EULAR 2009: Intravenous Cyclophosphamide Superior to Oral Cyclophosphamide as Induction Therapy in Lupus Nephritis

Alice Goodman

June 19, 2009

June 19, 2009 (Copenhagen, Denmark) — "Real-life" studies in patients with lupus nephritis show that intravenous (IV) cyclophosphamide is superior to oral cyclophosphamide as induction therapy and that patients with end-stage renal disease (ESRD) can be safely managed with kidney transplantation. These are the conclusions of 2 separate single-center studies presented here at EULAR 2009: The Annual European Congress of Rheumatology.

In a retrospective single-center study of patients with diffuse proliferative lupus nephritis, IV cyclophosphamide was superior to oral cyclophosphamide as induction therapy.

"Our results show that IV in cyclophosphamide as induction therapy is highly beneficial in Caucasian patients, compared with oral cyclophosphamide," said lead presenter M. Ramos-Casals, MD, from the Hospital Clinic in Barcelona, Spain. "These results are similar to those in Caucasian European patients, but in contrast with studies in North American and Asian patients."

Dose, Length of Cyclophosphamide Should Be Customized

Dr. Ramos-Casals said that the dose and length of cyclophosphamide needs to be individualized according to the patient's age, sex, and ethnicity.

She explained that the response to oral cyclophosphamide in this study is different from what has been reported in the literature, which she attributed to the introduction of newer medications, such as mycophenolate, that have come into use.

The investigators reviewed the outcomes of 206 patients diagnosed with lupus nephropathy between 1979 and 2007. Mean age at diagnosis was 31 years, and renal biopsy showed class IV nephritis, the focus of the study, in 81 patients (39%). All patients were treated with prednisone and immunosuppressive drugs. Induction therapy with cyclophosphamide was given to 62 (83%) of the 81 patients as part of the therapeutic regimen. Thirty-four patients received IV cyclophosphamide, 13 received oral cyclophosphamide, and 15 did not complete cyclophosphamide induction therapy.

Remission of lupus nephritis, defined as normalization of serum creatinine, was achieved in 82% of patients who received IV cyclophosphamide, in 50% who received oral cyclophosphamide, and in 36% who did not complete cyclophosphamide induction therapy.

Patients treated with IV cyclophosphamide also had improved renal response, less renal failure, fewer infections, and fewer cytopenias than those treated with oral cyclophosphamide. Frequency of death was 0% in those who received IV cyclophosphamide, 13% in those who received oral cyclophosphamide, and 23% in those who did not complete cyclophosphamide induction therapy.

Kidney Transplantation an Alternative to Renal Replacement Therapy

In a separate study at the same center, 22 years of experience (1986 to 2008) showed that kidney transplantation was a good alternative to renal replacement therapy in systemic lupus erythematosus (SLE) patients with kidney failure due to lupus nephritis.

"In our series, we had similar rates of graft failure and survival as reported with end-stage renal disease in other populations," said Gerald Espinosa, MD, from the Hospital Clinic in Barcelona.

Two factors were associated with graft rejection: antiphospholipid antibodies (APS) and hepatitis C virus (HCV) infection. "Both of these are treatable conditions. Anticoagulation is recommended for these patients, but some reports have related anticoagulation to hemorrhagic complications, so the management of these patients is difficult," he stated.

Forty kidney transplantations were performed in 29 patients between January 1986 and December 2008. Twenty patients had a single transplant, 22 (76%) had class IV lupus nephritis, and 83% were female.

Eleven cases of graft failure were reported (6 of 9 who were HCV-positive and 5 of 20 who were HCV-negative). APS antibodies were present in 76% of graft rejections and in 17% of functional grafts. Nine patients had retransplantations; 13 of the grafts deteriorated and those patients went on to dialysis (7 were HCV-positive). Two of these patients died.

"Cyclophosphamide Works"

"The clear message is that intravenous cyclophosphamide works and still should be considered effective. The other message is that if therapy for renal lupus doesn't prevent renal failure, patients can survive with a kidney transplant. Lupus [patients are] not different from nonlupus patients with ESRD — they can be transplanted," said Martin Aringer, MD, from the University of Dresden in Germany, who chaired the SLE session where these 2 presentations were given.

Dr. Ramos-Casals, Dr. Espinosa, and Dr. Aringer have disclosed no relevant financial relationships.

EULAR 2009: The Annual European Congress of Rheumatology: Abstracts OP-0011 and OP-0013. Presented June 11, 2009.

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