Systematic Review and Network Meta-Analysis of Initial Treatments for Lupus Nephritis

Abstract

Introduction: This study aimed to evaluate the comparative efficacy and safety of various initial treatments for active lupus nephritis (LN) through a systematic review and network meta-analysis (NMA). Methods: We conducted a comprehensive literature search across multiple databases from inception to February 2025 to identify randomized controlled trials (RCTs) comparing initial treatments for LN. We performed a frequentist random-effects NMA using the restricted maximum likelihood method to estimate heterogeneity. We used the GRADE approach to assess the certainty of evidence. Results: We included 40 RCTs encompassing 5450 patients and 16 interventions (12 drugs administered alone or in combination). Mycophenolic acid analogs (MPAAs) were selected as the common comparator. The network meta-analysis revealed that voclosporin (VCS) combined with MPAA (risk difference [RD]: 281.38 more/1000, 95% confidence interval [CI]: 146.26 more to 456.42 more; high certainty), belimumab (BEL) combined with MPAA (RD: 145.02 more/1000, 95% CI: 72.73 more to 230.92 more; high certainty), and obinutuzumab (OBI) combined with MPAA (RD: 134.23 more/1000, 95% CI: 30.37 more to 269.68 more; moderate certainty) increased complete renal response (CRR) compared with MPAA alone. Tacrolimus (TAC) combined with MPAA (RD: 113.69 more/1000, 95% CI: 25.23 more to 217.7 more; low certainty) also showed potential benefits but with low certainty evidence. Conclusion: Combination therapies, particularly VCS, BEL, or OBI with MPAA, provide enhanced outcomes for LN initial treatment. Given the complexity of LN, clinicians should weigh these findings alongside considerations such as drug availability, cost, and individual patient preferences to guide treatment decisions.

Introduction: This study aimed to evaluate the comparative efficacy and safety of various initial treatments for active lupus nephritis (LN) through a systematic review and network meta-analysis (NMA). Methods: We conducted a comprehensive literature search across multiple databases from inception to February 2025 to identify randomized controlled trials (RCTs) comparing initial treatments for LN. We performed a frequentist random-effects NMA using the restricted maximum likelihood method to estimate heterogeneity. We used the GRADE approach to assess the certainty of evidence. Results: We included 40 RCTs encompassing 5450 patients and 16 interventions (12 drugs administered alone or in combination). Mycophenolic acid analogs (MPAAs) were selected as the common comparator. The network meta-analysis revealed that voclosporin (VCS) combined with MPAA (risk difference [RD]: 281.38 more/1000, 95% confidence interval [CI]: 146.26 more to 456.42 more; high certainty), belimumab (BEL) combined with MPAA (RD: 145.02 more/1000, 95% CI: 72.73 more to 230.92 more; high certainty), and obinutuzumab (OBI) combined with MPAA (RD: 134.23 more/1000, 95% CI: 30.37 more to 269.68 more; moderate certainty) increased complete renal response (CRR) compared with MPAA alone. Tacrolimus (TAC) combined with MPAA (RD: 113.69 more/1000, 95% CI: 25.23 more to 217.7 more; low certainty) also showed potential benefits but with low certainty evidence. Conclusion: Combination therapies, particularly VCS, BEL, or OBI with MPAA, provide enhanced outcomes for LN initial treatment. Given the complexity of LN, clinicians should weigh these findings alongside considerations such as drug availability, cost, and individual patient preferences to guide treatment decisions.