New Drugs Offer Relief for Lupus Patients with Kidney Problems

One of the more common and potentially serious complications for patients with systemic lupus erythematosus (also called SLE or lupus) is kidney involvement, called lupus nephritis. Until recently, such patients were typically prescribed cyclophosphamide, a chemotherapy drug that relieved symptoms for some, but was also accompanied by such side effects as hair loss, nausea, infection and infertility.

So when the New England Journal of Medicine reported in November 2005 that CellCept, an immune-suppression drug, worked significantly better than cyclophosphamide and with fewer side effects, there was rejoicing by patients with SLE and by some physicians. In an accompanying editorial, however, the Journal noted that CellCept (generic name: mycophenolate mofetil) would not become the standard of care until a larger, more definitive study is completed. The editorial did say that it was reasonable for doctors to prescribe the drug to patients worried about preserving fertility.

"We've been using CellCept here for at least the past two or three years," says Mary E. Cronin, MD, an Associate Professor of Medicine at the Medical College of Wisconsin, "but we've also had good results from cyclophosphamide." Dr. Cronin - a rheumatologist whose specialty areas include systemic lupus erythematosus - says CellCept is just one of a number of promising new drug treatment options being investigated for lupus nephritis patients. Dr. Cronin practices at the Froedtert & The Medical College of Wisconsin Rheumatology Clinic.

Study Not Definitive
Dr. Cronin has concerns about patients' reading too much into the New England Journal report: In addition to the fact that the study was small - just 140 patients, with 70 receiving CellCept and 70 being administered cyclophosphamide - it wasn't definitive for other reasons, she says. The patients used in the study apparently were not as severely affected by lupus nephritis as the typical patient caseload seen in a large medical center. Second, the study's findings did not concur with the experience Dr. Cronin and her colleagues have found in their patients.

"We have had better results here with intravenous cyclophosphamide," she says. "We typically use it as the drug of choice to begin with, and if the patient has a remission, we'll switch to CellCept to maintain the remission. In certain cases with patients concerned about fertility, we do use CellCept as the primary drug. If the patient is quite ill, we go directly to cyclophosphamide."

Dr. Cronin says about 50% of lupus patients do have clinical kidney disease - although not all cases are severe - and another 20% have "subclinical" kidney problems. The subclinical patients are often not diagnosed, she says, and if suspected would have to be referred to a nephrologist (kidney specialist) for a kidney biopsy. Symptoms of nephritis can include increased blood pressure readings, swelling of the legs, and protein in the urine, as determined by a urine test.

Lupus Symptoms Vary within Populations
Lupus is a vague and vexing autoimmune disease. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), lupus can affect many parts of the body. "Everyone reacts differently," NIAMS notes. "One person with lupus may have swollen knees and fever. Another person may be tired all the time or have kidney trouble. Someone else may have rashes. Lupus can involve the joints, the skin, the kidneys, the lungs, the heart or the brain. If you have lupus, it may affect two or three parts of your body. Usually, one person doesn't have all the possible symptoms."

NIAMS also notes that, although anyone can get lupus, 9 out of 10 people who have it are women. It is most common in women between 15 and 44 years old. African American women are three times more likely to get lupus than white women. It's also more common in Hispanic/Latino, Asian, and American Indian women. They tend to develop lupus at a younger age and have more symptoms at diagnosis, including kidney problems. African American women also tend to have more severe disease than whites, including seizures and strokes, while Hispanic/Latino patients have more heart problems.

Kidney Complications: Lupus Nephritis Trials and Treatments
For the past 30 years, chemotherapy has been the standard treatment for the kidney complications of lupus. Before cyclophosphamide was widely used, lupus patients were treated with steroids. Unlike treatments used today, patients flared earlier, and their flares lasted longer. Cyclophosphamide changed that, Dr. Cronin said.

CellCept is now being studied in a multicenter, controlled trial using a larger number of patients than were tested in the study described in the New England Journal. In addition, other drugs are currently undergoing testing in patient trials, Dr. Cronin notes. One active trial is underway at Froedtert & the Medical College, but it is no longer enrolling patients. At other sites, a monoclonal antibody drug, rituximab - originally used to treat lymphoma patients and now approved by the Food and Drug Administration (FDA) to treat rheumatoid arthritis - is being tested for its effects on lupus nephritis. "We're using it here off-label for patients with both lupus nephritis and lupus with other serious manifestations," she says.

"It's nice to have new medications for lupus," Dr. Cronin says. "It's been decades since we've had anything new to offer our patients. Finally, years of support for basic science research through the National Institutes of Health and other funding agencies have resulted in discoveries that are now bearing the fruit of new treatments. And that's giving new hope to lupus patients."

Barbara Abel
HealthLink Contributing Writer

For the latest information on clinical trials involving systemic lupus erythematosus (SLE) see the ClinicalTrials.gov website.

This article includes information from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.