Effectiveness of tacrolimus in patients with lupus nephritis: A randomized controlled trials meta-analysis

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of tacrolimus in the treatment of lupus nephritis (LN) by synthesizing data from randomized controlled trials (RCTs). MATERIALS AND METHODS: A comprehensive search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science for RCTs involving tacrolimus in patients with LN, published up to October 31, 2024. Eligible studies compared tacrolimus-either as monotherapy or in combination with agents such as prednisolone or mycophenolate mofetil (MMF) to control treatments like placebo or cyclophosphamide. Two reviewers independently screened the studies, extracted data, and assessed methodological quality. Statistical analyses were performed using Review Manager 5.3 and Stata 15. Standardized mean differences (SMDs) were used for continuous outcomes, and relative risks (RRs) for dichotomous outcomes. RESULTS: Of the 484 records screened, 9 RCTs involving 1,187 patients met the inclusion criteria. Tacrolimus significantly reduced urine protein compared to MMF, placebo, and intravenous cyclophosphamide (SMD: -0.33, 95% CI: -0.48, -0.19, p < 0.0001). It also led to modest improvements in serum creatinine (SMD: 0.17, 95% CI: 0.03, 0.30, p = 0.01) and serum albumin (SMD: 0.19, 95% CI: 0.06, 0.31, p = 0.005). However, no significant differences were observed in SLE Disease Activity Index, proteinuria, or serum C3 levels (p > 0.05). Tacrolimus was associated with a slightly lower risk of adverse events, although the differences was not statistically significant (RR: 0.96, 95% CI: 0.86 - 1.07, p = 0.46). Sensitivity analyses indicated some instability in the results for urine protein and serum creatinine. CONCLUSION: Tacrolimus appears effective in improving select renal biomarkers in patients with LN, particularly in reducing urine protein and improving serum creatinine and serum albumin levels. However, it showed no significant benefit in other clinical disease activity markers when compared to standard therapies. Although associated with a sightly lower incidence of adverse events, the overall quality of evidence was moderate to low. Further high-quality studies are warranted to confirm these findings.