The ideal
therapy for
lupus nephritis should reduce mortality and
end-stage renal disease in the long term, induce early response and remission, prevent flares, have minimal side-effects and not compromise fertility. It should also be active in all ethnic groups, widely available and cost effective. Despite 30 years' clinical experience, the ability of
cyclophosphamide to meet these needs is not supported by robust evidence. The first National Institutes for Health (NIH) trial in 1986 led to a shift from oral to intravenous
cyclophosphamide. The three NIH trials together then led to the dogma that high-dose intravenous
cyclophosphamide is the only
cytotoxic agent superior to
steroids alone in
lupus nephritis and to its general acceptance as the 'standard of care'. Since then, high-dose intravenous
cyclophosphamide has been shown to have no impact on survival, to be less effective in black patients and to have many side-effects, particularly an unacceptable risk of
premature menopause. The Euro-
Lupus Nephritis Trial found that low-dose intravenous
cyclophosphamide could be used as an alternative to a high-dose regimen and was associated with half as many severe
infections. Other advantages include no hospitalisation and virtually no risk of premature gonadal failure. Other studies have looked at regimens in which
cyclophosphamide is entirely replaced--for example, with
mycophenolate mofetil--and have found fewer side-effects and better
induction of remission. Intravenous
cyclophosphamide is the only
therapy with long-term data for reduction of
end-stage renal disease. As data on other
therapies accumulate, however, intravenous
cyclophosphamide might no longer be considered the standard treatment for
lupus nephritis.