Dataset Information

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.

SUBMITTER: Lv G

PROVIDER: S-EPMC9262374 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCorticosteroids or immunosuppressants and supportive treatment in reducing the risk of proteinuria and end-stage kidney disease (ESKD) in immunoglobulin A (IgA) nephropathy (IgAN) patients were still controversial. The purpose of this meta-analysis was to evaluate the efficacy and safety of immunosuppressants or corticosteroids compared with supportive therapy for treatment of IgAN in order to provide guidance for clinical practice.MethodsWe conducted an online search in PubMed, Embase, Cochrane Library, and Web of Science databases to collect randomized control trials (RCTs) about the efficacy and safety of immunosuppressants or corticosteroids compared with supportive therapy for treatment of IgA for relevant literature published from the databases' inception to August 21, 2021. The Cochrane risk assessment tool was used to assess the risk of bias in the included studies and analyzed by Revman 5.4 software, and Stata 15.0 statistical software was adopted for meta-analysis.ResultsA total of 10,622 related studies were retrieved, and 11 RCTs were finally included in the meta-analysis, with a total sample size of 809 cases. The primary outcome measures for immunosuppressants or corticosteroids were better than those for supportive therapy: proteinuria [weighted mean difference (WMD) =-0.54, 95% confidence interval (CI): -0.63, -0.44, Z =10.79, P<0.001] and ESKD [relative risk (RR) =0.189, 95% CI: 0.059, 0.605, Z =2.81, P=0.005]. The secondary outcome measures were also better than that for supportive treatment: glomerular filtration rate [standardized mean difference (SMD) =0.32, 95% CI: 0.09, 0.54, Z =2.48, P=0.013]. The incidence of adverse reactions was consistent with that of supportive treatment, and the difference was not statistically significant (RR =1.06, 95% CI: 0.71, 1.59, Z =0.28, P=0.777).DiscussionCurrent evidence shows that immunosuppressants and corticosteroids can significantly reduce the risk of proteinuria and ESKD in IgAN patients. Due to limited quality and quantity of the included studies, more high-quality studies are need to verify above conclusion. In addition, we hope that more rationally designed multicenter RCTs that are not limited to short-term treatment outcomes will be conducted in the future.

Project description:Background: The efficacy and safety of immunosuppressive monotherapy agents were evaluated for immunoglobulin A nephropathy (IgAN) using a network meta-analysis approach. Methods: Randomized controlled trials (RCTs) published prior to October 1, 2019, using immunosuppressive agents for treating IgAN, were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science databases. Relative risks (RRs) or standard mean differences with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes were clinical remission, end-stage renal disease (ESRD), and serious adverse events (SAEs). The secondary outcomes were urinary protein excretion and serum creatinine. Results: Twenty-five RCTs with 2,005 participants were deemed eligible. Six medications were evaluated: corticosteroids, mycophenolate mofetil (MMF), tacrolimus (TAC), cyclosporine, leflunomide, and hydroxychloroquine (HCQ). Steroids (RR 1.50, 95% CI 1.17-1.93), MMF (RR 2.05, 95% CI 1.15-3.65), TAC (RR 3.67, 95% CI 1.06-12.63), and HCQ (RR 3.25, 95% CI 1.05-10.09) significantly improved clinical remission rates compared to supportive care alone. Only steroids reduced the risk of ESRD (RR 0.35, 95% CI 0.12-0.98); however, there were significantly more SAEs than in the control group (RR 2.90, 95% CI 1.37-6.13). No significantly different effects in serum creatinine levels were found among the therapies. MMF showed no significant improvement in remission when excluding studies with a follow-up of fewer than 2 years in the sensitivity analysis (RR 1.41, 95% CI 0.40-4.92). The effect of TAC in the decrease of proteinuria was reversed after discontinuing medication for 3 months; the long-term effects of HCQ could not be evaluated due to the short follow-up duration. Conclusion: Corticosteroids might induce remission and increase renal survival in IgAN; however, adverse reactions should be taken into consideration. MMF, TAC, and HCQ might improve the remission of proteinuria when treating IgAN, but showed no superiority compared to steroids, and the long-term effects require further study.