A meta-analysis of randomized controlled trials comparing tacrolimus with intravenous cyclophosphamide in the induction treatment for lupus nephritis

Tohoku J Exp Med. 2012 Aug;227(4):281-8. doi: 10.1620/tjem.227.281.

Abstract

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.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Adult
  • Complement C3 / metabolism
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Female
  • Humans
  • Injections, Intravenous
  • Lupus Nephritis / complications
  • Lupus Nephritis / drug therapy*
  • Male
  • Proteinuria / complications
  • Publication Bias
  • Randomized Controlled Trials as Topic*
  • Remission Induction
  • Serum Albumin / metabolism
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Complement C3
  • Serum Albumin
  • Cyclophosphamide
  • Tacrolimus