Leflunomide noninferior to azathioprine for lupus nephritis
CHICAGO — Leflunomide was noninferior to azathioprine for the treatment of lupus nephritis with regard to efficacy and safety, and as a maintenance therapy, was associated with a lower rate of relapse and higher rate of complete remission, according to data presented at the ACR/ARHP 2018 Annual Meeting.
“We all know that lupus nephritis impacts patients’ survival, and usually we use cyclophosphamide or mycophenolate for the induction phase and guidelines recommend mycophenolate mofetil (MMF) as a thumbprint for the maintenance therapy,” Qiong Fu, MD, of Renji Hospital, Shanghai Jiaotong University School of Medicine, told attendees. “However, there are still a lot of patients who are not respondent to, or cannot tolerate, the current recommendation. In addition, Asian patients tend to respond less to MMF, but also have a higher risk for infection associated with MMF, so we need more therapeutic options for lupus nephritis patients.”
To compare the efficacy and safety of leflunomide to that of azathioprine as a maintenance therapy for lupus nephritis, Fu and colleagues studied 270 adult patients with biopsy-confirmed forms of the disease at seven Chinese rheumatology centers from 2010 to 2015. All participants received, as induction therapy, six monthly doses of IV cyclophosphamide in addition to steroids, which were tapered in accordance with protocol.
The 215 patients who achieved partial or complete remission were then randomly assigned to receive either a 20-mg daily dose of oral leflunomide or doses of oral azathioprine, which began at 50 mg per day and increased to 100 mg per day after 1 month, for 24 months. A total of 108 were treated with leflunomide, with 107 receiving azathioprine. Baseline clinical, biological and pathological characteristics did not differ between the two groups. The primary endpoint for efficacy was the rate of renal flare at 24 months. Secondary outcomes included clinical parameters, extrarenal flare and adverse effects.
According to Fu, renal flares were reported in 11.1% of patients treated with leflunomide, and in 14% of those who received azathioprine (P = .52). The difference in the time to renal flare between the groups was not statistically significant, with 9.83 months in the leflunomide cohort and 10.93 months for azathioprine (P = .241). Patients who achieved complete remission and were then treated with leflunomide demonstrated a lower risk for renal flare, with 6.7%, compared with 14.3% for azathioprine (P = .116). Complete remission rates in both groups continued to increase with time, from 60.2% to 87.7% after 24 months among those treated with leflunomide, and 71.9% to 88.7% for azathioprine.
The incidence of adverse events through 24 months was similar in both groups, with 43.5% among patients treated with leflunomide and 42.1% in the azathioprine cohort. Among the two groups, there was no significant difference in the rates of leukopenia, abnormal elevation of liver enzyme or anemia.
“Leflunomide is noninferior to azathioprine for maintenance therapy of lupus nephritis in terms of efficacy and safety profile,” Fu said. “With maintenance therapy for 2 years, a trend of lower rates of relapse, as well as higher complete remission, was observed in the leflunomide group. So, Leflunomide could be a new choice for maintenance therapy for lupus nephritis.” – by Jason Laday
Disclosure: Fu reports no relevant financial disclosures.
Fu Q. Abstract 974. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.