Full Text:   <5067>

CLC number: R758.62

On-line Access: 2012-09-04

Received: 2012-02-27

Revision Accepted: 2012-04-16

Crosschecked: 2012-08-09

Cited: 16

Clicked: 7921

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2012 Vol.13 No.9 P.731-744


Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis

Author(s):  Lan Lan, Fei Han, Jiang-hua Chen

Affiliation(s):  Department of Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

Corresponding email(s):   chenjianghua@zju.edu.cn

Key Words:  Systemic lupus erythematosus, Rituximab, Meta-analysis

Lan Lan, Fei Han, Jiang-hua Chen. Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis[J]. Journal of Zhejiang University Science B, 2012, 13(9): 731-744.

@article{title="Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis",
author="Lan Lan, Fei Han, Jiang-hua Chen",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis
%A Lan Lan
%A Fei Han
%A Jiang-hua Chen
%J Journal of Zhejiang University SCIENCE B
%V 13
%N 9
%P 731-744
%@ 1673-1581
%D 2012
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1200057

T1 - Efficacy and safety of rituximab therapy for systemic lupus erythematosus: a systematic review and meta-analysis
A1 - Lan Lan
A1 - Fei Han
A1 - Jiang-hua Chen
J0 - Journal of Zhejiang University Science B
VL - 13
IS - 9
SP - 731
EP - 744
%@ 1673-1581
Y1 - 2012
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1200057

Objective: To review the efficacy and safety of rituximab therapy for systemic lupus erythematosus (SLE).Methods: We searched for randomized controlled trails and observational studies that evaluated the effect of rituximab based on the systemic lupus erythematosus disease activity index (SLEDAI), British Isles lupus assessment group index (BILAG), urine protein levels, and the prednisolone dose, and had adequate data to calculate the mean, standard deviation (SD), and 95% confidence intervals, and to systematically review and meta-analyze observational studies with fixed effects model or random effects model. Results: We included 2 randomized controlled studies and 19 observational clinical studies. We summarized the data from the 19 observational studies, analyzed the heterogeneity of the literature, and then used fixed effect model or random effect model for statistical analysis. The SLEDAI, BILAG, and urine protein levels and the prednisolone dosage were decreased after rituximab treatment, and the decreases in the BILAG, urine protein levels, and the prednisolone dose were found to be significant (P<0.05), when compared with baseline level. rituximab’s adverse effects generally could be controlled with an effective dosing regimen. Conclusions: Although there are still controversies about rituximab’s treatment on SLE, but our study had showed that rituximab had favorable effects on refractory lupus. The long-term efficacy and safety of rituximab require further study.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Arce-Salinas, C.A., Rodríguez-García, F., Gómez-Vargas, J.I., 2012. Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis. Rheumatol. Int., 32(5):1245-1249.

[2]Bingham, C.O., Looney, R.J., Deodhar, A., Halsey, N., Greenwald, M., Codding, C., Trzaskoma, B., Martin, F., Agarwal, S., Kelman, A., 2010. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum., 62(1):64-74.

[3]Calabrese, L.H., Molloy, E.S., Huang, D., Ransohoff, R.M., 2007. Progressive multifocal leukoencephalopathy in rheumatic diseases: evolving clinical and pathologic patterns of disease. Arthritis Rheum., 56(7):2116-2128.

[4]Catapano, F., Chaudhry, A.N., Jones, R.B., Smith, K.G., Jayne, D.W., 2010. Long-term efficacy and safety of rituximab in refractory and relapsing systemic lupus erythematosus. Nephrol. Dial. Transplant., 25(11):3586-3592.

[5]Emery, P., Deodhar, A., Rigby, W.F., Isaacs, J.D., Combe, B., Racewicz, A.J., Latinis, K., Abud-Mendoza, C., Szczepanski, L.J., Roschmann, R.A., et al., 2010. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann. Rheum. Dis., 69(9):1629-1635.

[6]Furie, R., Looney, R.J., Rovin, B., Latinis Kevin, M., Appel, G., Sanchez-Guerrero, J., 2009. Efficacy and safety of rituximab in subjects with active proliferative lupus nephritis (LN): results from the randomized, double-blind phase III LUNAR study [abstract]. Arthritis Rheum, 60(s10):1149.

[7]Gunnarsson, I., Sundelin, B., Jónsdóttir, T., Jacobson, S.H., Henriksson, E.W., van Vollenhoven, R.F., 2007. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum., 56(4):1263-1272.

[8]Houssiau, F.A., Vasconcelos, C., D′Cruz, D., 2002. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum., 46(8):2121-2131.

[9]Lateef, A., Lahiri, M., Teng, G.G., Vasoo, S., 2010. Use of rituximab in the treatment of refractory systemic lupus erythematosus: Singapore experience. Lupus, 19(6):765-770.

[10]Leandro, M.J., Edwards, J.C., Cambridge, G., Ehrenstein, M.R., Isenberg, D.A., 2002. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum., 46(10):2673-2677.

[11]Leandro, M.J., Cambridge, G., Edwards, J.C., Ehrenstein, M.R., Isenberg, D.A., 2005. Isenberg, B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology, 44(12):1542-1545.

[12]Levine, T.D., Pestronk, A., 1999. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using rituximab. Neurology, 52(8):1701-1704.

[13]Marks, S.D., Patey, S., Brogan, P.A., Hasson, N., Pilkington, C., Woo, P., Tullus, K., 2005. B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus. Arthritis Rheum., 52(10):3168-3174.

[14]Melander, C., Sallée, M., Trolliet, P., Candon, S., Belenfant, X., Daugas, E., Rémy, P., Zarrouk, V., Pillebout, E., Jacquot, C., et al., 2009. Rituximab in severe lupus nephritis: early B-cell depletion affects long-term renal outcome. Clin. J. Am. Soc. Nephrol., 4(3):579-587.

[15]Merrill, J.T., Buyon, J.P., Furie, R.A., Latinis, L.M., Gordon, C., Hsieh, H.J., Brunetta, P., 2011. Assessment of flares in lupus patients enrolled in a phase II/III study of rituximab (EXPLORER). Lupus, 20(7):709-716.

[16]Molloy, E.S., 2011. PML and rheumatology: the contribution of disease and drugs. Cleve. Clin. J. Med., 78(s2):S28-S32.

[17]Molloy, E.S., Calabrese, L.H., 2010. Progressive multifocal leukoencephalopathy in patients with rheumatic diseases: are patients with systemic lupus erythematosus at particular risk? Autoimmun. Rev., 8(2):144-146.

[18]Murray, E., Perry, M., 2010. Off-label use of rituximab in systemic lupus erythematosus: a systematic review. Clin. Rheumatol., 29(7):707-716.

[19]Nwobi, O., Abitbol, C.L., Chandar, J., Seeherunvong, W., Zilleruelo, G., 2008. Rituximab therapy for juvenile-onset systemic lupus erythematosus. Pediatr. Nephrol., 23(3):413-419.

[20]Odendahl, M., Jacobi, A., Hansen, A., Feist, E., Hiepe, F., Burmester, G.R., 2000. Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J. Immunol., 165(10):5970-5979.

[21]Pepper, R., Griffith, M., Kirwan, C., Levy, J., Taube, D., Pusey, C., Lightstone, L., Cairns, T., 2009. Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids. Nephrol. Dial. Transplant., 24(12):3717-3723.

[22]Pinto, L.F., Velásquez, C.J., Prieto, C., Mestra, L., Forero, E., Márquez, J.D., 2011. Rituximab induces a rapid and sustained remission in Colombian patients with severe and refractory systemic lupus erythematosus. Lupus, 20(11):1219-1226.

[23]Podolskaya, A., Stadermann, M., Pilkington, C., Marks, S.D., Tullus, K., 2008. B cell depletion therapy for 19 patients with refractory systemic lupus erythematosus. Arch. Dis. Child., 93(5):401-406.

[24]Ramos-Casals, M., Díaz-Lagares, C., Khamashta, M.A., 2009. Rituximab and lupus: good in real life, bad in controlled trials. Comment on the article by Lu et al. Arthritis Rheum., 61(9):1281-1282.

[25]Ramos-Casals, M., García-Hernández, F.J., de Ramón, E., Callejas, J.L., Martínez-Berriotxoa, A., Pallarés, L., Caminal-Montero, L., Selva-O′Callaghan, A., Oristrell, J., Hidalgo, C., et al., 2010. Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Clin. Exp. Rheumatol., 28(4):468-476.

[26]Reff, M.E., Carner, K., Chambers, K.S., Chinn, P.C., Leonard, J.E., Raab, R., Newman, R.A., Hanna, N., Anderson, D.R., 1994. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood, 83(2):435-445.

[27]Rigby, W., Ferraccioli, G., Greenwald, M., Zazueta-Montiel, B., Fleischmann, R., Wassenberg, S., Ogale, S., Armstrong, G., Jahreis, A., Burke, L., et al., 2011. Effect of rituximab on physical function and quality of life in patients with rheumatoid arthritis previously untreated with methotrexate. Arthritis Care Res., 63(5):711-720.

[28]Roccatello, D., Sciascia, S., Rossi, D., Alpa, M., Naretto, C., Baldovino, S., Menegatti, E., La Grotta, R., Modena, V., 2011. Intensive short-term treatment with rituximab, cyclophosphamide and methylprednisolone pulses induces remission in severe cases of SLE with nephritis and avoids further immunosuppressive maintenance therapy. Nephrol. Dial. Transplant., 26(12):3987-3992.

[29]Scott, S.D., 1998. Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma. Cancer Pract., 6(3):195-197.

[30]Shan, D., Ledbetter, J.A., Press, O.W., 2000. Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells. Cancer Immunol. Immunother., 48(12):673-683.

[31]Sutter, J.A., Kwan-Morley, J., Dunham, J., Du, Y.Z., Kamoun, M., Albert, D., Eisenberg, R.A., Luning Prak, E.T., 2008. A longitudinal analysis of SLE patients treated with rituximab (anti-CD20): factors associated with B lymphocyte recovery. Clin. Immunol., 126(3):282-290.

[32]Tamimoto, Y., Horiuchi, T., Tsukamoto, H., Otsuka, J., Mitoma, H., Kimoto, Y., Nakashima, H., Muta, K., Abe, Y., Kiyohara, C., et al., 2008. A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans’ syndrome: immunological analysis of B cells, T cells and cytokines. Rheumatology, 47(6):821-827.

[33]Terrier, B., Amoura, Z., Ravaud, P., Hachulla, E., Jouenne, R., Combe, B., Bonnet, C., Cacoub, P., Cantagrel, A., de Bandt, M., et al., 2010. Safety and efficacy of rituximab in systemic lupus erythematosus. Arthritis Rheum., 62(8):2458-2466.

[34]Thatayatikom, A., White, A.J., 2006. Rituximab: a promising therapy in systemic lupus erythematosus. Autoimmun. Rev., 5(1):18-24.

[35]Tokunaga, M., Saito, K., Kawabata, D., Imura, Y., Fujii, T., Nakayamada, S., Tsujimura, S., Nawata, M., Iwata, S., Azuma, T., et al., 2007. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann. Rheum. Dis., 66(4):470-475.

[36]Tony, H.P., Burmester, G., Schulze-Koops, H., Grunke, M., Henes, J., Kötter, I., Haas, J., Unger, L., Lovric, S., Haubitz, M., et al., 2011. Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID). Arthritis Res. Ther., 13(3):R75.

[37]Turner-Stokes, T., Lu, T.Y., Ehrenstein, M.R., Giles, I., Rahman, A., Isenberg, D.A., 2011. The efficacy of repeated treatment with B-cell depletion therapy in systemic lupus erythematosus: an evaluation. Rheumatology, 50(8):1401-1408.

[38]Vigna-Perez, M., Hernández-Castro, B., Paredes-Saharopulos, O., Portales-Pérez, D., Baranda, L., Abud-Mendoza, C., González-Amaro, R., 2006. Clinical and immunological effects of rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res. Ther., 8(3):R83.

[39]Vital, E.M., Dass, S., Buch, M.H., Henshaw, K., Pease, C.T., Martin, M.F., Ponchel, F., Rawstron, A.C., Emery, P., 2011. B cell biomarkers of rituximab responses in systemic lupus erythematosus. Arthritis Rheum., 63(10):3038-3047.

[40]Waldman, M., Appel, G.B., 2006. Update on the treatment of lupus nephritis. Kidney Int., 70(8):1403-1412.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE