Efficacy and safety of leflunomide combined with corticosteroids for the treatment of IgA nephropathy: a Meta-analysis of randomized controlled trials

Abstract

Objective We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of leflunomide combined with corticosteroids, compared with corticosteroids alone, for IgA nephropathy. Materials and methods Studies were retrieved by searching of PubMed, Embase, Cochrane’s Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases on 11 October 2021. A random-effect model incorporating the heterogeneity was used to pool the results. The efficacy outcomes included the complete remission rate of proteinuria, overall response rate (the combined rates of patients with complete and partial remission of proteinuria), changes of urine protein excretion (UPE), serum creatinine (SCr), and estimated glomerular infiltrating rate (eGFR). Results Nineteen studies were included. Patients receiving the combined therapy had a higher complete remission rate (relative risk [RR]: 1.29, 95% CI: 1.08–1.55, p = 0.006; I 2 = 0%) and overall response rate (RR: 1.18, 95% CI: 1.10–1.26, p < 0.001, I 2 = 0%) compared to patients who received CS alone. Besides, combined therapy was associated with significantly reduced levels of UPE (mean difference [MD]: −0.30 g/24h, 95% CI: −0.43 to −0.16, p < 0.001; I 2 = 34%) and SCr (MD: −7.55 mmol/L, 95% CI: −11.06 to −4.04, p < 0.001; I 2 = 34%), and increased level of eGFR (MD: 6.51 mL/min/1.73 m 2 , 95% CI: 4.06–8.97, p < 0.001; I 2 = 0%). The incidence of adverse events was not significantly different. Conclusions Combined treatment with leflunomide and corticosteroids was more effective than corticosteroids alone for patients with IgA nephropathy.

Efficacy and safety of low-dose corticosteroids combined with leflunomide for progressive IgA nephropathy: a systematic review and meta-analysis

“…Besides that, combination protocols that include leflunomide have shown significant advantages in efficacy and safety. Lv et al [ 28 ] reported the beneficial effects of combined treatment with leflunomide and corticosteroids for IgAN. In an RCT, Cheng et al [ 15 ] demonstrated that valsartan combined with clopidogrel and leflunomide could protect renal function with minimal adverse effects.…”

“…In contrast to previous studies [ 28 ], our study focuses more on the safety and efficacy of low-dose corticosteroids combined with leflunomide in treating progressive IgA nephropathy. In addition, our study also found that the low-dose corticosteroids combined with leflunomide significantly reduced UPE and the incidence of serious adverse events, which was not mentioned in the previous study.…”

Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children

“…Two previous, really extensive meta-analyses [30,31] describing the possible role of leflunomide in IgAN, suggested its efficacy in improving renal function and decreasing proteinuria, mostly when combined with CS.…”

“…Lvet al [31], presented a different meta-analysis of19 RCTs (7 included in previous meta-analyses) including 1153 patients randomly assigned to a treatment group of the combined therapy with leflunomide and CS or CS alone. The combined treatment with leflunomide + CS is more effective than CS alone in reducing proteinuria and preserving renal function.…”