STOCKHOLM, Sweden—Adding the B-cell depleting agent Rituximab (Rituxan®, Genentech/Biogen Idec) to cyclophosphamide (CYC) appears safe and effective in patients with therapy-resistant proliferative lupus nephritis, according to a 6-month pilot study of seven patients in the April issue of Arthritis & Rheumatism.1

"For patients with proliferative lupus nephritis who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option," conclude researchers led by Iva Gunnarsson, MD, PhD, of Karolinska University Hospital at Solna, in Stockholm, Sweden.

Seven female patients with proliferative lupus nephritis were treated with rituximab in combination with CYC. Investigators performed renal biopsies before treatment and during a 6-month follow-up. They measured systemic lupus erythematosus (SLE) activity with the SLE Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index. Researchers performed immunostaining of lymphocyte subpopulations in the renal tissue before treatment and during follow-up in six of seven patients.

Six- month data show clinical and histopathologic improvement with combination therapy

Patients treated with the combination showed clinical improvements. Specifically, patients showed a reduction in SLEDAI scores from a mean of 15 to 3. Patients' anti-double-stranded DNA antibody levels dropped from a mean of 174 IU/mL to 56 IU/mL, and anti-C1q antibody levels fell from a mean of 35 units/mL to 22 units/mL.

There was an improvement in the histopathologic class of nephritis in a majority of patients on repeat renal biopsy. Patients showed a decrease in the renal activity index from 6 to 3, and 50% of patients showed a reduction in the number of CD3, CD4, and CD20 cells in the renal interstitium on repeat biopsy.

"Our study is the first to demonstrate that in most of the patients who had detectable CD20+ cells in renal tissue, a reduction of these cells was seen after treatment," the researchers write. A repopulation of peripheral B-cells occurred at the time of repeated biopsy in all but one patient, the study authors point out. Biopsies in one patient showed that B-cells are temporarily depleted from renal tissue after rituximab therapy.

"At 6 months of follow-up, all patients had responded both clinically and histopathologically to combination therapy," the researchers concluded.

Adverse events (AEs) included herpes infection, urinary tract infection, photosensitive eruption,  and neutropenic fever, which occurred in one patient after the second infusion of CYC.  Three patients had no AEs.

Combination "works beautifully" in practice

"We often give [cyclophosphamide] and rituximab  together in patients with refractory lupus nephritis," Robert G. Lahita MD, PhD,  professor of medicine at Mount Sinai Medical School, in New York, and chairman of medicine at the Jersey City Medical Center in Jersey City, New Jersey, told CIAOMed. Dr. Lahita gives the cyclophosphamide in the morning and then rituximab in the afternoon.

"It's a good alternative to refractory disease. I have had no adverse effects short of infection. We do worry about opportunistic infections, but there have been no major catastrophes," Dr. Lahita said.

"This treatment is reserved for only the sickest of the sick," he added. "Other than bone marrow transplantation, this is the end of the line, [but] it works beautifully."

Reference

1. Gunnarsson I, Sundelin B, Jónsdóttir T, et al. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum. 2007;56:1263-1272.