Complete response rates better with monthly IV cyclophosphamide than with high drug doses.
BOSTON—The traditional cyclophosphamide regimen for lupus nephritis recommended by the National Institutes of Health (NIH) is superior to high-dose immunoablative cyclophosphamide, a recent study suggests.
The traditional regimen consists of monthly IV cyclophosphamide (500-1,000 mg/m2) for six months followed by quarterly IV cyclophosphamide for another two years. This has been recently shown to lead to a six-month complete response in only about 5.8% of patients with lupus nephritis. It has been suggested that high-dose immunoablative cyclophosphamide (HDIC) therapy (200 mg/kg) for four days, alone or with stem cell rescue therapy, may be a potential alternative.
The study, which was performed by Tareq Abou-Khamis, MD, chief resident at Good Samaritan Hospital in Baltimore, and supervised by Michelle Petri, MD, at Johns Hopkins Hospital in Baltimore, compared the two regimens in 29 patients followed for up to eight years. The patients had a mean age of 30.8 years; 83% were female; 52% were African-American and 31% were Caucasian. Eleven patients received MIC and eighteen received HDIC. The researchers defined a complete response as a normal glomerular filtration rate, normal urine sediment, and urine protein excretion below 500 mg/24 hours.
At 12 months, 64% of MIC recipients achieved a complete response compared with only 22% on HDIC. In addition, 91% of MIC-treated patients maintained a complete response over the entire follow-up period compared with 50% of the HDIC group.
The study also showed that 73% of MIC-treated patients achieved a urine protein of less than 0.5 g/day in one year compared with 39% of HDIC recipients. All MIC-treated patients maintained these urine protein levels compared with 72% of the HDIC group. Furthermore, 73% of MIC recipients achieved a urine protein below 0.3 g/day in one year versus only 28% of HDIC-treated patients.
The study showed that patients aged 18-29 achieved a complete response and maintained a urine protein under 0.5 g/day more often than patients aged 30-59.
Study results strongly suggest that the initial cyclophosphamide regimen for lupus nephritis should remain the traditional NIH monthly one, with HDIC (with or without stem cell rescue) reserved for rescue, according to the researchers. “Patients probably have to stick to their NIH regimens,” he said.
“This is unfortunate. We were hoping that by giving high-dose cyclophosphamide for just four days we could avoid giving patients prolonged cytotoxic medications but this study showed that the NIH method is still the better method.”