WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD,at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint ofwas complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.