The influence of tocilizumab immunogenicity markers on the effectiveness of treating rheumatoid arthritis

Vladimir D. Nazarov; Sergey V. Lapin; Ksenia V. Tulenko; Rusana R. Samigullina; Vadim I. Mazurov

doi:10.17816/mechnikov202012131-36

HERALD of North-Western State Medical University named after I.I. Mechnikov ›› 2020, Vol. 12 ›› Issue (1) : 31 -36. DOI: 10.17816/mechnikov202012131-36

Original study article

research-article

The influence of tocilizumab immunogenicity markers on the effectiveness of treating rheumatoid arthritis

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First Pavlov State Medical University of St. Petersburg

FSBEI HE North-Western State Medical University named after I. I. Mechnikov

Laboratory of autoimmune diseases, Scientific and Methodological Center for Molecular Medicine of the Ministry of Health Care of the Russian Federation

Head of the Laboratory of autoimmune diseases, Scientific and Methodological Center for Molecular Medicine of the Ministry of Health Care of the Russian Federation

PhD-student of Department of Therapy, Rheumatology, Examination of Temporary Disability and Quality of Medical Care named after E.E.Eichwald

assistant of Department of Therapy, Rheumatology, Examination of Temporary Disability and Quality of Medical Care named after E.E.Eichwald, MD

D. Sci. (Med.), Prof., RAS academician, Head of the research institute of Rheumatology North-Western State Medical University named after I.I. Mechnikov, head of Department of Therapy, Rheumatology, Examination of Temporary Disability and Quality of Medical Care named after E.E.Eichwald FSBEI HE North-Western State Medical University named after I. I. Mechnikov

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Abstract

Purpose. The study assesses the impact of tocilizumab immunogenicity markers on clinical response to conducted treatment in patients with rheumatoid arthritis.

Materials and methods. A total of 17 patients with the confirmed diagnosis of RA receiving tocilizumab therapy for more than 1 year were enrolled into the study. Blood serum samples were collected once every six months before every drug injection during 2.5 years of treatment. The concentration of antibodies to tocilizumab and level of tocilizumab was determined using the ELISA. Additionally, DAS28 values were measured at the first and the last patient visit during the course of study, whereas levels of C-reactive protein (CRP), white blood cells, platelets, rheumatoid factor, and circulating immune complexes were only measured at the last examination.

Results. Positive correlations between the antibodies to tocilizumab and the last point DAS28 values were found, as well as a negative correlation of tocilizumab level and the level of DAS28.

Conclusions. The data obtained indicate a significant effect of serum levels of tocilizumab, as well as of the concentration of antibodies to tocilizumab on the effectiveness of RA treatment. A routine study of these biomarkers might be useful for individualizing treatment approaches for RA patients and determining the causes of tocilizumab resistance.

Keywords

tocilizumab / immunogenicity / rheumatoid arthritis

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Vladimir D. Nazarov, Sergey V. Lapin, Ksenia V. Tulenko, Rusana R. Samigullina, Vadim I. Mazurov. The influence of tocilizumab immunogenicity markers on the effectiveness of treating rheumatoid arthritis. HERALD of North-Western State Medical University named after I.I. Mechnikov, 2020, 12(1): 31-36 DOI:10.17816/mechnikov202012131-36

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References

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[1]	Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023-2038. https://doi.org/ 10.1016/S0140-6736(16)30173-8.

[2]	Hazlewood GS, Rezaie A, Borman M, et al. Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn’s disease: a network meta-analysis. Gastroenterology. 2015;148(2):344-354.e5. https://doi.org/10.1053/j.gastro. 2014.10.011.

[3]	Ding NS, Hart A, De Cruz P. Systematic review: predicting and optimising response to anti-TNF therapy in Crohn’s disease – algorithm for practical management. Aliment Pharmacol Ther. 2016;43(1):30-51. https://doi.org/10.1111/apt.13445.

[4]	Kaliyaperumal A, Jing S. Immunogenicity assessment of therapeutic proteins and peptides. Curr Pharm Biotechnol. 2009;10(4):352-358. https://doi.org/10.2174/ 138920109788488860.

[5]	Kalden JR, Schulze-Koops H. Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment. Nat Rev Rheumatol. 2017;13(12):707-718. https://doi.org/10.1038/nrrheum.2017.187.

[6]	Deisenhammer F. Interferon-beta: neutralizing antibodies, binding antibodies, pharmacokinetics and pharmacodynamics, and clinical outcomes. J Interferon Cytokine Res. 2014;34(12):938-945. https://doi.org/10.1089/jir.2012.0135.

[7]	Biggioggero M, Crotti C, Becciolini A, Favalli EG. Tocilizumab in the treatment of rheumatoid arthritis: an evidence-based review and patient selection. Drug Des Devel Ther. 2019;13:57-70. https://doi.org/10.2147/DDDT.S150580.

[8]	Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. https://doi.org/10.1002/art.27584.

[9]	Burmester GR, Choy E, Kivitz A, et al. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76(6):1078-1085. https://doi.org/10.1136/annrheumdis-2016-210297.