Drugs Comparable for Adolescent Lupus Nephritis
Mycophenolate mofetil and cyclophosphamide found similarly effective for pediatric lupus nephritis.
SAN FRANCISCO—Lupus nephritis (LN) in adolescents responds similarly to mycophenolate mofetil (MMF) and IV cyclophosphamide, according to data reported at the American College of Rheumatology (ACR) annual meeting here.
Some studies have shown that pediatric lupus is more severe and causes more renal damage than adult-onset lupus, but no randomized, controlled treatment trials have been reported in children with systemic lupus erythematosus (SLE).
This led researchers to compare the safety and effectiveness of MMF and CYC in a post-hoc analysis of induction therapy in 24 adolescents (19 female). They had a median age of 15 years (range 12-17 years) with LN duration for a median of one year. The subjects were part of a prospective 24-week induction phase study that included 370 patients aged 12 to 75 years.
All patients met ACR criteria for SLE and had active or active/chronic Class III, IV, or V lupus nephritis, which had been confirmed by kidney biopsy within six months of randomization. Although patients were randomized to treatment with MMF or CYC, the obvious differences between the medications necessitated open-label treatment. Ten patients received MMF and 14 received CYC.
The starting dose of oral MMP was 500 mg twice daily. This was increased to 1 g twice daily in week 2 and 3 g/day by week 3. Following the modified NIH protocol, CYC was administered IV in monthly pulses of 0.5-1.0 g/m2. All patients in both groups received prednisone, with a defined taper from a maximum starting dose of 60 mg/day.
Investigators defined response as a decrease in urine protein/creatinine ratio (P/Cr) measured over 24 hours to less than 3 in patients with baseline nephrotic range proteinuria of 3 or greater P/Cr, or by 50% or greater in patients with sub-nephrotic proteinuria at baseline. Patients also had to demonstrate stabilization or improvement in serum creatinine.
The primary efficacy end point was achieved in 15 (62.5%) of the 24 patients. Among these 15 patients, seven received MMF and eight received CYC. The investigators concluded that the response rates were comparable for the two therapies. The proportions reporting serious adverse events were similar (40% for MMF vs. 35.7% for CYC). At week 24, nearly 88% of the patients remained in the study. One patient from each group withdrew, and one MMF-treated subject died.
The results in the adolescents were similar to those among the adults in the trial, except that the rate of serious infections in the pediatric cohort tended to be higher than among adults in both arms of the study.
“Some of the side effects were different,” said lead investigator Robert Sundel, MD, director of rheumatology at Children's Hospital in Boston. “Children tended to have more infections and more serious infections than adults and for us it highlighted the need for studies in pediatric patients. It is not always safe or appropriate to try to extrapolate from adult patients to pediatric patients.”