Medication Relieves Severe Lupus Nephritis

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Rituximab was associated with clinical improvement in women, study say.

 

Rituximab (Rituxan), a biologic agent used to treat B-cell non-Hodgkin's lymphoma, may offer a promising option for treating severe membranous lupus nephritis (MLN), according to Swedish researchers.

 

Their study of MLN patients revealed clinical benefits from the agent at six months. Repeat renal biopsies demonstrated ongoing resorption of extracapillary immune deposits, a feature generally not seen with conventional immunosuppressive MLN therapies.

 

“These patients have severe renal disease, and if you don't treat them they are at substantial risk of losing renal function over the years,” said lead investigator Iva Gunnarsson, MD, a rheumatologist and consultant in the department of rheumatology at the  Karolinska University Hospital in Stockholm. “All the patients treated with rituximab improved clinically and they had a decrease in proteinuria. They also had an increase in serum albumin and a decrease in serum creatinine.”

 

Dr. Gunnarsson and her colleagues previously have reported on the beneficial effects of rituximab therapy in a large cohort of patients with proliferative lupus nephritis.

 

They treated four female MLN patients with a protocol involving four repeated weekly infusions of rituximab in a dose of 375 mg/m2. In three of the patients, rituximab was given in combination with cyclophosphamide therapy (0.5 g/m2) administered twice, along with a time-limited increase of corticosteroids. The four patients had a mean age of 40 years and mean disease duration of eight years. All patients had documented MLN (World Health Organization class Vb) and three previously failed cyclophosphamide therapy.

 

Dr. Gunnarsson evaluated patients with the Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI), and measured serum creatinine, serum albumin, 24-hour albuminuria, and anti-dsDNA. Repeat renal biopsies were performed at seven to nine months after treatment.

With the SLE-DAI index, declines in score reflect improvement in the patient's condition. At six months, patients' SLE-DAI score decreased from 10.5 to 4.5. Serum creatinine levels decreased from 110 to 92 µmol/L, and serum albumin levels increased from 28.5 to 33.5 g/L.

 

The study also found a decrease in 24-hour albuminuria (from 4 g/day to 0.6 g/day). Anti-dsDNA antibodies were present in all patients prior to therapy and decreased significantly. On repeat biopsy, one patient converted into WHO class II, and electron microscopy showed a high resorption rate of immune deposits in the basal membrane in all patients.

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