Takayuki Katsuno1,2, Takenori Ozaki3, Takaya Ozeki4, Asaka Hachiya4, Hangsoo Kim4, Noritoshi Kato4, Takuji Ishimoto4, Sawako Kato4, Tomoki Kosugi4, Naotake Tsuboi4, Masashi Mizuno4, Yasuhiko Ito5, Shoichi Maruyama4. 1. Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. katsu11@med.nagoya-u.ac.jp. 2. Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan. katsu11@med.nagoya-u.ac.jp. 3. Department of Internal Medicine, Eijinkai Sato Hospital, Konan, Japan. 4. Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. 5. Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan.
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.
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.
Authors: Mary Anne Dooley; David Jayne; Ellen M Ginzler; David Isenberg; Nancy J Olsen; David Wofsy; Frank Eitner; Gerald B Appel; Gabriel Contreras; Laura Lisk; Neil Solomons Journal: N Engl J Med Date: 2011-11-17 Impact factor: 91.245
Authors: Gerald B Appel; Gabriel Contreras; Mary Anne Dooley; Ellen M Ginzler; David Isenberg; David Jayne; Lei-Shi Li; Eduardo Mysler; Jorge Sánchez-Guerrero; Neil Solomons; David Wofsy Journal: J Am Soc Nephrol Date: 2009-04-15 Impact factor: 10.121
Authors: Frédéric A Houssiau; David D'Cruz; Shirish Sangle; Philippe Remy; Carlos Vasconcelos; Radmila Petrovic; Christoph Fiehn; Enrique de Ramon Garrido; Inge-Magrethe Gilboe; Maria Tektonidou; Daniel Blockmans; Isabelle Ravelingien; Véronique le Guern; Geneviève Depresseux; Loïc Guillevin; Ricard Cervera Journal: Ann Rheum Dis Date: 2010-09-10 Impact factor: 19.103