Experiencia con rituximab en el tratamiento de pacientes con lupus eritematoso sistémico

García-Hernández, F.J.; Díaz-Cobos, C.; Callejas-Rubio, J.L.; Ocaña-Medina, C.; Ortego-Centeno, N.; Sánchez-Román, J.; de Ramón-Garrido, E.; Camps-García, M.T.

doi:10.1016/S1699-258X(06)73016-9

Article information

Objetivo

Analizar la efectividad y tolerancia a corto plazo de la terapia con rituximab (RTX) en pacientes con lupus eritematoso sistémico (LES) y diferentes manifestaciones clínicas.

Pacientes y métodos

Se estudió a un total de 13 pacientes. El RTX fue indicado en 6 ocasiones para el tratamiento de nefritis refractaria, en 5 para el tratamiento de trombocitopenia grave, en 1 para el tratamiento de aplasia medular y en 1 para el tratamiento de vasculitis peritoneal asociada a nefritis. Los 13 pacientes fueron tratados con 4 dosis semanales de 375 mg/m2 de RTX. El tiempo medio de seguimiento fue 12±8,5 meses. Nueve pacientes experimentaron una respuesta favorable; 3 con nefropatía, 5 con trombocitopenia y 1 con vasculitis peritoneal y nefritis. El SLEDAI medio pasó de 11 a 6,5. Dos pacientes con trombocitopenia presentaron recidivas; y la respuesta al retratamiento fue buena.

Conclusiones

El presente estudio demuestra que RTX es un fármaco efectivo y seguro, a corto plazo, en el tratamiento de diferentes manifestaciones clínicas asociadas al LES.

Palabras clave:

Rituximab

Anti CD20

Lupus eritematoso sistémico

Nefritis

Trombocitopenia

Objective

To assess the short-term effectiveness and tolerance of rituximab in patients with systemic lupus erythematous and distinct clinical manifestations.

Patients and methods

Thirteen patients were studied. Rituximab (RTX) was indicated for refractory nephritis in 6 patients, severe thrombocytopenia in 5, aplastic anemia in 1 and peritoneal vasculitis associated with nephritis in 1. All patients received 4 weekly doses of 375 mg/m2 of RTX. The mean length of follow-up was 12±8.5 months. Response was favorable in 9 patients: 3 with nephritis, 5 with thrombocytopenia and 1 with peritoneal vasculitis and nephritis. The mean SLE disease activity index decreased from 11 to 6.5 points. Thrombocytopenia recurred in 2 patients, who responded well to retreatment.

Conclusions

The present study demonstrates that RTX is safe and effective as short-term therapy for distinct clinical manifestations associated with SLE.

Key words:

Rituximab

Anti CD20

Systemic lupus erythematosus

Nephritis

Thrombocytopenia

Full text is only aviable in PDF

Bibliografía

[1.]

R. Cervera, M.A. Khamashta, J. Font, G.D. Sebastiani, A. Gil, P. Lavilla, European Working Party on Systemic Lupus Erythematosus, 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 (Baltimore), 82 (2003), pp. 299-308

[2.]

O. Chan, M.J. Sclomchik.

A new role for B cells in systemic autoimmunity: B cell promote spontaneous T cell activation in MRL-lpr/lpr mice.

J Immunol, 160 (1998), pp. 51-59

Medline

[3.]

M. Odendahl, A. Jacobi, A. Hansen, E. Feist, F. Hiepe, G.R. Burmester, et al.

Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus.

J Immunol, 165 (2000), pp. 5970-5979

Medline

[4.]

M.E. Reff, K. Carner, K.S. Chambers, P.C. Chinn, J.E. Leonard, R. Raab, et al.

Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20.

Blood, 83 (1994), pp. 435-445

Medline

[5.]

J.C. Edwards, L. Szczepanski, J. Szechinski, A. Filipowicz-Sosnowska, P. Emery, D.R. Close, et al.

Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.

N Engl J Med, 350 (2004), pp. 2572-2581

http://dx.doi.org/10.1056/NEJMoa032534 | Medline

[6.]

Germing U, Sohngen D, Quabeck K, Aul C. Treatment of relapsed idiopathic thrombocytopenic purpura with the anti-CD20 monoclonal antibody rituximab: a pilot study. Giagounidis AA, Anhuf J, Schneider Eur J Haematol. 2002;69:95-100.

[7.]

S. Berentsen, E. Ulvestad, B.T. Gjertsen, H. Hjorth-Hansen, R. Langholm, H. Knutsen, et al.

Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients.

Blood, 103 (2004), pp. 2925-2928

http://dx.doi.org/10.1182/blood-2003-10-3597 | Medline

[8.]

K.A. Keogh, M.E. Wylam, J.H. Stone, U. Specks.

Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis.

Arthritis Rheum, 52 (2005), pp. 262-268

http://dx.doi.org/10.1002/art.20718 | Medline

[9.]

P. Lamprecht, C. Lerin-Lozano, H. Merz, R.H. Dennin, A. Gause, J. Voswinkel, et al.

Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis.

Ann Rheum Dis, 62 (2003), pp. 1230-1233

Medline

[10.]

A. Pestronk, J. Florence, T. Miller, R. Choksi, M.T. Al-Lozi, T.D. Levine.

Treatment of IgM antibody associated polyneuropathies using rituximab.

J Neurol Neurosurg Psychiatry, 74 (2003), pp. 485-489

Medline

[11.]

P. Ruggenenti, C. Chiurchiu, V. Brusegan, M. Abbate, A. Perna, C. Filippi, et al.

Rituximab in idiopathic membranous nephropathy: a one-year prospective study.

J Am Soc Nephrol, 14 (2003), pp. 1851-1857

Medline

[12.]

J. Barquero-Romero, M. Garcia Dominguez, M. Perez Miranda.

Efficacy of therapy with anti-CD20 antibody (rituximab) in a patient with autoimmune hemolytic anemia associated.

Med Clin, 124 (2005), pp. 517-518

[13.]

T.D. Levine.

Rituximab in the treatment of dermatomyositis: an open-label pilot study.

Arthritis Rheum, 52 (2005), pp. 601-607

http://dx.doi.org/10.1002/art.20849 | Medline

[14.]

E.M. Tan, A.S. Cohen, J.F. Fries, A.T. Masi, D.J. McShane, N.F. Rothfield, et al.

The 1982 revised criteria for the classification of systemic lupus erythematosus.

Arthritis Rheum, 25 (1982), pp. 1271-1277

Medline

[15.]

C. Bombardier, D.D. Gladman, M.B. Urowitz, D. Caron, C.H. Chang, Derivation of the SLEDAI.

A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE.

Arthritis Rheum, 35 (1992), pp. 630-640

Medline

[16.]

J. Gottenberg, L. Guillevin, O. Lambotte, B. Combe, Y. Allanore, A. Cantagrel, et al.

Tolerance and short-term efficacy of rituximab in 43 patients with systemic autoimmune diseases.

Ann Rheum Dis Published Online, (2004),

http://dx.doi.org/10.1136/ard.2004.029694

[17.]

R.J. Looney, J.H. Anolik, D. Campbell, R.E. Felgar, F. Young, L.J. Arend, et al.

B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab.

Arthritis Rheum, 50 (2004), pp. 2580-2589

http://dx.doi.org/10.1002/art.20430 | Medline

[18.]

R.J. Looney.

Treating human autoimmune disease by depleting B cells.

Ann Rheum Dis, 61 (2002), pp. 863-866

Medline

[19.]

M.J. Leandro, J.C. Edwards, G. Cambridge, M.R. Ehrenstein, D.A. Isenberg.

An open study of B lymphocyte depletion in systemic lupus erythematosus.

Arthritis Rheum, 46 (2002), pp. 2673-2677

http://dx.doi.org/10.1002/art.10541 | Medline

[20.]

J.H. Anolik, D. Campbell, C. Ritchlin, M. Holyst, S. Rosenfeld, C. Varnis, et al.

B lymphocyte depletion as a novel treatment for systemic lupus erythematosus (SLE): phase I/II trial of rituximab (Rituxan®) in SLE.

Arthritis and Rheumatism, 44 (2001), pp. 387S

[21.]

P.P. Sfikakis, J.N. Boletis, S. Lionaki, V. Vigklis, K.G. Fragiadaki, A. Iniotaki, et al.

Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial.

Arthritis Rheum, 52 (2005), pp. 501-513

http://dx.doi.org/10.1002/art.20858 | Medline

[22.]

Y. Cheng, R.S. Wong, Y.O. Soo, C.H. Chui, F.Y. Lau, N.P. Chan, et al.

Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone.

N Engl J Med, 349 (2003), pp. 831-836

http://dx.doi.org/10.1056/NEJMoa030254 | Medline

[23.]

N. Cooper, R. Stasi, S. Cunningham-Rundles, M.A. Feuerstein, J.P. Leonard, S. Amadori, et al.

The efficacy and safety of B-cell depletion with anti- CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura.

Br J Haematol, 125 (2004), pp. 232-239

http://dx.doi.org/10.1111/j.1365-2141.2004.04889.x | Medline

[24.]

A.L. Rose, B.E. Smith, D.G. Maloney.

Glucocorticoids and rituximab in vitro: synergistic direct antiproliferative and apoptotic effects.

Blood, 100 (2002), pp. 1765-1773

Medline

[25.]

S. Perrotta, F. Locatelli, A. La Manna, L. Cennamo, P. De Stefano, B. Nobili.

Anti-D20 monoconal antibody (Rituximab) for life-threatining autoimmune haemolytic anemia in a patient with systemic lupus erytematosus.

Br J Hematol, 116 (2002), pp. 465-467

[26.]

K. Saigal, I.C. Valenica, J. Cohen, F. Kerdel.

Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of systemic lupus erythematosus: rapid response to rituximab.

J Am Acad Dermatol, 49 (2003), pp. S283-S285

http://dx.doi.org/10.1016/S0190 | Medline

[27.]

Saito K, Nawata M, Nakayamada S, Tokunaga M, Tsukada J, Tanaka Y. Lupus. Successful treatment with anti-CD20 monoclonal antibody (rituximab) of life-threatening refractory systemic lupus erythematosus with renal and central nervous system involvement. 2003;12:798-800.

[28.]

R. Weide, J. Heymanns, A. Pandorf, H. Koppler.

Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy.

Lupus, 12 (2003), pp. 779-782

Medline

Indexed in:

Follow us:

Subscribe:

Indexed in:

Follow us:

Subscribe:

Subscribe to our newsletter