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; I² = 0%) and overall response rate (RR: 1.18, 95% CI: 1.10-1.26, p < 0.001, I² = 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; I² = 34%) and SCr (MD: -7.55 mmol/L, 95% CI: -11.06 to -4.04, p < 0.001; I² = 34%), and increased level of eGFR (MD: 6.51 mL/min/1.73 m², 95% CI: 4.06-8.97, p < 0.001; I² = 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.

Keywords: IgA nephropathy; Leflunomide; corticosteroids; meta-analysis; randomized controlled trials.

Figure 1.

Flowchart of database search and literature identification.

Figure 2.

Forest plots for the meta-analyses comparing the combined therapy with leflunomide and CS versus control group of CS alone on the CR and overall response of proteinuria in patients with IgAN; A, forest plots for the incidence of CR of proteinuria; and B, forest plots for the overall response.

Figure 3.

Forest plots for the meta-analyses comparing the combined therapy with leflunomide and CS versus control group of CS alone on UPE in patients with IgAN.

Figure 4.

Forest plots for the meta-analyses comparing the combined therapy with leflunomide and CS versus control group of CS alone on renal function in patients with IgAN; (A) forest plots for the changes of SCr; and (B) forest plots for the changes of eGFR.

Figure 5.

Forest plots for the meta-analyses comparing the incidence of adverse events between patients treated with a combined therapy and CS alone; (A) incidence of any GI discomfort; (B) incidence of elevated ALT/AST; (C) incidence of infection; (D) incidence of elevated glucose that required medical treatment; and (E) incidence of elevated BP that required medical treatment.

Figure 6.

Funnel plot for the evaluation of publication biases of the meta-analyses; (A) CR of proteinuria; (B) overall response; (C) changes of UPE; (D) changes of SCr; (E) changes of eGFR; F) incidence of any GI discomfort; (G) incidence of elevated ALT/AST; and (H) incidence of infection. The full search strategy for PubMed. (‘IgA nephropathy’ OR ‘immunoglobulin A nephropathy’ OR ‘IgA nephritis’ OR ‘IgA glomerulonephritis’ OR ‘Berger's disease’ OR ‘IgAN’) AND (leflunomide) AND (random OR randomly OR randomized OR randomized OR placebo OR controlled).