The findings are published in the November 17 edition of the New England Journal of Medicine, with Gabriel Contreras, M.D., M.P.H., professor of medicine in the Division of Nephrology and Hypertension, as the Miami-site principal investigator.
“This is a big breakthrough in the treatment of patients with lupus nephritis,” says Contreras, who initially reported in the New England Journal of Medicine in 2004 that mycophenolate mofetil, an immunosuppressive agent, is a more effective maintenance therapy than the current standard, and carries fewer side effects.
Lupus is a debilitating autoimmune disease affecting approximately 1.5 million Americans, primarily targeting young women. As the body’s immune system attacks itself, patients often suffer from arthritis, skin rash, sensitivity to light, headaches and hair loss. One of the most severe effects of lupus is kidney disease, called lupus nephritis, affecting up to half of all lupus patients. Lupus nephritis increases the risk for premature death and chronic kidney failure, a condition that may require chronic dialysis or even transplantation.
Standard therapy has been a chemotherapy drug cyclophosphamide (IVCY, or Cytoxan®), which works by regulating the immune system. Patients receive it intravenously quarterly as a maintenance treatment to reduce disease flare-ups. However, IVCY, like much chemotherapy, produces many undesirable side effects.
In a 2004 study published in the New England Journal, Contreras and collaborators found that a widely prescribed transplant medication, mycophenolate mofetil (MMF), and an older anti-rejection drug, azathioprine (AZA), both maintained control of lupus nephritis significantly better than IVCY.
This study, built off the 2004 results published by Contreras and collaborators, compares MMF to AZA. The 36-month study examined 227 patients in 71 clinics in 19 countries from North America, South America, Central America, Asia, Europe, Australia and South Africa. Contreras, who enrolled the most patients in North America, and collaborators demonstrated that MMF was significantly more effective in maintaining a renal response and in preventing a relapse than AZA in patients with lupus nephritis.
“This is a major discovery,” Contreras says, because there are very few FDA-approved treatments for lupus. “These study results can shift the paradigm away from a therapy that is not completely effective and leaves the patient coping with yet another series of health issues.”
Prednisone or corticosteroids, Plaquinel®, an antimalarial, and aspirin are a few drugs approved to treat the symptoms of lupus, but they too come with side effects such as muscle weakness and upset stomach. More importantly, they have not proven effective at treating lupus nephritis. Though it prevents relapse of lupus nephritis flare-ups, physicians have been prescribing the use of IVCY off-label because of limited research showing other options. “Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis” involved the largest pool of patients for a lupus nephritis study.
Given the breadth of patients and study results, Contreras is hopeful that pharmaceutical companies will seek the registration of mycophenolate mofetil by the FDA as the next step. “We have shown now in two studies that mycophenolate is more effective and has fewer side effects than current treatments. For this group of patients living with lupus nephritis, these findings can directly improve their quality of life.”