Background/Purpose: Lupus nephritis (LN) is seen in approximately 40–60 % of patients with systemic lupus erythematosus (SLE) and contributes significantly to morbidity and mortality in this population. The definitive diagnosis is made with a kidney biopsy, and disease severity is classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) system, which guides management. The approach to active class III and IV LN involves glucocorticoids and mycophenolate mofetil (MMF), with the addition of calcineurin inhibitors (CNIs) based on patient characteristics. CNIs exert potent immunosuppressive effects by blocking T-lymphocyte activation and inhibiting the production of interleukin-2 and have traditionally been used as immunosuppression in renal transplantation. Through this meta-analysis, we aim to compare the use of the CNIs tacrolimus (TAC) and Voclosporin (VOC) in active LN.

Methods: A comprehensive review of PubMed, Scopus, and the Cochrane Library was performed to locate relevant clinical trials. Five randomized controlled trials (n = 1 311) met inclusion criteria. Three trials compared TAC with conventional induction regimens (cyclophosphamide or MMF; n = 777). Two placebo-controlled trials evaluated VOC on an MMF/low-dose-steroid background (n = 534). Pooled risk ratios (RRs) were determined using Mantel–Haenszel common-effect and random-effects models. Heterogeneity among studies was evaluated with I² and τ² metrics. An indirect Bucher comparison was conducted to analyze differences between TAC and VOC. A p-value < 0.05 was considered statistically significant.

Results: We evaluated five studies in total with the network meta-analysis framework. TAC was associated with a significant increase in complete/partial renal response (RR = 1.41; 95 % CI 1.20–1.66; p < 0.0001), although substantial heterogeneity was present (I² = 72.8 %, τ² = 0.054). A random-effects synthesis attenuated the estimate (RR = 1.36; 95 % CI 1.00–1.86; p = 0.048). VOC significantly improved renal response (common-effect RR = 1.78; 95 % CI 1.35–2.34; p < 0.0001) with no observed between-study heterogeneity (I² = 0 %). An indirect Bucher comparison of pooled random-effects estimates showed no statistically significant difference between TAC and VOC (log RR = –0.23; SE = 0.164); the corresponding RR was 0.79 (95 % CI 0.58–1.09).

Conclusion: Based on this meta-analysis, both calcineurin inhibitors improve short-term renal response in active lupus nephritis when added to standard care. Voclosporin shows a larger and more consistent benefit across trials (RR 1.78), whereas tacrolimus exhibits greater between-study variability. Nevertheless, the indirect Bucher comparison does not establish the clear superiority of either drug. These findings highlight the need for additional studies that directly compare calcineurin inhibitors, with particular emphasis on their relative efficacy, safety, and patient adherence.

Forest plot for Tacrolimus trials

Forest plot Voclosporin trials

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tacrolimus-versus-voclosporin-for-active-lupus-nephritis-a-comparative-meta-analysis-of-renal-response/