Use of Tacrolimus and Voclosporin as Induction Therapy in Lupus Nephritis: A Focused Systematic Review and Meta-Analysis of Randomized Evidence

Background: Lupus nephritis (LN) remains a major cause of morbidity among patients with systemic lupus erythematosus, and treatment resistance continues to pose clinical challenges. Calcineurin inhibitors (CNIs), including tacrolimus (TAC) and voclosporin (VCS), are used in induction regimens, but randomized evidence for the two agents arises from clinically different trial designs. This systematic review and meta-analysis separately quantifies randomized evidence for TAC-based and VCS-based induction regimens. Methods: Following PRISMA guidance, the literature search was updated to September 2026. Eligible studies were randomized controlled trials enrolling adults with biopsy-proven active class III, IV, or V LN and were required to report complete and/or partial renal-response data in a form permitting extraction or calculation of an effect estimate. Study inclusion was not based on whether the treatment effect was favorable or statistically significant. Complete renal response was the prespecified primary outcome for quantitative synthesis. Separate random-effects meta-analyses were performed for TAC-based and VCS-based regimens. Because the two evidence sets did not share a sufficiently comparable common comparator, no formal TAC-versus-VCS Bucher comparison was retained. Results: Five randomized controlled trials were included in the quantitative synthesis: three TAC trials and two VCS trials. TAC-based regimens increased complete renal response relative to their respective comparators (RR, 1.36; 95% CI, 1.00–1.86), although heterogeneity was substantial (I2 = 73%) and sensitivity analyses showed that the pooled result was influenced by the multitarget TAC + MMF trial. VCS added to MMF and low-dose glucocorticoids increased complete renal response versus the placebo with the same background therapy (RR, 1.78; 95% CI, 1.35–2.34; I2 = 0%). Safety outcomes were summarized descriptively because definitions and reporting differed across trials. Conclusions: TAC-based and VCS-based induction regimens each showed benefits within their respective randomized trial settings. Differences in background therapy, comparators, study populations, and outcome definitions preclude a reliable indirect efficacy comparison between TAC and VCS. Head-to-head randomized trials using standardized background therapy and outcomes are needed.