AMSTERDAM — A European-style low-dose intravenous cyclophosphamide regimen achieves long-term outcomes similar to the high-dose regimen popularized in National Institutes of Health-sponsored trials for the treatment of proliferative lupus nephritis, Dr. Frederic Houssiau reported at the annual European Congress of Rheumatology.
He presented mean 100-month follow-up data from the European Lupus Nephritis Trial (Euro-Lupus), in which 90 patients with proliferative lupus nephritis were randomized to low- or high-dose cyclophosphamide followed in either case by azathioprine maintenance. The 2006 Euro-Lupus report confirms the trial's standing within the lupus field as a study featuring singularly lengthy and complete follow-up.
The first Euro-Lupus analysis showed that patients on a low-dose regimen experienced half as many serious infections as did those on the high-dose NIH-type regimen. The second report identified two key variables that, when assessed 6 months into therapy, predicted which patients would have good renal outcome at 7 years follow-up: a marked drop in serum creatinine and a decline in 24-hour proteinuria to less than 1 g.
The 2006 report concluded that at 8.3 years of follow-up, 5% of participants have developed cancer, 8% have cardiovascular disease, 7% have developed end-stage renal disease, and 6% have died. Rates of all of these outcomes were similar in the high- and low-dose cyclophosphamide arms.
That would give the advantage to the low-dose regimen, which consisted of a fixed dose of 500 mg of cyclophosphamide every 2 weeks for 3 months. In addition to fewer serious infections, other advantages of low-dose therapy are its lower cost, administration via an outpatient 30-minute drip infusion, no need to monitor the nadir WBC count, and fewer side effects, said Dr. Houssiau, professor of rheumatology at the University of Louvain (Belgium) and Euro-Lupus coordinator.
A further advantage favoring the low-dose regimen were the nine live births in that study arm, a rate threefold greater than in the high-dose group, he said.
Nevertheless, cyclophosphamide—even in low-dose form—is far from an ideal therapy. One-third of Euro-Lupus participants have experienced one or more major renal flares. It seems likely that cyclophosphamide will eventually be replaced altogether by mycophenolate mofetil or other novel agents, he predicted.
Low-dose regimen patients had half as many serious infections as did those on the high-dose regimen. DR. HOUSSIAU