Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

Abstract

We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 +/- 31.0% (mean +/- SD) in the tacrolimus group (n = 28) and was increased by 2.3 +/- 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.

Post-marketing surveillance study of the long-term use of mizoribine for the treatment of lupus nephritis: 2-Year results

“…In the present surveillance study, the efficacy of MZR was confirmed based on composite indicators. Numerous reports have been published recently showing that MMF and tacrolimus are effective in terms of providing satisfactory improvements in urine protein [17][18][19]. In the present study, decreases in urine protein levels were also confirmed, and the efficacy of MZR was demonstrated.…”

“…In such cases, decreased renal function, which is one of the ADRs to immunosuppressants, due to long-term treatment is a concern [17,20]. In the present surveillance study, ADRs related to decreased renal function included 1 case of renal impairment and 2 cases of blood creatinine increased.…”

Lupus Nephritis

“…The researchers found that after the treatment, proteinuria was significantly reduced and seven of the nine patients showed a complete clinical response. In a RCT comparing tacrolimus to placebo in 63 patients with LN who had persistent nephritis despite glucocorticoids, tacrolimus was associated with a decrease in LN disease activity index compared with placebo over 28 weeks of treatment (40). In another open-labeled, prospective study of nine patients with diffuse proliferative LN who had persistent proteinuria (.1 g) despite intravenous cyclophosphamide therapy, tacrolimus (0.1 mg/kg per day) was administered for 1 year with target drug levels (4-10 mg/L).…”

The Proton Pump Inhibitor Lansoprazole, but not Rabeprazole, the Increased Blood Concentrations of Calcineurin Inhibitors in Japanese Patients with Connective Tissue Diseases

“…We evaluated the adverse events related to TAC administration (i.e., kidney dysfunction and impaired glucose tolerance) based on the results of an early phase II study of TAC for rheumatoid arthritis and a phase III study of TAC for lupus nephritis (1,2). The criteria for kidney dysfunction during the TAC administration period included either 1) a !…”

“…Calcineurin inhibitors (CNIs) such as tacrolimus (TAC) and cyclosporin A (CSA) are immunosuppressive drugs that inhibit nuclear factor-κB (NF-κB) activity and are used in organ transplantation and to treat connective tissue diseases (CTDs) (1)(2)(3)(4). There are remarkable inter-and intraindividual variabilities in their pharmacokinetics of these nal ulceration.…”