(Induction therapy) (antiphospholipid syndrome, APS) (systemic lupus erythematosus, SLE) (secondary APS) [1] (lupus nephritis) WHO (ESRD) [2]

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1 (antiphospholipid syndrome, APS) (systemic lupus erythematosus, SLE) (secondary APS) [1] (lupus nephritis) WHO (ESRD) [2] (WHO) (diffuse proliferative) [4] WHO [3] (Induction therapy) (active) (sclerotic) cyclophosphamide (Pulse CYC)

2 MPA pulse cyclophosphamide Chan [9] (NIH) Chan cyclophosphamide azathioprine azathioprine cyclophosphamide MMF MMF cyclophosphamide mycophenolic acid (MPA) MPA 0.75 g/m inosine monophosphate (European League Against dehydrogenase (IMPDH) guanine Lupus Nephritis Trial, ELNT trial) [12] Rheumatism) (Euro- (guanine) (salvage passway) 500 mg (cytotoxic agents) MMF azathio- prine MMF cyclo- phosphamide [5-7] MMF cyclo- phosphamide cy- clophosphamide cyclophosphamide MMF cyclo- cyclophosphamide phosphamide Mycophenolate mofetil (MMF) MMF pulse cyclophosphamide 1.2 mg/dl MMF cyclophosphamide cyclo- phosphamide cyclophospha- mide Azathioprine (AZA) cyclophosphamide cyclophosphamide AZA 1997 [10] AZA cyclophosphamide cyclophosphamide cyclosporine AZA [11] (immunoablative) cyclophosphamide [8] AZA

3 3 g TTP pulse cyclophosphamide AZA 71% ( ) 54% cyclophosphamide MMF pulse cyclophosphamide AZA (plasmapheresis) (Maintenance therapy) NIH pulse MMF cyclophosphamide Chan MMF MMF AZA ( ) ( cyclophosphamide ) pulse cyclophosphamide cyclophos- cyclophosphamide phamide NIH cyclophosphamide ELNT trial cyclophosphamide 22% 1.3 mg/dl 28% ELNT ELNT cyclophosphamide NIH ELNT cyclophosphamide cyclophosphamide Mycophenolate mofetil (MMF) cyclophosphamide [13] 2004 cyclophospha- MMF [15] mide (synchronized apheresis-cyc regimen) pulse cyclophosphamide [14]

4

5 LJP394 (Abetimus sodium) LJP394 La JollaCompany Abetimus sodium [16] Rituximab LJP394 Riquent polyethylene glycol DNA epitope ( ) DNA (anti-double strain DNA) [18,19] anti-double strain DNA LJP [17] LJP394 cyclophosphamide LJP394 cyclophosphamide 41% anti-double strain DNA IgG LJP394 LJP394 67% cyclophosphamide 62% LJP394 LJP394 (apoptosis) (phase III international trial) LJP394 LJP394 ( pulse cyclophosphamide ) MMF AZA 1. Datta SK, Kaliyaperumal A: Nucleosome-driven autoimmune response in lupus. Pathogenic T helper cell epitopes and costimulatory signals. Ann N Y Acad Sci 1997; 815: Cameron JS: Lupus nephritis. J Am Soc Nephrol 1999; 10: Weening JJ, D'Agati VD, Schwartz MM, et al: The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int 2004; 65: Houssiau FA: Management of lupus nephritis: an update. J Am Soc Nephrol 2004; 15: Austin HA, 3rd, Klippel JH, Balow JE, et al: Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314: Boumpas DT, Austin HA, 3rd, Vaughn EM, et al: Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992; 340: Gourley MF, Austin HA, 3rd, Scott D, et al: Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis: A randomized, controlled trial. Ann Intern Med 1996; 125: Petri M, Jones RJ, Brodsky RA: High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus. Arthritis Rheum 2003; 48: Chan TM, Li FK, Tang CS, et al: Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med 2000; 343: Bansal VK, Beto JA: Treatment of lupus nephritis: a metaanalysis of clinical trials. Am J Kidney Dis 1997; 29: Flanc RS, Roberts MA, Strippoli GF, et al: Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 2004; 43: Houssiau FA, Vasconcelos C, D'Cruz D, et al: Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002; 46:

6 13. Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM: A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collaborative Study Group. N Engl J Med 1992; 326: Demin AA, Sentiakova TN, Smirnov VV, Demina LM, Mamin IV: Synchronizing therapy with plasmapheresis and cyclophosphamide in rapidly progressing systemic lupus erythematosis with kidney involvement. Ter Arkh 1996; 68: Contreras G, Pardo V, Leclercq B, et al: Sequential therapies for proliferative lupus nephritis. N Engl J Med 2004; 350: Abetimus: Abetimus sodium, LJP 394. BioDrugs 2003; 17: Alarcon-Segovia D, Tumlin JA, Furie RA, et al: LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum 2003; 48: Moroni G, Tantardini F, Ponticelli C: Renal replacement therapy in lupus nephritis. J Nephrol 2003; 16: Ward MM: Outcomes of renal transplantation among patients with end-stage renal disease caused by lupus nephritis. Kidney Int 2000; 57:

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