Safety and efficacy of rituximab in the treatment of paediatric autoimmune diseases
Authors:
V. Lukášová 1; H. Schneiderová 2; V. Fiamoli 1; O. Zapletal 1; S. Köhlerová 1; J. Blatný 1
Authors‘ workplace:
Oddělení dětské hematologie FN Brno a Masarykova univerzita Brno
1; Pediatrická klinika FN Brno a Masarykova univerzita Brno
2
Published in:
Transfuze Hematol. dnes,24, 2018, No. 4, p. 270-282.
Category:
Original Papers
Overview
Rituximab is a monoclonal antibody directed against CD20 molecules expressed on the surface of B lymphocytes. After binding to the cell surface, rituximab induces B cell death and this leads to transient depletion of B cells associated with a reduction/disappearance of pathological (auto) antibodies. This effect is used in the treatment of autoimmune diseases (off-label mode).
Aim of this work is to assess the safety and efficacy of rituximab in a group of 11 paediatric patients with autoimmune diseases. Data were collected retrospectively, thus the results of certain parameters were not available for all enrolled patients. From a safety point of view, attention was focused on both acute drug-related side effects and long-term adverse effects, including long-term B cell depletion, hypogammaglobulinemia and serious infections. Effectivity of the treatment was assessed as achievement of partial and/or complete remission criteria for respective diagnoses.
In the study population, acute adverse reactions were reported in 5 patients (45.5% of all patients). In 2 patients (25% of patients with data available), even after substantial follow-up, B cell recovery did not return to physiological values. Moderate hypogammaglobulinemia after therapy was seen in 2 patients (25% of patients with data available). Serious infections after therapy were reported in 1 patient (9.1% of all patients). We considered rituximab to be effective in 45.5% of our patients. Complete remission was achieved in 9% of patients, partial remission in 36.5% of patients. Long-term remission lasting more than 1 year was reached and maintained in 27.3% of the monitored patients.
Our results correspond to current recommendations, that rituximab should be considered as second-line treatment in patients with autoimmune disease in children.
Key words:
rituximab – autoimmune diseases in children – adverse events – hypogammaglobulinemia – remission
Sources
1. Pescovitz MD. Rituximab, an Anti-CD20 monoclonal antibody: history and mechanism of action. Am J Transplant 2006;5p1(6):859–866.
2. Randall KL. Rituximab in autoimmune diseases. Austr Prescriber 2016;4(39):131–134.
3. El-Hallak M, Binstadt BA, Leichtner AM, et al. Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. J Ped 2007;4(150):376–382.
4. Cooper N, Arnold DM. The effect of rituximab on humoral and cell mediated immunity and infection in the treatment of autoimmune diseases. Br J Haematol 2010;1(149):3–13.
5. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene 2003;22(47):7359–7368.
6. Harb D. The off-label use of rituximab for the management of inflammatory disorders: American University of Beirut Medical Center experience. Arch Rheumatol 2014;29(3):194–202.
7. Butterly SJ, Pillans P, Horn B, Miles R, Sturtevant J. Off-label use of rituximab in a tertiary Queensland hospital. Int Med J 2010;40(6):443–452.
8. Etemadifar M, Salari M, Mirmosayyeb O, et al. Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence. J Res Med Sci 2016;21(11):1–7.
9. Kumar D, Roubey RA. Use of rituximab in the antiphospholipid syndrome. Cur Rheumatol Rep 2010;12(1):40–44.
10. Nieto-Rios JF, De Los Ríos SMG, Serna-Higuita LM, et al. Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor. Colombia Med 2016;47(4):196–202.
11. Van Vollenhoven RF, Emery P, Bingham CO, et al. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. Roman J Rheumatol 2010;19(1):20–30.
12. Levin AS, Otani IM, Lax T, Hochberg E, Banerji A. Reactions to rituximab in an outpatient infusion center. J Allergy Clin Immunol In Pract 2017;5(1):107–113.
13. Froissart A, Veyradier A, Hié M, Benhamou Y, Coppo P. Rituximab in autoimmune thrombotic thrombocytopenic purpura. Eur J Int Med 2015;26(9):659–665.
14. Roberts DM, Jones RB, Smith RM, et al. Rituximab-associated hypogammaglobulinemia: Incidence, predictors and outcomes in patients with multi-system autoimmune disease. J Autoimmun 2015;57:60–65.
15. Brown BA, Torabi M. Incidence of infusion-associatedr with rituximab for treating multiple sclerosis. Drug Safety 2011;34(2):117–123.
16. Pritchard CH, Greenwald MW, Kremer JM, et al. Safety of infusing rituximab at a more rapid rate in patients with rheumatoid arthritis: results from the RATE-RA study. BMC Musculoskeletal Disorders 2014;15(1):1–18.
17. Šimkovič M, Vodárek P, Motyčková M, Žák P, Smolej L. Infuzní toxicita rituximabu u nemocných s chronickou lymfocytární leukemií. Vnitř Lék 2015;61(7–8):626–632.
18. Kemeng W, Guoqing W, Delong L. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol 2012;1(1):36.
19. SPC (Mabthera, Roche). Dostupné na www: http://www.ema.europa.eu/docs/cs_CZ/document_library/EPAR_-_Product_Information/human/000165/WC500025821.pdf.
20. Lawrence DP, Garratty G. Immune hemolytic anemias. 2. vyd. Philadelphia, Churchill Livingstone, 2004; p. 69–70.
21. Robertson JD, Higgins P, Price J, Dunkley S, Barrese G, Curtin J. Immune tolerance induction using a factor VIII/von Willebrand factor concentrate, with or without immunosuppression, in Australian paediatric severe haemophilia A patients with high titre inhibitors: A multicentre, retrospective study. Thromb Res 2014;134(5):1046–1051.
22. Collins PW, Mathias M, Hanley M, et al. Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort. J Thromb Haemost 2009;7(5):787–794.
23. Franchini M, Mengoli C, Lippi G, et al. Immune tolerance with rituximab in congenital haemophilia with inhibitors: a systematic literature review based on individual patients’ analysis. Haemophilia 2008;14(5):903–912.
24. Carcao M, St Louis J, Poon MC, et al. Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience. Haemophilia 2006;12(1):7–18.
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Haematology Internal medicine Clinical oncologyArticle was published in
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2018 Issue 4
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