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Evaluation of effectiveness of long-term therapy with Russian rituximab biosimilar in Sjogren’s disease in real clinical practice

https://doi.org/10.47360/1995-4484-2025-286-297

Abstract

The aim – to evaluate the effectiveness of long-term therapy with Russian rituximab (RTX) biosimilar in Sjögren’s disease (SjD) in real-life clinical practice.

Materials and methods. The retrospective study included 53 patients with SjD (Russian 2001 criteria and ACR/ EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) 2016 criteria), observed at the V.A. Nasonova Research Institute of Rheumatology from 2017 to 2024 and receiving long-term RTX therapy (Russian biosimilar Acellbia®, BIOCAD). The signs of clinical and laboratory activity of the disease, stomatological and ophthalmological tests, as well as the incidence of new systemic manifestations and lymphomas were assessed dynamically.

Results. The median duration of RTX therapy was 27 [19; 55] months, and the median total dose was 4 [3.5; 5.5] g. Before the therapy, 13 (25%) patients had recurrent parotitis, which was relieved in all patients during the therapy. Persistent enlargement of the salivary glands was observed in 10 (20.4%) patients, in 9 of them it was relieved. A significant increase in stimulated saliva flow was found (from 1.5 [0.5; 3] to 2.4 [1.4; 3.5] ml; p=0.002), an increase in salivation was found in 51% of patients, stabilization in 28.6%, and deterioration in 20.4%. When assessing the ultrasound dynamics of the salivary glands, the size of hypoechoic avascular lesions significantly decreased (from 1.8 [1.3; 2.3] to 1.3 [1.1; 1.5] mm; p<0.001), and according to the ultrasound activity index, stabilization was noted in 67.4% of patients, improvement in 27.9%, and deterioration in 4.7% of patients. When assessing the dynamics of sialography, the size of cavities significantly decreased (from 1.5 [1.5; 2.5] to 1.0 [0; 1.5] mm; p<0.001), and according to the assessment of sialographic stages, stabilization was noted in 67.5% of patients, improvement in 32.5% of patients, and deterioration was not noted in any patient. When assessing the lacrimal glands function, a significant increase in lacrimation was found according to the stimulated Schirmer’s test (from 6 [3.75; 12] to 8 [5; 15] mm; p=0.005); an increase in lacrimation was noted in 38% of patients, stabilization in 40.6%, and a decrease in 21.4%. When assessing the tear break-up time, a tendency towards its increase was noted, but statistically insignificant (from 5 [3.75; 9.25] to 5.5 [4; 9] sec; p=0.35). Corneal epitheliopathy during the therapy was relieved in 44% and persisted in 56% of patients; worsening of corneal epitheliopathy during the treatment was observed in a few patients, while no cases of ulcer formation or perforation of the cornea were recorded. During the therapy, a significant decrease in the levels of erythrocyte sedimentation rate, gamma globulins, IgG, IgA, IgM, rheumatoid factor, an increase in the C3 complement level, and the elimination of monoclonal gammopathy were observed, while the dynamics of the C4 complement level and cryoglobulinemia were multidirectional. The median duration of B lymphocyte depletion was 5 [4; 6] months, constant depletion could be maintained only in 59.6% of patients. During the therapy, the SjD systemic activity index (ESSDAI, EULAR Sjögren’s Syndrome Disease Activity Index) significantly decreased (from 5 [2; 8] to 1 [0; 3] points; p<0.001), and minimal clinically important improvement of this index was achieved in 66.6% of patients. During the observation, one patient developed a new skin lesion (lupus chilblain); no other new systemic manifestations or lymphomas were registered.

Conclusion. According to our retrospective study conducted in real-life clinical practice, long-term therapy with Russian RTX biosimilar in most cases (60–80%) led to stabilization or improvement of SjD manifestations. RTX can be used to treat not only systemic but also glandular manifestations of the disease. Given the lack of an optimal response to RTX therapy in a number of SjD patients, it is necessary to study the effectiveness of drugs that lead to a deeper depletion of B lymphocytes.

About the Authors

B. D. Chaltsev
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Bogdan D. Chaltsev.

115522, Moscow, Kashirskoye Highway 34A


Competing Interests:

None



V. I. Vasilyev
Revmotsentr LLC
Russian Federation

Vladimir I. Vasilyev.

107140, Moscow, Nizhnyaya Krasnoselskaya str., 4


Competing Interests:

None



A. V. Torgashina
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Anna V. Torgashina.

115522, Moscow, Kashirskoye Highway 34A


Competing Interests:

None



Yu. I. Khvan
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Yulia I. Khvan.

115522, Moscow, Kashirskoye Highway 34A


Competing Interests:

None



E. B. Rodionova
Treatment Center LLC
Russian Federation

Ekaterina B. Rodionova.

119021, Moscow, T. Frunze str., 15/1


Competing Interests:

None



E. I. Selifanova
I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)
Russian Federation

Elena I. Selifanova.

119991, Moscow, Trubetskaya str., 8, building 2


Competing Interests:

None



T. N. Safonova
Revmotsentr LLC
Russian Federation

Tatiana N. Safonova.

107140, Moscow, Nizhnyaya Krasnoselskaya str., 4


Competing Interests:

None



L. A. Semenova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Lyudmila A. Semenova.

115522, Moscow, Kashirskoye Highway 34A


Competing Interests:

None



M. V. Burtseva
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Marina V. Burtseva.

115522, Moscow, Kashirskoye Highway 34A


Competing Interests:

None



S. I. Glukhova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation

Svetlana I. Glukhova.

115522, Moscow, Kashirskoye Highway 34A


Competing Interests:

None



References

1. Tzioufas AG, Voulgarelis M. Update on Sjögren’s syndrome autoimmune epithelitis: From classification to increased neoplasias. Best Pract Res Clin Rheumatol. 2007;21(6):989-1010. doi: 10.1016/j.berh.2007.09.001

2. van Ginkel MS, Haacke EA, Bootsma H, Arends S, van Nimwegen JF, Verstappen GM, et al. Presence of intraepithelial B-lymphocytes is associated with the formation of lymphoepithelial lesions in salivary glands of primary Sjögren’s syndrome patients. Clin Exp Rheumatol. 2019;37 Suppl 118(3):42-48.

3. Safonova TN, Vasiliev VI, Likhvantseva VG. Sjogren’s syndrome: A guide for physicians. Moscow:Moscow State University Publishing House;2013 (In Russ.).

4. Chatzis LG, Stergiou IE, Goules AV, Pezoulas V, Tsourouflis G, Fotiadis D, et al. Clinical picture, outcome and predictive factors of lymphoma in primary Sjögren’s syndrome: Results from a harmonized dataset (1981–2021). Rheumatology (Oxford). 2022;61(9):3576-3585. doi: 10.1093/rheumatology/keab939

5. Hernández-Molina G, Kostov B, Brito-Zerón P, Vissink A, Mandl T, Hinrichs AC, et al.; Sjögren Big Data Consortium. Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies. Rheumatology (Oxford). 2022;62(1):243-255. doi: 10.1093/rheumatology/keac205

6. Pringle S, Verstappen GM, van Ginkel MS, Nakshbandi U, Girigoria Z, Bootsma H, et al. Lymphoepithelial lesions in the salivary glands of primary Sjögren’s syndrome patients: The perfect storm? Clin Exp Rheumatol. 2022;40(12):2434-2442. doi: 10.55563/clinexprheumatol/06an99

7. Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, et al. Reduction of fatigue in Sjögren syndrome with rituximab: Results of a randomised, double-blind, placebo-controlled pilot study. Ann Rheum Dis. 2008;67(11):1541-1544. doi: 10.1136/ard.2007.083865

8. Meijer JM, Meiners PM, Vissink A, Spijkervet FK, Abdulahad W, Kamminga N, et al. Effectiveness of rituximab treatment in primary Sjögren’s syndrome: A randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010;62(4):960-968. doi: 10.1002/art.27314

9. Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puéchal X, et al. Treatment of primary Sjögren syndrome with rituximab: A randomized trial. Ann Intern Med. 2014;160(4):233-242. doi: 10.7326/M13-1085

10. Bowman SJ, Everett CC, O’Dwyer JL, Emery P, Pitzalis C, Ng WF, et al. Randomized controlled trial of rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjögren’s syndrome. Arthritis Rheumatol. 2017;69(7):1440-1450. doi: 10.1002/art.40093

11. Arends S, Verstappen GM, de Wolff L, Pringle S, Kroese FGM, Vissink A, et al. Why do drug treatments fail in Sjögren’s disease? Considerations for treatment, trial design and interpretation of clinical efficacy. Expert Rev Clin Immunol. 2023;19(10):1187-1194. doi: 10.1080/1744666X.2023.2234641

12. Ramos-Casals M, Brito-Zerón P, Bombardieri S, Bootsma H, De Vita S, Dörner T, et al.; EULAR-Sjögren Syndrome Task Force Group. EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies. Ann Rheum Dis. 2020;79(1):3-18. doi: 10.1136/annrheum-dis-2019-216114

13. Price EJ, Benjamin S, Bombardieri M, Bowman S, Carty S, Ciurtin C, et al. British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease. Rheumatology (Oxford). 2025;64(2):409-439. doi: 10.1093/rheumatology/keae152

14. Flores-Chávez A, Kostov B, Solans R, Fraile G, Maure B, Feijoo-Massó C, et al.; GEAS-SS SEMI Registry. Severe, life-threatening phenotype of primary Sjögren’s syndrome: Clinical characterisation and outcomes in 1580 patients (GEAS-SS Registry). Clin Exp Rheumatol. 2018;36 Suppl 112(3):121-129.

15. Nasonov EL, Zonova EV, Ivanova ON, Knyazeva LA, Mazurov VI, Samigullina RR, et al. The results of a phase III comparative clinical trial of rituximab (Acellbia® and Mabthera®) in rheumatoid arthritis (the BIORA study). Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2016;54(5):510-519 (In Russ.). doi: 10.14412/1995-4484-2016-510-519

16. Shiboski CH, Shiboski SC, Seror R, Criswell LA, Labetoulle M, Lietman TM, et al.; International Sjögren’s Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism Classification criteria for primary Sjögren’s syndrome: A consensus and data-driven methodology involving three international patient cohorts. Arthritis Rheumatol. 2017;69(1):35-45. doi: 10.1002/art.39859

17. Seror R, Bowman SJ, Brito-Zeron P, Theander E, Bootsma H, Tzioufas A, et al. EULAR Sjögren’s syndrome disease activity index (ESSDAI): A user guide. RMD Open. 2015;1(1):e000022. doi: 10.1136/rmdopen-2014-000022

18. Alvariño C, Bagan L, Murillo-Cortes J, Calvo J, Bagan J. Stimulated whole salivary flow rate: The most appropriate technique for assessing salivary flow in Sjögren syndrome. Med Oral Patol Oral Cir Bucal. 2021;26(3):e404-e407. doi: 10.4317/medoral.24736

19. Blatt IM, French AJ, Holt JF, Maxwell JH, Rubin P. Secretory sialography in diseases of the major salivary glands. Ann Otol Rhinol Laryngol. 1956;65(2):295-317. doi: 10.1177/000348945606500201

20. Jousse-Joulin S, D’Agostino MA, Nicolas C, Naredo E, Ohrndorf S, Backhaus M, et al. Video clip assessment of a salivary gland ultrasound scoring system in Sjögren’s syndrome using consensual definitions: An OMERACT ultrasound working group reliability exercise. Ann Rheum Dis. 2019;78(7):967-973. doi: 10.1136/annrheumdis-2019-215024

21. Fisher BA, Jonsson R, Daniels T, Bombardieri M, Brown RM, Morgan P, et al.; Sjögren’s histopathology workshop group (appendix) from ESSENTIAL (EULAR Sjögren’s syndrome study group). Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren’s syndrome. Ann Rheum Dis. 2017;76(7):1161-1168. doi: 10.1136/annrheumdis-2016-210448

22. Whitcher JP, Shiboski CH, Shiboski SC, Heidenreich AM, Kitagawa K, Zhang S, et al.; Sjögren’s International Collaborative Clinical Alliance Research Groups. A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögren’s Syndrome International Registry. Am J Ophthalmol. 2010;149(3):405-415. doi: 10.1016/j.ajo.2009.09.013

23. Verstappen GM, Ice JA, Bootsma H, Pringle S, Haacke EA, de Lange K, et al. Gene expression profiling of epithelium-associated FcRL4+ B cells in primary Sjögren’s syndrome reveals a pathogenic signature. J Autoimmun. 2020;109:102439. doi: 10.1016/j.jaut.2020.102439

24. Chatzis L, Goules AV, Pezoulas V, Baldini C, Gandolfo S, Skopouli FN, et al. A biomarker for lymphoma development in Sjogren’s syndrome: Salivary gland focus score. J Autoimmun. 2021;121:102648. doi: 10.1016/j.jaut.2021.102648

25. Arends S, de Wolff L, van Nimwegen JF, Verstappen GMPJ, Vehof J, Bombardieri M, et al. Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS): Development and validation of a novel outcome measure. Lancet Rheumatol. 2021;3(8):e553-e562. doi: 10.1016/S2665-9913(21)00122-3

26. Seror R, Baron G, Camus M, Cornec D, Perrodeau E, Bowman SJ, et al.; NECESSITY WP5-STAR development working group. Development and preliminary validation of the Sjögren’s Tool for Assessing Response (STAR): A consensual composite score for assessing treatment effect in primary Sjögren’s syndrome. Ann Rheum Dis. 2022;81(7):979-989. doi: 10.1136/annrheumdis-2021-222054

27. Fisher BA, Everett CC, Rout J, O’Dwyer JL, Emery P, Pitzalis C, et al. Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: Results of the TRACTISS randomised double-blind multicentre substudy. Ann Rheum Dis. 2018;77(3):412-416. doi: 10.1136/annrheumdis-2017-212268

28. Pers JO, Devauchelle V, Daridon C, Bendaoud B, Le Berre R, Bordron A, et al. BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren’s syndrome. Arthritis Rheum. 2007;56(5):1464-1477. doi: 10.1002/art.22603

29. Cornec D, Costa S, Devauchelle-Pensec V, Jousse-Joulin S, Marcorelles P, Berthelot JM, et al. Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjögren’s syndrome. J Autoimmun. 2016;67:102-110. doi: 10.1016/j.jaut.2015.11.002

30. Delli K, Haacke EA, Kroese FG, Pollard RP, Ihrler S, van der Vegt B, et al. Towards personalised treatment in primary Sjögren’s syndrome: Baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis. 2016;75(11):1933-1938. doi: 10.1136/annrheumdis-2015-208304

31. Haacke EA, Bootsma H, Spijkervet FKL, Visser A, Vissink A, Kluin PM, et al. FcRL4+ B-cells in salivary glands of primary Sjögren’s syndrome patients. J Autoimmun. 2017;81:90-98. doi: 10.1016/j.jaut.2017.03.012

32. Pontarini E, Sciacca E, Chowdhury F, Grigoriadou S, Rivellese F, Murray-Brown WJ, et al.; Trial for Anti-B Cell Therapy in Patients with Primary Sjögren Syndrome Study Research Group. Serum and tissue biomarkers associated with Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) and Sjögren Tool for Assessing Response (STAR) to B cell-targeted therapy in the Trial of Anti-B Cell Therapy in Patients with Primary Sjögren Syndrome (TRACTISS). Arthritis Rheumatol. 2024;76(5):763-776. doi: 10.1002/art.42772

33. De Vita S, Isola M, Baldini C, Goules AV, Chatzis LG, Quartuccio L, et al. Predicting lymphoma in Sjögren’s syndrome and the pathogenetic role of parotid microenvironment through precise parotid swelling recording. Rheumatology (Oxford). 2023;62(4):1586-1593. doi: 10.1093/rheumatology/keac470

34. Vital EM, Wittmann M, Edward S, Md Yusof MY, MacIver H, Pease CT, et al. Brief report: Responses to rituximab suggest B cell-independent inflammation in cutaneous systemic lupus erythematosus. Arthritis Rheumatol. 2015;67(6):1586-1591. doi: 10.1002/art.39085

35. Shi H, Gudjonsson JE, Kahlenberg JM. Treatment of cutaneous lupus erythematosus: Current approaches and future strategies. Curr Opin Rheumatol. 2020;32(3):208-214. doi: 10.1097/BOR.0000000000000704

36. Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010;62(1):222-233. doi: 10.1002/art.27233

37. Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, et al.; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: The Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215-1226. doi: 10.1002/art.34359

38. Carsons SE, Vivino FB, Parke A, Carteron N, Sankar V, Brasington R, et al. Treatment guidelines for rheumatologic manifestations of Sjögren’s syndrome: Use of biologic agents, management of fatigue, and inflammatory musculoskeletal pain. Arthritis Care Res (Hoboken). 2017;69(4):517-527. doi: 10.1002/acr.22968

39. Pezot M, Nocturne G, Belkhir R, Henry J, Pavy S, Seror R, et al. Obinutuzumab in patients with Sjogren’s disease immunised against rituximab. Ann Rheum Dis. 2024;83(3):407-408. doi: 10.1136/ard-2023-224999

40. Mariette X, Barone F, Baldini C, Bootsma H, Clark KL, De Vita S, et al. A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren’s syndrome. JCI Insight. 2022;7(23):e163030. doi: 10.1172/jci.insight.163030

41. Bowman SJ, Fox R, Dörner T, Mariette X, Papas A, Grader-Beck T, et al. Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren’s syndrome: A randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet. 2022;399(10320):161-171. doi: 10.1016/S0140-6736(21)02251-0

42. Ramwadhdoebe TH, van Baarsen LGM, Boumans MJH, Bruijnen STG, Safy M, Berger FH, et al. Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis. Rheumatology (Oxford). 2019;58(6):1075-1085. doi: 10.1093/rheumatology/key428

43. Nasonov EL, Rumyantsev AG, Samsonov MYu. Pharmacotherapy of autoimmune rheumatic diseases – from monoclonal antibodies to CAR T cells: 20 years later. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2024;62(3):262-279 (In Russ.). doi: 10.47360/1995-4484-2024-262-279


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For citations:


Chaltsev B.D., Vasilyev V.I., Torgashina A.V., Khvan Yu.I., Rodionova E.B., Selifanova E.I., Safonova T.N., Semenova L.A., Burtseva M.V., Glukhova S.I. Evaluation of effectiveness of long-term therapy with Russian rituximab biosimilar in Sjogren’s disease in real clinical practice. Rheumatology Science and Practice. 2025;63(3):286-297. (In Russ.) https://doi.org/10.47360/1995-4484-2025-286-297

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ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)