Comparative Efficacy of Voclosporin in Combination With Mycophenolate Mofetil Versus Other Treatments in Active Lupus Nephritis: Systematic Review and Network Meta-Analysis

OBJECTIVES: The objective is to determine the comparative effectiveness of voclosporin in combination with mycophenolate mofetil (VCS+MMF) vs current therapies for achieving complete renal response (CR) in patients with active lupus nephritis (LN).

METHODS: A systematic literature review was performed to identify randomized controlled trials (RCTs) for treatments used in active LN. In a Bayesian framework, evidence was synthesized via a network meta-analysis (NMA) using a logistic regression model and logit link function for the outcome of CR. Odds ratios (ORs) with 95% credible intervals (CrIs) were estimated using random effects models to account for observed heterogeneity between included RCTs. Treatment ranking was calculated using the surface under the cumulative ranking curve (SUCRA). Scenario analyses were conducted at 6 and 12 months.

RESULTS: 41 RCTs met the inclusion criteria and 20 were included in the NMA following the feasibility assessment. ORs for CR favored VCS+MMF and belimumab when compared against the network reference of MMF (ORs were, 2.67; [95% CrI: 1.73-4.15] and 1.75; [95% CrI: 1.05-2.95]). Statistical significance was not reached for other calcineurin inhibitors including tacrolimus, both monotherapy (OR, 0.81; 95% CrI: 0.49-1.33) and in combination with MMF (OR, 1.10; 95% CrI: 0.51-2.37), and ciclosporin (OR, 1.35; 95% CrI: 0.24-9.04).

CONCLUSIONS: This analysis suggests that VCS+MMF was ranked the highest (SUCRA: 96%) for achieving CR in active LN compared to other therapies identified in this SLR. This NMA highlights the challenges faced when performing comparative analysis in LN, including: imbalances in potential treatment effect modifiers, heterogenous outcome definitions and follow-up, and quality of evidence (e.g., small sample size). Therefore, results from NMAs in LN should be interpreted with caution.