ATLANTA—Enteric-coated mycophenolate sodium (EC-MPS) in combination with steroids is a viable therapy for lupus nephritis, according to an Italian study presented at the American College of Rheumatology annual meeting.
The overall clinical results indicated a reduced dose of oral prednisolone may provide a significant clinical benefit with fewer adverse effects.
“The use of steroids is one of the reasons for long-term damage. The chronic administration of steroids, especially at high dosage, is clearly related to cardiovascular disease, hypertension, osteoporosis, osteonecrosis, diabetes, glaucoma and so it is very important to try to reduce the use of steroids in lupus patients,” said lead investigator Andre Doria, MD, Associate Professor of Rheumatology at the University of Padova, Padova, Italy. “The results [of the new study] were quite good and other clinicians can start using this regimen.”
The study was designed to compare the non-inferior efficacy and safety of EC-MPS using two oral prednisolone regimens—standard dose (SD) or reduced dose (RD)—for the induction of remission of a lupus nephritis flare. Mycophenolate mofetil (MMF) has been shown to be an effective therapy for lupus nephritis and to reduce the need for corticosteroids. However, it is associated with gastrointestinal (GI) adverse events. EC-MPS is equivalent in efficacy to MMF, but produces a better GI severity score compared with MMF.
The investigators conducted a 24-week exploratory, multi-center, open-label study of 81 patients experiencing a lupus nephritis flare. All patients received EC-MPS 1,440 mg a day for the first 14 days, followed by 2,160 mg a day for the remaining 22 weeks, and intravenous methylprednisolone (0.5 g/day) for the first three days. Patients were randomized to either SD or RD prednisolone (42 patients and 39 patients, respectively). Those in the RD group received 50% lower doses of the drug. The primary endpoint was the proportion of patients with complete response after 24 weeks, defined as a urine protein:creatinine ratio below 0.5 with normalized urine sediment, and serum creatinine within 10% of normal. Investigators defined a partial response as a reduction of the urine protein/creatinine ratio of at least 50% from baseline and stable or improved serum creatinine.
The two groups had comparable baseline characteristics. The mean age of the patients was 74 years and 81% were female. After 24 weeks, a similar proportion of patients achieved complete response in both groups (19% for SD and 18% for RD). However, non-inferiority was not demonstrated. A higher proportion of patients in the SD group than the RD group achieved a partial response (48% vs. 33%).
Overall, the researchers found that index scores decreased in both groups. The British Isles Lupus Assessment Group index showed a mean change from baseline of -8.6 for SD versus -9.4 for RD. The Systemic Lupus Erythematosus Disease Activity Index was -10.4 for SD versus -9.4 for RD. In addition, the estimated glomerular filtration rate (mL/min/1.73 m2) increased significantly more in the RD than the SD group (15.2 vs. 9.0).
Two deaths occurred, both in the SD group. The incidence of serious adverse events was 16.7% for SD versus 10.3% for RD. In the SD group, one patient discontinued the study because of an adverse event; in the RD group, four patients discontinued the study (two because of adverse events, one because of an unsatisfactory therapeutic effect, and one because of administrative problems).
The researchers concluded that reduced corticosteroid dosing in the presence of concomitant EC-MPS may offer tolerability benefits similar to that of a standard corticosteroid regimen while maintaining efficacy in the management of lupus nephritis flare.