New study on drugs for lupus nephritis

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New Study Published in the New England Journal of Medicine Offers Hope to Lupus Patients With Kidney Disease

MIAMI, Fla., March 3 /PRNewswire/ -- Drugs used to prevent rejection intransplant patients are proving equally valuable in the fight against lupusnephritis (lupus kidney disease), according to researchers at the Universityof Miami in a study published this week in the New England Journal of Medicine(NEJM).Lupus nephritis is the most common severe complication of the autoimmunedisease systemic lupus erythematosus (SLE). Approximately 1.5 millionAmericans have SLE and half of those will develop lupus kidney disease. Lupusnephritis increases the risk for premature death and chronic kidney failure, acondition that may require chronic dialysis or transplantation.In the study, "Sequential Therapies for Proliferative Lupus Nephritis,"researchers showed that maintenance with daily oral treatment with one of themost widely prescribed transplant medications, mycophenolate mofetil (MMF,also known as CellCept®) or the older anti-rejection drug azathioprine (AZA)was more effective and safer than the current "gold standard" therapy,intravenous quarterly pulses of the chemotherapy drug cyclophosphamide (IVCY,also known as Cytoxan®) in the long term treatment of lupus nephritis."We're very excited about our study results that demonstrate that newmaintenance treatment regimens with MMF or AZA are more effective and offer amuch lower incidence of significant adverse events than long-term IVCY," said Contreras, M.D., MPH, lead author of the NEJM study, AssociateProfessor of Medicine at the University of Miami School of Medicine andDirector of the Dialysis Unit at the Veterans Affairs Medical Center in Miami.

The most important highlights of the study include the findings that:

* Long-term IVCY was associated with a greater risk of death or chronicrenal failure than maintenance therapy with MMF or AZA

* Maintenance therapy with MMF or AZA was safer than long-term IVCY, withfewer hospitalizations, severe infections, amenorrhea andgastrointestinal side effects

Lupus patients with kidney involvement undergo periods of intense diseaseactivity known as flaring. Induction therapy is used to try to induce periodsof remission. "During flares, patients usually require higher doses ofcorticosteroids and additional pulses of IVCY, which increase the risk formore adverse events," added Dr. Contreras. "Avoidance of renal flares isimportant as flaring is known to cause damage to the kidneys, which can leadto kidney failure. Once a patient is in remission the aim of maintenancetreatment is to keep patients relapse-free."

Lower Relapse Rates SeenAnother highlight of the study included lower relapse rates. In thestudy, the rate of relapse was statistically significantly lower in the MMFgroup versus IVCY. Relapse rates in the AZA group were not significantlybetter than in the IVCY group. During maintenance therapy 40 percent relapsedin the IVCY group, 32 percent in the AZA group and 15 percent in the MMFgroup."These study results are likely to shift the treatment paradigm away fromlong-term chemotherapy drugs," said Dr. Contreras.This study was funded by a research grant from Roche, manufacturers of MMFunder the brand name CellCept®.

Study DesignThe open-label, randomized clinical trial of 59 patients with lupusnephritis included 27 African-Americans, 29 Hispanic-Americans and 3Caucasians. African-Americans and Hispanic-Americans are populations known tobe at high risk for lupus nephritis. All patients received the same inductiontherapy with monthly short-term IVCY and corticosteroids. The patients werethen randomized to one of three maintenance therapies: quarterly boluses ofIVCY, oral AZA (1-3 mg/kg/day); or MMF (500-3000 mg/day) for one to threeyears. Each group also received oral corticosteroids.The 72-months event-free cumulative probability of the composite end-point(death or chronic renal failure) was higher in the MMF (P=0.05) and AZA(P=0.009) groups compared to the IVCY group. Five patients died (4-IVCY,1-MMF) and five patients developed chronic renal failure (3-IVCY, 1-AZA, 1MMF).Thirty-one percent of the patients who achieved remission had a relapse(IVCY=8, AZA=6, MMF=3). The relapse-free cumulative probability was higher inthe MMF group compared to the IVCY group (P=0.024). Hospitalizations,amenorrhea, infections, and gastrointestinal side effects were significantlylower in the MMF and the AZA groups compared to the IVCY group."I am really encouraged by these study results, which add to the growingbody of evidence that CellCept® may be an effective treatment for lupusnephritis," said , President and CEO of the Lupus Foundation ofAmerica. "Last October, in a study presented at the American College ofRheumatology's Annual Meeting, we saw that CellCept® as induction therapywas at least equivalent and better tolerated than IVCY. Now we're seeing thatCellCept® may prove equally valuable as long-term maintenance therapy. I'mvery excited that there are now less toxic and more effective treatmentoptions emerging for the millions of people worldwide with lupus kidneydisease."

About CellCept® (mycophenolate mofetil)CellCept® (mycophenolate mofetil) is an immunosuppressant or"anti-rejection" drug to be used in combination with other immunosuppressivedrugs (cyclosporine and corticosteroids) for the prevention of rejection inpatients receiving heart, kidney and liver transplants. CellCept® receivedFDA approval for the prevention of organ rejection in kidney (May 1995), heart(February 1998), and liver (July 2000). The recommended dosages forCellCept® follow: for adult kidney transplants, 2 g daily; for pediatrickidney transplants, oral suspension 600 mg/m2; for adult heart and liver, 3 gdaily.The principal adverse events associated with the administration ofCellCept® (in combination with cyclosporine and corticosteroids intransplant patients) include diarrhea, leukopenia, sepsis and vomiting, andthere is evidence of a higher frequency of certain types of infections. Ahigher proportion of renal transplant patients in the active treatment groupsexperienced one or more opportunistic infections compared with patientsreceiving placebo. Cytomegalovirus tissue invasive disease was more commonin patients receiving 3 g/day.Increased susceptibility to infection and the possible development oflymphoma may result from immunosuppression. Only physicians experienced inimmunosuppressive therapy and management of renal, cardiac or hepatictransplant patients should use CellCept®. Patients receiving the drugshould be managed in facilities equipped and staffed with adequate laboratoryand supportive medical resources. The physician responsible for maintenancetherapy should have complete information requisite for the follow-up of thepatient.There are no adequate and well-controlled studies in pregnant women.However, CellCept® has been shown to have teratogenic effects in animals; itmay cause fetal harm when administered to a pregnant woman. Therefore,CellCept® should not be used in pregnant women unless the potential benefitjustifies the potential risk to the fetus. For full prescribing information,visit http://www.rocheusa.com/products/cellcept/pi.html.

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