BACKGROUND: A novel purine synthesis inhibitor, mizoribine (MZR), with a similar activity to that of mycophenolate mofetil, was developed in Japan. We suspected that long-term oral MZR intermittent pulse therapy (MZR-P) might be more effective than the conventional daily MZR regimen due to the higher peak serum MZR levels that are achieved. Here, we examined the clinicopathologic efficacy of MZR-P treatment in 10 young patients with diffuse proliferative lupus nephritis (DPLN), including 3 patients who received MZR-P as their primary cytotoxic therapy. METHODS: After their most recent renal flare-ups, all the patients were treated using MZR-P combined with oral prednisolone (PDN). MZR was administered as a single daily dose of 6-10 mg/kg per day (maximum dose of 500 mg) on 2 days of the week (Monday and Thursday) for at least 12 months or longer. The concomitantly administered PDN dose was gradually reduced. RESULTS: The baseline characteristics of the patients were as follows: mean age 15 years; urinary protein/creatinine (Up/cr) ratio 1.57 +/- 1.05 mg/mg; serum C3 level 50.3 +/- 19.7 mg/dl; serum complement hemolytic activity (CH50) 18.1 +/- 9.9 U/ml; serum anti-dsDNA antibody titer 177.5 +/- 152.7 IU/ml; serum creatinine 0.6 +/- 0.1 mg/dl, and European Consensus Lupus Activity Measurement (ECLAM) index 4.9 +/- 2.6. Despite the gradual tapering of the PDN dose, marked improvements compared with the baseline values were observed at the last observation, mean interval of 29 months after the start of treatment: Up/cr ratio 0.19 +/- 0.14; ECLAM index 1.3 +/- 0.7 (p < 0.01); serum C3 level 76.5 +/- 22.1 mg/dl; serum CH50 value 31.9 +/- 8.7 U/ml, and anti-dsDNA antibody titer 34.2 +/- 20.5 IU/ml (p < 0.05). The serum creatinine level remained within the normal range in all study participants. Post-treatment renal biopsies were performed in 5 of the patients; histology showed a marked attenuation of lesion progression. No serious adverse effects were observed. CONCLUSION: We believe that long-term MZR-P may prove to be a treatment of choice for young patients with DPLN. However, confirmation is needed as this preliminary study is limited by the small number of subjects, lack of controls, and its retrospective nature. Copyright 2008 S. Karger AG, Basel.
BACKGROUND: A novel purine synthesis inhibitor, mizoribine (MZR), with a similar activity to that of mycophenolate mofetil, was developed in Japan. We suspected that long-term oral MZR intermittent pulse therapy (MZR-P) might be more effective than the conventional daily MZR regimen due to the higher peak serum MZR levels that are achieved. Here, we examined the clinicopathologic efficacy of MZR-P treatment in 10 young patients with diffuse proliferative lupus nephritis (DPLN), including 3 patients who received MZR-P as their primary cytotoxic therapy. METHODS: After their most recent renal flare-ups, all the patients were treated using MZR-P combined with oral prednisolone (PDN). MZR was administered as a single daily dose of 6-10 mg/kg per day (maximum dose of 500 mg) on 2 days of the week (Monday and Thursday) for at least 12 months or longer. The concomitantly administered PDN dose was gradually reduced. RESULTS: The baseline characteristics of the patients were as follows: mean age 15 years; urinary protein/creatinine (Up/cr) ratio 1.57 +/- 1.05 mg/mg; serum C3 level 50.3 +/- 19.7 mg/dl; serum complement hemolytic activity (CH50) 18.1 +/- 9.9 U/ml; serum anti-dsDNA antibody titer 177.5 +/- 152.7 IU/ml; serum creatinine 0.6 +/- 0.1 mg/dl, and European Consensus Lupus Activity Measurement (ECLAM) index 4.9 +/- 2.6. Despite the gradual tapering of the PDN dose, marked improvements compared with the baseline values were observed at the last observation, mean interval of 29 months after the start of treatment: Up/cr ratio 0.19 +/- 0.14; ECLAM index 1.3 +/- 0.7 (p < 0.01); serum C3 level 76.5 +/- 22.1 mg/dl; serum CH50 value 31.9 +/- 8.7 U/ml, and anti-dsDNA antibody titer 34.2 +/- 20.5 IU/ml (p < 0.05). The serum creatinine level remained within the normal range in all study participants. Post-treatment renal biopsies were performed in 5 of the patients; histology showed a marked attenuation of lesion progression. No serious adverse effects were observed. CONCLUSION: We believe that long-term MZR-P may prove to be a treatment of choice for young patients with DPLN. However, confirmation is needed as this preliminary study is limited by the small number of subjects, lack of controls, and its retrospective nature. Copyright 2008 S. Karger AG, Basel.