Clinical trial supports better treatment for lupus nephritis

Treating lupus patients suffering from kidney inflammation with a medicine known as mycophenolate mofetil may be more effective in inducing remission than treating them with the standard regimen of intravenous cyclophosphamide (Cytoxan), a new clinical trial indicates.

The study, published in Thursday’s issue (Nov. 24) of the New England Journal of Medicine, also showed that mycophenolate mofetil produced fewer complications, researchers found.

Such results could be an important step forward in protecting patients from Cytoxan’s side effects, including loss of child-bearing ability, the doctors say. Since 90 percent of lupus patients are women, and the average age when the disease is diagnosed is 32 years old, loss of fertility remains an important concern.

Authors of the report include Drs. Ellen M. Ginzler, chief of rheumatology at SUNY Downstate Medical Center in Brooklyn, and Mary Anne Dooley, associate professor of medicine and a Thurston Arthritis Research Center investigator at the University of North Carolina at Chapel Hill School of Medicine.

“This is the first nationwide randomized clinical trial comparing the newer agent, approved for about 10 years for kidney transplant patients, with the long-time standard of care, which has been Cytoxan,” said Dooley, who helped design the FDA orphan disease branch-funded study, get it approved and recruit medical centers and patients. “Our results are very promising, but we need to do longer follow-up to see if the new medicine produces long-lasting improvement.”

Oral mycophenolate mofetil worked faster in relieving inflamed kidneys, a condition doctors call nephritis, in half of the 140 patients enrolled in the trial, she said. At the end of the six months, patients taking it were doing significantly better than the other half, who were getting monthly intravenous doses of the standard medication.

“Lupus nephritis is a severe manifestation of lupus, which is an autoimmune disease that affects nine times as many women as men,” Dooley said. “It also is three times more likely to occur in African-Americans than in Caucasians, and it is an increasing cause of end-stage renal disease.

“Among African-American patients we see, 40 percent progress to dialysis within five years,” she said. “That’s despite being treated with Cytoxan, and so we are very motivated to find new drugs to better treat these patients.”

For unknown reasons, blacks tend to get lupus earlier in life and suffer severe kidney damage much more frequently, the UNC physician said. African patients get it, too, but not with nearly the same severity as blacks in the U.S. and Europe.

A major issue for future studies of mycophenolate mofetil will be whether it protects as well as, or better than, Cytoxan does against nephritis relapses among lupus patients, Dooley said.

In an accompanying editorial in the New England Journal of Medicine, Dr. W. Joseph McCune of the University of Michigan said, “In an era of industry-sponsored research, this investigator-initiated and investigator-directed clinical trial makes an important contribution to patient care.”

Support for the study came from the Food and Drug Administration’s Orphan Products Development program and Roche Laboratories, which provided medications.

Other researchers and institutions involved included Drs. Cynthia Aranow of SUNY Downstate Medical Center, Mimi Y. Kim of the Albert Einstein College of Medicine, Jill Buyon of New York University, Joan T. Merrill of the Oklahoma Medical Research Foundation, Michelle Petri of Johns Hopkins University School of Medicine, Gary S. Gilkeson of the Medical University of South Carolina, Daniel J. Wallace and Michael H. Weisman of Cedars-Sinai Medical Center in Los Angeles and Gerald B. Appel of Columbia University.