Leflunomide non-inferior to azathioprine as maintenance therapy of lupus nephritis: BMJ

China: Leflunomide is not inferior to azathioprine in terms of its efficacy and safety for maintenance therapy of lupus nephritis (LN), reports a study data published in the BMJ journal Annals of the Rheumatic Diseases. 

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) and a major cause of morbidity and mortality. Approximately 50%–60% of adult patients with SLE develop kidney involvement during their illness. In addition, 10%–30% of patients with LN progress to kidney failure requiring kidney replacement therapy.

LN is a disease with significant unmet clinical needs. The initial phase of treatment for LN is the induction phase followed by a prolonged maintenance phase to achieve durable remission and limit the risk of LN flare. Mycophenolate mofetil (MMF) and azathioprine (AZA) are commonly used in maintenance therapy but long-term use of these drugs is associated with considerable toxicity and is not effective in all patients. Leflunomide(LEF) is an immunosuppressant widely used in the treatment of rheumatoid arthritis, with a good safety profile and long-term user experience. To date, there has been no study on leflunomide as maintenance therapy for LN.

Qiong Fu, Shanghai Jiao Tong University School of Medicine, China, and her team conducted a study to compare the efficacy and safety of LEF versus AZA as maintenance therapy for LN.

Investigators enrolled 270 adult patients with biopsy-confirmed active LN for the study. All patients received induction therapy with 6–9 months of intravenous cyclophosphamide plus glucocorticoids. A total of 215 patients who achieved partial or complete remission were randomly allocated to the leflunomide group (n=108) and azathioprine group (n=107). The primary efficacy endpoint was set as the time to kidney flare. Secondary outcomes included clinical parameters, extrarenal flare, and adverse effects.

Key findings of the study,

• Kidney flares were observed in 15.7% of leflunomide-treated patients and 17.8% of azathioprine-treated patients. Time to kidney flare did not statistically differ (leflunomide: 16 months vs azathioprine: 14 months).

• 24-hour proteinuria, serum creatinine, serum albumin, serum C3, and serum C4 improved similarly.

• The extrarenal flare occurred in two patients from the azathioprine group and one patient from the leflunomide group.

• The incidence of adverse events was similar in the 2 groups: leflunomide 56.5% and azathioprine 58.9%.

Investigators conclude that LEF is non-inferior to AZA in terms of effectiveness and adverse events in the long-term treatment of patients with LN. LEF may provide a new candidate for maintenance therapy in patients with LN with comparable efficacy to the standardized regimen of AZA.

Follow-up studies in larger and more diverse populations are needed to further verify the long-term effect of LEF in the maintenance therapy of LN, the authors wrote.

Reference:

Fu Q, Wu C, Dai M, et alLeflunomide versus azathioprine for maintenance therapy of lupus nephritis: a prospective, multicentre, randomised trial and long-term follow-up. Annals of the Rheumatic Diseases Published Online First: 04 July 2022. doi: 10.1136/ard-2022-222486