Background Tacrolimus (TAC) is an immunosuppressive macrolide that blocks T cell activation by specifically inhibiting calcineurin, and it is widely administered following organ transplantation. Recently some randomized studies have shown that TAC is an effective maintenance treatment for lupus nephritis (LN)(1-2), and TAC has been approved in Japan and some Asian countries for LN. However, the safety and efficacy including the long-term outcome of TAC for LN patients in the real clinical setting may not be clear enough.

Objectives To assess the safety and efficacy including long-term outcome of TAC for LN patients in the real clinical setting, post-marketing surveillance was conducted.

Methods Patients were registered centrally in an all-patient investigation system between 2007 and 2010 from 296 medical sites. The registered patients will be followed for 10 years, and the safety and efficacy were evaluated at weeks 4, 8, 12 and 28,1 year and every year thereafter.

Results This interim analysis included all the registered 1375 patients, and the median follow-up period was 28.7 months (Range:0.1 - 62.6 months). The most common serious adverse drug events were infections, in which herpes zoster, bacterial pneumonia and cellulitis were observed most frequently, at the incident rates of 0.7%, 0.6% and 0.5%, respectively. The spot urine protein : creatinine ratio (P/C ratio) was significantly decreased from four weeks after the TAC treatment (Mean value : 1.7 at baseline to 1.1 at four weeks, p<0.001 and 0.7 at two years, p<0.001). Also, the serum complement C3 and anti-ds DNA antibodies were significantly improved from four weeks after treatment (Mean value, complement C3 : 68mg/dL at baseline to 73mg/dL at four weeks, p<0.001 and 81mg/dL at two years, p<0.001, anti-ds DNA antibodies : 42IU/mL at baseline to 29IU/mL at four weeks, p<0.001 and 20IU/mL at two years, p<0.001).

Conclusions TAC is well tolerated and effective in Japanese patients with LN in the real clinical setting.

References

1. N.Miyasaka, S. Kawai, H.Hashimoto. Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study. Mod Rheumatol. 2009;19:606-615

2. W Chen, Q Liu, W Chen, et al. Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial. Lupus 2012;21(9):944-952

Acknowledgements The authors wish to thank all investigators for their contributions to the implementation of this study.

Disclosure of Interest T. Takeuchi Grant/research support from: Astellas Pharma Inc., N. Wakasugi Employee of: Astellas Pharma Inc., H. Makino Grant/research support from: Astellas Pharma Inc.