Advertisement

Journal of Zhejiang University SCIENCE B

, Volume 13, Issue 9, pp 731–744 | Cite as

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

Article

Abstract

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.

Key words

Systemic lupus erythematosus Rituximab Meta-analysis 

CLC number

R758.62 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  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. [doi:10.1007/s00296-010-1755-0]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.25034]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.22657]PubMedCrossRefGoogle Scholar
  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. [doi:10.1093/ndt/gfq256]PubMedCrossRefGoogle Scholar
  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. [doi:10.1136/ard.2009.119933]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.26223]Google Scholar
  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. [doi:10.1002/art.22505]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.10461]PubMedCrossRefGoogle Scholar
  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. [doi:10.1177/0961203309358599]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art. 10541]PubMedCrossRefGoogle Scholar
  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. [doi:10.1093/rheumatology/kei080]PubMedCrossRefGoogle Scholar
  12. Levine, T.D., Pestronk, A., 1999. IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using rituximab. Neurology, 52(8):1701–1704. [doi:10.1212/WNL.52.8.1701]PubMedCrossRefGoogle Scholar
  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. [doi:10. 1002/art.21351]PubMedCrossRefGoogle Scholar
  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. [doi:10.2215/CJN.04030808]PubMedCrossRefGoogle Scholar
  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. [doi:10. 1177/0961203310395802]PubMedCrossRefGoogle Scholar
  16. Molloy, E.S., 2011. PML and rheumatology: the contribution of disease and drugs. Cleve. Clin. J. Med., 78(s2): S28–S32. [doi:10.3949/ccjm.78.s2.07]PubMedCrossRefGoogle Scholar
  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. [doi:10.1016/j.autrev.2008.07.006]CrossRefGoogle Scholar
  18. Murray, E., Perry, M., 2010. Off-label use of rituximab in systemic lupus erythematosus: a systematic review. Clin. Rheumatol., 29(7):707–716. [doi:10.1007/s10067-010-1387-5]PubMedCrossRefGoogle Scholar
  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. [doi:10.1007/s00467-007-0694-9]PubMedCrossRefGoogle Scholar
  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.PubMedGoogle Scholar
  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. [doi:10.1093/ndt/gfp336]PubMedCrossRefGoogle Scholar
  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. [doi:10.1177/0961203311409273]PubMedCrossRefGoogle Scholar
  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. [doi:10.1136/adc.2007.126276]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.24726]PubMedCrossRefGoogle Scholar
  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.PubMedGoogle Scholar
  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.PubMedGoogle Scholar
  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. [doi:10.1002/acr.20419]CrossRefGoogle Scholar
  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. [doi:10. 1093/ndt/gfr109]PubMedCrossRefGoogle Scholar
  29. Scott, S.D., 1998. Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin’s lymphoma. Cancer Pract., 6(3):195–197. [doi:10.1046/j.1523-5394.1998.006003195.x]PubMedCrossRefGoogle Scholar
  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. [doi:10.1007/s002620050016]PubMedCrossRefGoogle Scholar
  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. [doi:10.1016/j.clim.2007.11.012]PubMedCrossRefGoogle Scholar
  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. [doi:10.1093/rheumatology/ken071]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.27541]PubMedCrossRefGoogle Scholar
  34. Thatayatikom, A., White, A.J., 2006. Rituximab: a promising therapy in systemic lupus erythematosus. Autoimmun. Rev., 5(1):18–24. [doi:10.1016/j.autrev.2005.05.006]PubMedCrossRefGoogle Scholar
  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. [doi:10.1136/ard.2006.057885]PubMedCrossRefGoogle Scholar
  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. [doi:10.1186/ar3337]PubMedCrossRefGoogle Scholar
  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. [doi:10.1093/rheumatology/ker018]PubMedCrossRefGoogle Scholar
  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. [doi:10.1186/ar1954]PubMedCrossRefGoogle Scholar
  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. [doi:10.1002/art.30466]PubMedCrossRefGoogle Scholar
  40. Waldman, M., Appel, G.B., 2006. Update on the treatment of lupus nephritis. Kidney Int., 70(8):1403–1412. [doi:10. 1038/sj.ki.5001777]PubMedCrossRefGoogle Scholar

Copyright information

© Zhejiang University and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Kidney Disease Center, the First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina

Personalised recommendations