Comparative efficacy of intravenous cyclophosphamide, mycophenolate mofetil, and tacrolimus as induction therapy for lupus nephritis: A randomized controlled open-label trial.

Abstract

ObjectiveTo compare the efficacy of cyclophosphamide (IV CYC), mycophenolate mofetil (MMF), and tacrolimus (TAC), as induction treatment for lupus nephritis (LN).MethodsThis randomized, open-label, non-inferiority, active-controlled three-arm study included children and adult patients aged ≥10 years with clinical or biopsy-proven LN over a period of 1 year. Patients were randomized in a 1:1:1 ratio to receive IV CYC (0.5-0.75 g/m² monthly for 6 doses), MMF (2-3 g/day), or TAC (0.08-1 mg/kg/day). The primary outcome was the proportion of patients achieving renal response [complete (CR) or partial (PR)] at week 24 and secondary outcomes included the proportion of CR, PR, change in complements, anti-dsDNA antibody, and 24-hour urine protein levels, SLEDAI-2K and renal-SLEDAI scores from baseline to week 24. Serum CXCL10 was assessed at baseline and follow-up. Intention-to-treat analysis was performed.Results82 patients (94% females; median age 27.5 years) were randomized to receive IV CYC (28), MMF (27), and TAC (27). At 24 weeks, the renal response rates were 53.5%, 66.6%, and 62.9% in IV CYC, MMF, and, TAC groups, respectively. The lower limit of the confidence interval for the difference in renal response at 24 weeks between treatment groups was less than 20% (non-inferiority margin) (p = .58). Serum CXCL10 reduced significantly post-treatment in all three groups (p < .001). Three patients in the IV CYC group and one patient in TAC group died due to serious infections.ConclusionTAC was non-inferior compared to IV CYC and MMF for LN as induction therapy, with a comparable safety profile during the study period.