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Investigation on the benefits of mycophenolate mofetil and therapeutic drug monitoring in the treatment of Japanese patients with lupus nephritis

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Abstract

Background

Mycophenolate mofetil (MMF) is recommended as a first-line immunosuppressant to treat lupus nephritis (LN). Prognosis and therapeutic response in LN are known to vary depending on race. We investigated the benefits of MMF and therapeutic drug monitoring (TDM) in the treatment of Japanese LN patients.

Methods

In this retrospective cohort study, a total of 20 patients with LN who started MMF treatment were included. Clinical data were collected regularly after MMF administration. We evaluated complete remission (CR) rate as the primary outcome. Predictors of CR were identified using univariate and multivariate analyses. In the research of TDM, the correlation with the area under the curve (AUC) was analyzed at MMF dose, single-point value, treatment response, and adverse events.

Results

Overall, 70% of cases showed CR; both flare-ups and refractory cases had favorable results. Cases of LN with nephrotic syndrome (NS) or class III/IV + V showed a significantly lower CR rate (p < 0.005). The ratio of maintaining CR after MMF therapy was as high as 85.7%. In multivariate analysis, NS was an independent negative predictor of CR (HR 0.09, 95% confidence interval 0.01–0.81; p = 0.03). The relationship between AUC and MMF dose was low, and AUC correlated with trough level (r = 0.73). AUC tended to be high in the treatment responder (p = 0.09), but did not correlate with adverse events of infection (p = 0.92).

Conclusion

MMF is a beneficial treatment option for Japanese LN patients, and further investigation on TDM-based therapy is needed.

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Acknowledgements

This study was supported partly by a Grant-in-Aid for Progressive Renal Diseases Research, Research on Rare and Intractable Disease, from the Ministry of Health, Labour and Welfare of Japan. The authors also acknowledge Editage for providing editorial and publication support.

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Authors and Affiliations

  1. Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Takayuki Katsuno, Takaya Ozeki, Asaka Hachiya, Hangsoo Kim, Noritoshi Kato, Takuji Ishimoto, Sawako Kato, Tomoki Kosugi, Naotake Tsuboi, Masashi Mizuno & Shoichi Maruyama

  2. Department of Internal Medicine, Eijinkai Sato Hospital, Konan, Japan

    Takenori Ozaki

  3. Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan

    Takayuki Katsuno & Yasuhiko Ito

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  1. Takayuki Katsuno
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  2. Takenori Ozaki
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  3. Takaya Ozeki
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  13. Shoichi Maruyama
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Corresponding author

Correspondence to Takayuki Katsuno.

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Conflict of interest

The Department of Nephrology, Nagoya University Graduate School of Medicine received research promotion grants from Otsuka Pharmaceutical Co, Kissei Pharmaceutical Co, Novartis Pharma K.K, Kowa Pharmaceutical Co, Chugai Pharmaceutical Co, Nippon Boehringer Ingelheim Co ., Ltd, Pfizer Japan Inc, Kyowa Hakko Kirin Co ., Ltd, Torii Pharmaceutical Co.,Ltd, Astellas Pharma Inc, MSD K.K, Daiichi Sankyo Company Limited, Takeda Pharmaceutical Company Limited, Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd, Teijin Pharma Limited, and Mochida Pharmaceutical Co ., Ltd.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee at which the studies were conducted (IRB Approval Number 2017-0086) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

The ethical committee approved this retrospective cohort study without written informed consent, but informed consent was obtained from most patients at the time of renal biopsy.

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Katsuno, T., Ozaki, T., Ozeki, T. et al. Investigation on the benefits of mycophenolate mofetil and therapeutic drug monitoring in the treatment of Japanese patients with lupus nephritis. Clin Exp Nephrol 22, 1341–1350 (2018). https://doi.org/10.1007/s10157-018-1590-2

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  • DOI: https://doi.org/10.1007/s10157-018-1590-2

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