Prospective Randomized Controlled 96-week Study to Evaluate the Efficacy and Safety of Tacrolimus and Glucocorticoid as Continuous Induction-Maintenance Treatment for Class III/IV±V Lupus Nephritis

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Background: Tacrolimus (TAC) and glucocorticoid as continuous induction-maintenance therapy for lupus nephritis (LN) has never been investigated. We conducted a prospective randomized open-label multicenter study to evaluate its efficacy and safety against standard-of-care mycophenolate (MMF) and glucocorticoid dual immunosuppression in Asian patients with active severe LN. Methods: Patients with biopsy-proven Class III/IV±V LN were randomized to receive pulse methylprednisolone (500mg/500mg/150mg) for 3 days followed by oral prednisolone (0.7mg/kg/day, then taper) in combination with either TAC (initial dose 2mg bid; target trough level 6-8ng/mL) or MMF (1g bid), then followed for 96 weeks. Primary endpoint was sustained renal response (SRR) [defined as proteinuria reduced by >50% compared with baseline and 24h urine protein <1g and serum creatinine not higher than 15% above baseline and no disease flare or rescue therapies] at Week 96. Secondary endpoints included complete renal response rates (CR), adverse events, and time-to-renal related adverse events/death. Results: 130 patients were randomized (65 in each group). TAC and MMF treatment groups showed similar rates of SRR (58.5% vs 69.2%, OR 0.62; 95% CI 0.29-1.29; p=0.2) and CR (55.4% vs 63.1%, OR 0.72; p=0.36) at Week 96. SRR rates for TAC and MMF groups were 53.8% vs 52.3% at Week 24, and 63.1% vs 66.2% at Week 48 respectively. Time-to-renal related adverse events/death were similar in both groups (HR 0.70; 95% CI 0.37-1.35; p=0.29). Overall adverse event rates were 69.2% and 70.8% in TAC and MMF groups respectively (p=1.00), while serious adverse events were more frequent in the MMF group (12.3% vs 30.8%, p=0.02). Acute kidney injury (16.9% vs 3.1%) and tremor (16.9% vs 0%) were more frequent in TAC-treated patients, while leucopoenia (1.5% vs 12.3%) was more frequent in the MMF group. Three patients in the MMF group died. Conclusion: Immunosuppressive regimen with TAC combined with glucocorticoid showed comparable efficacy as MMF with glucocorticoid, as induction-maintenance treatment for LN over 96 weeks, with similar overall adverse event rate but a different safety profile. Funding: Private Foundation Support, Clinical Revenue Support

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