The first study comparing two therapies, mycophenolate mofetil and intravenous cyclophosphamide, for the treatment of lupus nephritis in adolescents, shows that both appear safe and effective according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (also called SLE or lupus), which is a chronic inflammatory disease that can also affect the skin, joints, lungs, nervous system, and other organs of the body. The most commons symptoms are urinary frequency, weight gain, high blood pressure, and swelling around the eyes, legs, ankles, or fingers.

Some studies have shown that pediatric lupus is more severe and causes more kidney damage than adult-onset lupus. This recently led researchers to compare the safety and effectiveness of two immunosuppressants, which are medications that can decrease the immune response.

Specifically, researchers looked at mycophenolate mofetil (CellCept®)—a drug commonly used to help prevent organ rejection in people following kidney, liver or heart transplants—and cyclophosphamide (Cytoxan®), which belongs to a class of drugs known as alkylating agents that were originally developed and are still used to treat some types of cancer. The two drugs were compared as initial induction treatment for patients with active lupus nephritis.

Researchers followed 24 pediatric (adolescent) patients—pulled from a larger study group of 370 adult and pediatric patients who enrolled at 88 medical centers in 20 countries. Pediatric patients were predominately female, ranged in age from 12 to 17 years, and had suffered from lupus nephritis for one to three years.

Ten patients were randomly assigned to take mycophenolate mofetil by mouth; 14 patients were randomly assigned to take intravenous cyclophosphamide. Both groups received prednisone, which was tapered according to a predefined plan over the course of the study. Researchers defined successful treatment as a decrease in the concentration of protein in the urine, and stabilization or improvement in kidney function.

At week 24, nearly 88 percent of the patients remained in the study. One patient from each group withdrew, and one subject who had been treated with mycophenolate mofetil died. Of the 24 patients analyzed, 15 (62.5 percent) were considered successfully treated during the 24-week induction phase of the study. Of those, seven (70 percent successful) were taking mycophenolate mofetil and eight (57 percent successful) were taking cyclophosphamide. Serious side effects, most commonly infections, were reported in similar percentages among both groups.

In this first randomized, controlled trial involving children with lupus nephritis, researchers found that patients responded as well to mycophenolate mofetil as they did cyclophosphamide. In addition to these results, researchers noted that results in these pediatric patients were similar to those among patients enrolled in the corresponding adult study – although infections were more common among young patients than their adult counterparts.

“This information is important because it provides caregivers with high-quality data regarding the effectiveness of mycophenolate mofetil and cyclophosphamide for treatment of children with lupus nephritis,” explains Robert Sundel, MD; director of rheumatology, Children’s Hospital Boston, Boston, Mass. “Controlled trials in children with rheumatologic diseases are rare, forcing pediatric rheumatologists to try to extrapolate from adult studies. The fact that this study demonstrates similarities, but also some differences, in adolescents’ responses to mycophenolate mofetil and cyclophosphamide, highlights the importance of continuing to study medications in children as well as adults.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Dr. Sundel will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 5:15 – 5:30 PM on Monday, October 27, in Room 104.
Presentation Number: 1247

Mycophenolate Mofetil Compared with Intravenous Cyclophosphamide as Induction Treatment for Pediatric Lupus Nephritis: A Randomized Trial

Robert P. Sundel1, Laura Lisk2, for the Aspreva Lupus Management Study (ALMS) Group. 1Children’s Hospital, Boston, MA; 2Vifor Pharma - Aspreva, Bagshot, United Kingdom

Objectives: Systemic lupus erythematosus (SLE) in children appears to be more severe than it is in adults. Nonetheless, no randomized, controlled treatment trials have been reported in children with SLE. We therefore evaluated, in a post-hoc analysis, safety and efficacy of mycophenolate mofetil (MMF) compared to intravenous cychophosphamide (CYC) as induction treatment for adolescent patients included in this recent controlled trial of therapy for lupus nephritis (LN). The 24 subjects analysed, represent one of the largest randomised pediatric lupus nephritis cohorts ever reported.

Study Design: Patients met ACR criteria for a diagnosis of SLE and had active or active/chronic Class III, IV, or V lupus nephritis confirmed by kidney biopsy within 6 months before randomization. Patients were randomly assigned to treatment with MMF or CYC; obvious differences between medications necessitated open-label treatment. Oral MMF was increased to a target dose of 3.0 g/day by week 3. Intravenous CYC was given in monthly pulses of 0.5-1.0 g/m2, according to the modified NIH protocol. Both groups received prednisone, with a defined taper from a maximum starting dose of 60 mg/day. Response was defined as a decrease in urine protein/creatinine ratio (P/Cr), measured over 24 hours, to <3 in patients with baseline nephrotic range P/Cr (≥3), or by ≥50% in patients with sub-nephrotic baseline P/Cr (<3), and stabilization (±25%) or improvement in serum creatinine.

Results: Overall, 370 patients aged 12-75 years enrolled at 88 centers in 20 countries in the prospective, randomized, open-label, parallel group, multicenter study. Response rates were comparable for MMF and IVC, but the study did not meet its primary objective of showing superior response for MMF. Of these patients, 24 (6.5%) were <18 years old. The 24 pediatric subjects (19 female, 5 male) had a median age of 15 years (range 12-17) with lupus nephritis for a median of 1 year (range 1-3 years). Ten were randomized to receive MMF and 14 CYC. The primary efficacy endpoint in the 24-week induction phase study was achieved in 15 patients (62.5%), 7 (70%) of those receiving MMF and 8 (57.1%) of those receiving CYC. The proportions reporting serious adverse events were similar (40.0% for MMF vs 35.7% for CYC), most commonly infections [3/10 (30%) on MMF and 3/14 children (21.4%) on CYC]. At Week 24, 21 patients (87.5%) remained in the study. One in each group withdrew from the study, and one subject receiving MMF died.

Conclusions: In the first randomized, controlled trial reported with pediatric LN patients, the response rate with MMF was similar to monthly IV CYC. Results in pediatric patients were similar to those among adults enrolled in the study, though serious infections in both arms were reported more frequently in the pediatric patients.

Disclosure Block: R.P. Sundel, Clinical trial supported by Aspreva, 9; L. Lisk, Employee of Vifor Pharma - Aspreva, 3.

Source: American College of Rheumatology (ACR)