A Meta-Analysis of Randomized Controlled Trials Comparing Tacrolimus with Intravenous Cyclophosphamide in the Induction Treatment for Lupus Nephritis

A Meta-Analysis of Randomized Controlled Trials Comparing Tacrolimus with Intravenous Cyclophosphamide in the Induction Treatment for Lupus Nephritis

JIN DENG,¹ DONGMEI HUO,² QIAOYUAN WU,² ZHENHUA YANG² and YUNHUA LIAO²

¹Department of Nephrology, The First Affiliated Hospital of Nanhua University, Hengyang, P.R. China
²Department of Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China

Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). As a standard treatment regimen for remission induction of proliferative LN, intravenous cyclophosphamide (IVCYC) and corticosteroids has been widely accepted. However, cyclophosphamide (CYC) is associated with significant adverse effects. Tacrolimus, a T-cell-specific calcineurin inhibitor, shares similar immunosuppressive actions with cyclosporine. We performed a meta-analysis of randomized controlled trials (RCTs) to compare efficacy and safety between tacrolimus (oral administration and/or IV injection) and IVCYC in the induction treatment for LN. We identified 5 trials, including 225 patients. Meta-analysis showed that tacrolimus could significantly increase complete remission (RR 1.61, 95% CI, 1.17 to 2.23; P = 0.004), response rate (RR 1.25, 95% CI, 1.09 to 1.44; P = 0.001), serum albumin level (SMD 1.11, 95% CI, 0.17 to 2.06; P = 0.02) and anti-dsDNA negative conversion rate (RR 1.34, 95% CI, 1.01 to 1.78; P = 0.04), and decrease urine protein (SMD −0.52, 95% CI, −0.83 to −0.22; P = 0.0008), systemic lupus erythematosus disease activity index (SLE-DAI) (SMD −0.59, 95% CI, −1.00 to −0.19; P = 0.004) compared with that of IVCYC. The rates of gastrointestinal symptoms and irregular menstruation (or amenorrhea) were significantly lower in tacrolimus group than IVCYC group (RR 0.46, 95% CI, 0.22 to 0.93; P = 0.03 and RR 0.14, 95% CI, 0.04 to 0.50; P = 0.003). In conclusion, tacrolimus was found to be more effective and safer than IVCYC as an induction therapy for Chinese LN patients.

keywords —— cyclophosphamide; lupus nephritis; meta-analysis; systematic review; tacrolimus

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Tohoku J. Exp. Med., 2012, 227, 281-288

Correspondence: Yunhua Liao, Department of Nephrology, the First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, P.R. China.

e-mail: yunhualiao1008@yahoo.com.cn