Cyclophosphamide (CTS) prevents progression of nephritis and prolongs survi
val in (NZB x NZW)F-1 (B/W) mice and is used to treat humans with lupus nep
hritis, To compare the efficacy of CTLA4Ig with CTS and determine whether t
here is an incremental benefit to combining CTLA4Ig with CTX, we treated B/
W mice with CTS, CTLA4Ig, or both agents. In mice with mild renal disease,
treatment delayed the onset of proteinuria and prolonged survival in all gr
oups, In mice with advanced renal disease, treatment with both agents reduc
ed proteinuria in 71% of mice? whereas mice treated with either agent alone
had no such improvement. Survival was also markedly improved among mice tr
eated with both agents. Thus, combination treatment with CTX and CTLA4Ig is
more effective than either agent alone in reducing renal disease and prolo
nging survival of B/W mice with advanced nephritis, This striking reversal
of proteinuria is unprecedented in animal models of SLE.