Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis

Background The optimal therapy for immunoglobulin A nephropathy (IgAN) remains uncertain. Leflunomide (LEF) is an immunosuppressive drug which may reduce deposition of glomerular autoantibodies and immune complexes. Several clinical trials were designed to evaluate the efficacy of LEF, but their results were controversial. Methods Ovid Medline, Embase, the Cochrane Library, PubMed, and CNKI were systematically searched. Search terms included (“glomerulonephritis” OR “nephritis”) AND (“immunoglobulin A” OR “IgA”) AND “leflunomide”. Studies in which patients were diagnosed with IgAN based on renal biopsy were included. Studies needed to report clinical outcomes via either short- or long-term clinical examination, remission rate, or complication rate. Results Forty-four studies encompassing 1802 patients were included, of which 35 were randomized controlled trials. Results of 24 h post-treatment urine protein tests and serum creatinine tests were significantly lower in patients treat with LEF and corticosteroids (CS) or valsartan (ACEI) (CS + LEF or CS + ACEI) compared with patients treated with CS or ACEI alone ( P < 0.05). More patients treated with CS + LEF (31.2%) achieved complete remission (CR) than patients treated with CS alone (22.2%) (RR = 0.71, 95% CI 0.59–0.85, P < 0.05). Although there was no significant difference in CR between patients treated with cyclophosphamide and CS (CS + CTX) and those treated with CS + LEF, the complication rate in the former group was higher (28.4%) than in the latter one (11.4%) (RR = 2.46, 95% CI 1.47–4.13, P < 0.005). Conclusion LEF appears to improve renal function while decreasing loss of urine protein. Combination regimens including LEF were better and safer compared with CS or ACEI alone or combinations including CTX.