medwireNews: Leflunomide, a DMARD used in the treatment of rheumatoid arthritis, is noninferior to azathioprine for the prevention of kidney flares in people with lupus nephritis, Chinese researchers report.
Writing in the Annals of the Rheumatic Diseases, Chunde Bao (Shanghai Jiao Tong University School of Medicine) and co-authors say their findings suggest that the drug “may provide a new candidate for maintenance therapy” in these patients.
Their study included 270 individuals with biopsy-confirmed active lupus nephritis from seven Chinese rheumatology centers who were initially given induction therapy with intravenous cyclophosphamide plus glucocorticoids for 6 to 9 months.
At the end of induction, the 215 patients who achieved a complete or partial response were randomly assigned to receive 36 months of maintenance therapy with leflunomide 20 mg/day (n=108) or azathioprine 50 mg/day increasing to 100 mg/day (n=107), each in combination with prednisone or equivalent (maximum 10 mg/day).
During the maintenance period, 15.7% of people given leflunomide and 17.8% of those receiving azathioprine experienced a kidney flare, after a median of 16 months and 14 months, respectively. The difference between the two groups was not statistically significant and fell within the noninferiority margin of 12.0%.
The proportion of patients who maintained a complete response over 36 months was also similar between the two groups, at 56.4% with leflunomide and 54.2% with azathioprine, as were the changes from baseline in 24-hour proteinuria, serum creatinine, serum albumin, estimated glomerular filtration rate, and SLEDAI.
One patient in the leflunomide group and two in the azathioprine group had an extrarenal flare, while 56.5% and 58.9%, respectively, experienced adverse events (AEs).
Of note, there were no serious AEs in either group, and the authors say that discontinuation rates as a result of AEs were “similar” between the two treatments, at 1.9% for leflunomide and 4.7% for azathioprine.
Bao et al also report extended follow-up data for a subgroup of patients who maintained remission and tapered treatment. In all, 44.4% patients in the leflunomide group and 39.3% of those in the azathioprine continued using study drugs for more than 4 years.
After 5 years, a respective 20.4% and 14.0% remained on treatment, while at 6 years the corresponding proportions were 9.3% and 8.4%.
The investigators say that there were no cases of kidney failure throughout the study, and just one patient discontinued azathioprine as a result of intolerance during the extended follow-up, which suggests “the long-term safety” of both drugs.
Bao and team conclude that “prolonged, double-blind, placebo-controlled follow-up studies in larger and more diverse patient populations are needed to further verify the long-term effect of leflunomide in the maintenance therapy of [lupus nephritis].”
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Ann Rheum Dis 2022; doi:10.1136/ard-2022-222486