen JS, Aletaha D, McInnes I. Rheumatoid arthritis. Lancet. 2016;388:2023-38. doi: 10.1016/S0140-6736(16)30173-8

3. 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

4. Насонов ЕЛ, редактор. Ревматология. Российские клинические рекомендации. Москва: ГЭОТАР-Медиа; 2017. 456 с. [Nasonov EL, editor. Revmatologiya. Rossiiskie klinicheskie rekomendatsii [Rheumatology. Russian clinical guidelines]. Moscow: GEOTAR-media; 2017. 456 p. (In Russ.)].

5. Emery P, Fleishmann R, Filipowicz-Sosnowska A, et al; for the DANCER Study group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment. Results of a phase IIb randomized, double-blind, placebo-controlled dose-range trial. Arthritis Rheum. 2006;54:1390-400. doi: 10.1002/art.21778

6. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Results of multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793-806. doi: 10.1002/art.22025

7. Emery P, Deodhar A, Rigby WF, et al. Efficacy and safety of different doses and retreatment of Rituximab: a randomized, placebo- controlled trial in patients who are biologically naive with active rheumatoid arthritis and anadequate response to methotrexate (Study Evaluating Rituximab`s Efficacy in MTX inadequate responders (SERENA). Ann Rheum Dis. 2010;69:1629-35. doi: 10.1136/ard.2009.119933

8. Rubbert-Roth A, Tak PP, Zebrini C, et al. Efficacy and safety of various repeat treatment dosing regimes in Rituximab in patients with active rheumatoid arthritis: results of a phase III randomized study (MIRROR) dosing regimens of rituximab in patients with active RA: results of a phase III randomized study (MIRROR). Rheumatology. 2010;49:1683-93. doi: 10.1093/rheumatology/keq116

9. Насонов ЕЛ, Лукина ГВ, Сигидин ЯА и др. Применение моноклональных антител в В-лимфоцитам (ритуксимаб) при ревматоидном артрите в России (Предварительные результаты Российского регистра). Терапевтический архив. 2008;80(8):57-62 [Nasonov EL, Lukina GV, Sigidin YaA, et al. The use of monoclonal antibodies in B-lymphocytes (rituximab) in rheumatoid arthritis in Russia (Preliminary results of the Russian Registry). Terapevticheskii Arkhiv. 2008;80(8):57-62 (In Russ.)].

10. Gottenberg JE, Ravaud P, Bardin T, et al. Risk factors of severe infections in patients with rheumatoid arthritis treated with Rituximab in the Autoimmunity and Rituximab (AIR) registry. Arthritis Rheum. 2010;62:2625-32. doi: 10.1002/art.27555

11. Torrente-Segarra V, Acosta Pereira A, Morla R, et al. VARIAR Study: Assessment of Short-term Efficacy and Safety of Rituximab Compared to an Tumor Necrosis Factor Alpha Antagonists as Second-line Drug Therapy in Patients With Rheumatoid Arthritis Refractory to a First Tumor Necrosis Factor Alpha Antagonist. Reumatol Clin. 2016;12(6):319-22. doi: 10.1016/j.reumae.2015.11.020

12. Keyser FD, Hoffman I, Durez P, et al. Longterm Followup of Rituximab Therapy in Patients with Rheumatoid Arthritis: Results from the Belgian MabThera in Rheumatoid Arthritis Registry. J Rheumatol. 2014;41:1761-5. doi: 10.3899/jrheum.131279

13. Harrold LR, Reed GW, Shewade A, et al. Effectiveness of rituximab for the treatment of rheumatoid arthritis in patients with prior exposure to anti-TNF: results from the CORRONA registry. J Rheumatol. 2015;42:1090-8. doi: 10.3899/jrheum.141043

14. Wendler J, Burmester GR, Sö rensen H, et al. Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): six-year results from a prospective, multicentre, non-interventional study in 2,484 patients. Arthritis Res Ther. 2014;16:80. doi: 10.1186/ar4521

15. Chatzidionysiou K, Lie E, Nasonov E, et al. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration Arthritis Res Ther. 2016;18:50. doi: 10.1186/s13075-016-0951-z

16. Keystone E, Fleishmann R, Emery P, et al. Sustained efficacy is achieved with repeat courses of rituxumab in patients with rheumatoid arthritis with inadequate response to one or more TNF inhibitors. Rheumatology. 2010;49(1):98(173).

17. Cohen S, Keystone E, Genovese M, et al. Continued inhibition of structural damage in rheumatoid arthritis patients treated with Rituximab at 2 years: REFLEX study. Ann Rheum Dis. 2010;69:1158-61. doi: 10.1136/ard.2009.119222

18. Chatzidionysiou K, Lie E, Nasonov E, et al. Highest clinical effectiveness of Rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed: pooled data from 10 European registries. Ann Rheum Dis. 2011;70:1575-80. doi: 10.1136/ard.2010.148759

19. Насонов ЕЛ. Биоаналоги в ревматологии. Научно-практиче- ская ревматология. 2016;54(6):628-40 [Nasonov EL. Biosimilars in rheumatology. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(6):628-40 (In Russ.)]. doi: 10.14412/1995-4484-2016-628-640

20. Насонов ЕЛ, Зонова ЕВ, Иванова ОН и др. Результаты сравни- тельного клинического исследования III фазы препаратов ритуксимаб (Ацеллбия и Мабтера) при ревматоидном артрите (исследование BIORA). Научно-практическая ревматология. 2016;54(5):510-9 [Nasonov EL, Zonova EV, Ivanova ON, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia® and MabThera®) in rheumatoid arthritis (the BIORA study). Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(5):510-9 (In Russ.)]. doi: 10.14412/1995-4484-2016-510-519

21. Насонов ЕЛ, Каратеев ДЕ, Сатыбалдыев АМ и др. Ревматоидный артрит в Российской Федерации по данным Российского регистра больных артритом (сообщение I). Научно-практическая ревматология. 2015;53(5):472-84 [Nasonov EL, Karateev DE, Satybaldyev AM, et al. Rheumatoid arthritis in the Russian Federation according to Russian Arthritis Registry data (Communication 1). Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(5):472-84 (In Russ.)]. doi: 10.14412/1995-4484-2015-472-484

22. Cuppen BV, Welsing PM, Sprengers JJ, et al. Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability. Rheumatology (Oxford). 2016;55(5):826-39. doi: 10.1093/rheumatology/kev

23. Александрова ЕН, Авдеева АС, Лукина ГВ и др. Клинико-иммунологические эффекты анти-В-клеточной терапии у больных ревматоидным артритом. Научно-практическая ревматология. 2012;50(1):14-21 [Aleksandrova EN, Avdeyeva AS, Lukina GV, et al. The clinical and immunological effects of anti-B-cell therapy in patients with rheumatoid arthritis. Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2012;50(1):14-21 (In Russ.)]. doi: 10.14412/1995-4484-2012-498

24. Tak P, Rigby W, Rubbert-Roth A. Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial. Ann Rheum Dis. 2011;70:39-46. doi: 10.1136/ard.2010.137703

25. Bae SC, Lee YH. Comparative efficacy and safety of biosimilar rituximab and originator rituximab in combination with methotrexate in patients with active rheumatoid arthritis: A Bayesian network meta-analysis. Int J Clin Pharmacol Ther. 2019;57(4):188-96. doi: 10.5414/CP203360

26. Tony HP, Krü ger K, Cohen SB, et al. Brief Report: Safety and Immunogenicity of Rituximab Biosimilar GP 2013 After Switch From Reference Rituximab in Patients With Active Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2019;71(1):88-94. doi: 10.1002/acr.23771