SNOWMASS, COLO. – Most American physicians who treat systemic lupus erythematosus have been overly slow to adopt the low-dose, less toxic minipulse intravenous cyclophosphamide regimen pioneered in the landmark Euro-Lupus Nephritis Trial, Dr. David Wofsy said at a symposium sponsored by the American College of Rheumatology.
“I think we should move away from traditional, [National Institutes of Health]-style cyclophosphamide. If you're going to use cyclophosphamide, I would favor using [the Euro-Lupus Nephritis Trial cyclophosphamide regimen] at this point without hesitation,” said Dr. Wofsy, professor of medicine at the University of California, San Francisco, and a former ACR president.
For many years, the standard therapy for lupus nephritis has been the high-dose pulse intravenous cyclophosphamide (Cytoxan) regimen that has shown to be effective in an NIH trial. This regimen typically involves dosing monthly for 6 months at 0.5-1.0 g/m
In the ELNT, investigators led by Dr. Frederic A. Houssiau of Catholic University of Louvain, Brussels, demonstrated that a more modest cyclophosphamide regimen can achieve the same efficacy with fewer adverse effects (Arthritis Rheum. 2004;50:3934-40).
The European minipulse regimen consists of six pulses of 500 mg given at 2-week intervals, followed by azathioprine. Patients tend to be deeply grateful to be done with cyclophosphamide after just 12 weeks.
Some American physicians have criticized the ELNT because its Northern European patient population isn't representative of the lupus patients they see. But, according to Dr. Wofsy, the ELNT is actually a much better trial methodologically than the NIH study upon which high-dose pulse therapy is based. “My own feeling is that it's time to begin using cyclophosphamide in a gentler way. These [ELNT] data support that strongly,” he continued.
Patients and physicians alike look longingly at the bursting-full SLE drug development pipeline, eager for the day when they can finally discard cyclophosphamide in favor of agents that are less toxic and/or more effective. But there is reason to believe that cyclophosphamide may continue to play an important role in the coming biologic therapy era.
Preliminary evidence suggests at least two of the investigational biologics–rituximab (Rituxan) and atacicept–may have unique synergistic benefit when used with cyclophosphamide. This synergistic effect isn't present when either biologic is combined with mycophenolate mofetil (CellCept), Dr. Wofsy said.