Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with high morbidity if untreated. Sometimes, despite aggressive treatments, the disease remains active with cumulative organic damage. We conducted a retrospective and descriptive observational study of patients with SLE refractory to conventional treatment who were treated with rituximab (RTX) as remission induction therapy and maintenance. There was a significant reduction in the conventional immunosuppressive drug dose and the number of relapses of disease. RTX appeared to be effective and safe for the induction and maintenance of remission in patient with SLE refractory to conventional treatment. 1. Introduction Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with no permanent cure or high morbidity if left untreated [1]. Sometimes, despite aggressive treatments with high dose of glucocorticoids and immunosuppressive drugs, the disease remains active with cumulative organic damage [2]. The disease severity appears to be higher in Hispanics compared to Caucasians. Thus, the overall survival rates vary by race and ethnic background with a 5-year survival rate of approximately 95% among whites, 90% among blacks, and 87% among Hispanics [3]. The management of patients with SLE depends on the type of organ involvement and severity of the disease. When manifestations are severe, with threatening life conditions, the treatment is based on high-dose steroids, plasmapheresis, intravenous gamma globulin, and various types of immunosuppressants such as cyclophosphamide, azathioprine, or mofetil mycophenolate [4]. Some patients remain with active disease despite full immunosuppressive drugs. Two monoclonal antibodies targeting B cells have been used successfully in refractory SLE: belimumab directed against B-cell activating factor (BAFF) [5] and Rituximab which is a genetically engineered chimeric anti-CD20 monoclonal antibody. CD20 is a B-cell surface antigen that is expressed only on pre-B and mature B cells. It is not present on stem cells and is lost before differentiation of B cells into plasma cells. Therefore, rituximab causes a selective transient depletion of the CD20+ B-cell subpopulation [6]. Rituximab (RTX) is currently approved for the management of B-cell lymphomas, rheumatoid arthritis (RA) and systemic vasculitis ANCA (antineutrophil cytoplasmic antibodies) positive [7, 8], and it is used as a single dose for SLE crisis with varying results [9–11]. There are few reports in the literature about routine and chronic use of RTX as a
References
[1]
R. Cervera, M. A. Khamashta, J. Font et al., “Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1.000 patients,” Medicine, vol. 82, no. 5, pp. 299–308, 2003.
[2]
G. C. Tsokos, “Mechanisms of disease: systemic lupus erythematosus,” The New England Journal of Medicine, vol. 365, no. 22, pp. 2110–2121, 2011.
[3]
G. J. Pons-Estel, G. S. Alarcón, L. Scofield, L. Reinlib, and G. S. Cooper, “Unde rsta nding the epidemiology a nd progression of s ys temic lupus erythematosus,” Seminars in Arthritis and Rheumatism, vol. 39, pp. 257–268, 2010.
[4]
G. Bertsias, J. P. A. Ioannidis, J. Boletis et al., “EULAR recommendations for the management of SLE,” Annals of the Rheumatic Diseases, vol. 67, no. 2, pp. 195–205, 2008.
[5]
P. K. Chugh and B. S. Kalra, “Belimumab: targeted therapy for lupus,” International Journal of Rheumatic Diseases, vol. 16, pp. 4–13, 2013.
[6]
L. Lan, F. Han, and J. H. Chen, “Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis,” Journal of Zhejiang University-Science B, vol. 13, pp. 731–744, 2012.
[7]
J. H. Stone, P. A. Merkel, R. Spiera et al., “Rituximab versus cyclophosphamide for ANCA-associated vasculitis,” The New England Journal of Medicine, vol. 363, no. 3, pp. 221–232, 2010.
[8]
R. B. Jones, J. W. C. Tervaert, T. Hauser et al., “Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis,” The New England Journal of Medicine, vol. 363, no. 3, pp. 211–220, 2010.
[9]
J. T. Merrill, C. M. Neuwelt, D. J. Wallace 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 and Rheumatism, vol. 62, no. 1, pp. 222–233, 2010.
[10]
B. H. Rovin, R. Furie, K. Latinis, et al., “Efficacy and safety of rituximab in patients with active proliferative lup us nephritis: the lup us nep hritis assessme nt with rituximab study,” Arthritis & Rheumatism, vol. 64, no. 4, pp. 1215–1226, 2012.
[11]
L. F. Pinto, C. J. Velásquez, C. Prieto, L. Mestra, E. Forero, and J. D. Márquez, “Rituximab induces a rapid and sustained remission in Colombian patients with severe and refractory systemic lupus erythematosus,” Lupus, vol. 20, no. 11, pp. 1219–1226, 2011.
[12]
F. Catapano, A. N. Chaudhry, R. B. Jones, K. G. C. Smith, and D. W. Jayne, “Long-term efficacy and safety of rituximab in refractory and relapsing systemic lupus erythematosus,” Nephrology, Dialysis, Transplantation, vol. 25, no. 11, pp. 3586–3592, 2010.
[13]
E. M. Tan, A. S. Cohen, and J. F. Fries, “The 1982 revised criteria for the classification of systemic lupus erythrematosus,” Arthritis and Rheumatism, vol. 25, no. 11, pp. 1271–1277, 1982.
[14]
M. Mosca and S. Bombardieri, “Assessing remission in systemic lupus erythematosus,” Clinical and Experimental Rheumatology, vol. 24, no. 6, supplement 43, pp. S100–S104, 2006.
[15]
C. Bombardier, D. D. Gladman, M. B. Urowitz, D. Caron, and C. H. C. Chi Hsing Chang, “Derivation of the SLEDAI: a disease activity index for lupus patients,” Arthritis and Rheumatism, vol. 35, no. 6, pp. 630–640, 1992.
[16]
L. F. Ramírez, C. A. Ca？as, G. J. Tobon, F. Bonilla, and C. D. Serrano, “Successful desensitizationtorituximab in four patients with autoinmune diseases,” in Proceedings of the EAACI-WAO congress, Abstract 498, 2013.
[17]
C. Galarza, D. Valencia, G. J. Tobón et al., “Should rituximab be considered as the first-choice treatment for severe autoimmune rheumatic diseases?” Clinical Reviews in Allergy and Immunology, vol. 34, no. 1, pp. 124–128, 2008.
[18]
R. Guzman Moreno, “B-cell depletion in autoimmune diseases. Advances in autoimmunity,” Autoimmunity Reviews, vol. 8, no. 7, pp. 585–590, 2009.
[19]
C. Galarza-Maldonado, M. R. Kourilovitch, J. E. Molineros et al., “The administration of low doses of rituximab followed by hydroxychloroquine, prednisone and low doses of mycophenolate mofetil is an effective therapy in Latin American patients with active systemic lupus erythematosus,” Autoimmunity Reviews, vol. 10, no. 2, pp. 108–111, 2010.
[20]
R. Cartin-Ceba, J. M. Golbin, K. A. Keogh, et al., “Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): ten year experience at asingle center,” Arthritis and Rheumatism, vol. 64, pp. 3770–3778, 2012.
