H Tanaka1, E Oki, K Tsuruga, T Yashiro, I Hanada, E Ito. 1. Department of Pediatrics, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. hirotana@cc.hirosaki-u.ac.jp
Abstract
AIMS: Studies on immunosuppressive treatment with tacrolimus (Tac) in subjects with lupus nephritis (LN) are limited. Here, we report our experience with Tac administered daily as a single-dose for maintenance therapy in young patients with pediatric-onset, long-standing LN. METHODS:Eleven consecutive patients with long-standing biopsy-proven LN were recruited for at least 6 months or longer (6 - 24 months) as part of an open-label trial for the single-daily-dose administration of Tac (3 mg/day, 0.04 - 0.075 mg/kg) without dose increases of concomitantly administered prednisolone (PDN). Tac treatment was started at the time of the most recent flare. Data on clinical parameters and serologic lupus activity were collected prospectively. RESULTS: The baseline characteristics of the patients were as follows: mean age, 18 years; urinary protein/creatinine ratio (Up/cr), 0.74 +/- 1.49; serum C3 level, 69.5 +/- 26.5 mg/dl (normal 79 - 152 mg/dl); serum complement hemolytic activity (CH50), 23.0 +/- 8.9 U/ml (normal 23 - 46 U/ml); serum anti-dsDNA antibody titer, 58.9 +/- 54.2 IU/ml (normal < 12.0 IU/ml); serum creatinine, 0.54 +/- 0.13 mg/dl; and European Consensus Lupus Activity Measurement (ECLAM) index, 4.4 +/- 2.2. Despite the gradual tapering of the PDN dose, a marked improvement, compared with the baseline values was observed in the ECLAM index even at 1 month and in the serological parameters at 3 months after the start of treatment. These favorable results persisted until the end of the study. The Up/cre ratio gradually decreased and had dropped significantly at 24 months after the start of treatment. After a mean of 18 months of treatment, complete responses were achieved in 8 patients (73%) and a partial response was achieved in 2 patients. The remaining one patient showed no response. No serious adverse effects were observed. CONCLUSION: These data suggest that low-dose Tac treatment, administered once daily, is an effective and safe method for managing selected young patients with pediatric-onset, long-standing LN. However, further studies involving a larger number of patients are needed to confirm these results.
RCT Entities:
AIMS: Studies on immunosuppressive treatment with tacrolimus (Tac) in subjects with lupus nephritis (LN) are limited. Here, we report our experience with Tac administered daily as a single-dose for maintenance therapy in young patients with pediatric-onset, long-standing LN. METHODS: Eleven consecutive patients with long-standing biopsy-proven LN were recruited for at least 6 months or longer (6 - 24 months) as part of an open-label trial for the single-daily-dose administration of Tac (3 mg/day, 0.04 - 0.075 mg/kg) without dose increases of concomitantly administered prednisolone (PDN). Tac treatment was started at the time of the most recent flare. Data on clinical parameters and serologic lupus activity were collected prospectively. RESULTS: The baseline characteristics of the patients were as follows: mean age, 18 years; urinary protein/creatinine ratio (Up/cr), 0.74 +/- 1.49; serum C3 level, 69.5 +/- 26.5 mg/dl (normal 79 - 152 mg/dl); serum complement hemolytic activity (CH50), 23.0 +/- 8.9 U/ml (normal 23 - 46 U/ml); serum anti-dsDNA antibody titer, 58.9 +/- 54.2 IU/ml (normal < 12.0 IU/ml); serum creatinine, 0.54 +/- 0.13 mg/dl; and European Consensus Lupus Activity Measurement (ECLAM) index, 4.4 +/- 2.2. Despite the gradual tapering of the PDN dose, a marked improvement, compared with the baseline values was observed in the ECLAM index even at 1 month and in the serological parameters at 3 months after the start of treatment. These favorable results persisted until the end of the study. The Up/cre ratio gradually decreased and had dropped significantly at 24 months after the start of treatment. After a mean of 18 months of treatment, complete responses were achieved in 8 patients (73%) and a partial response was achieved in 2 patients. The remaining one patient showed no response. No serious adverse effects were observed. CONCLUSION: These data suggest that low-dose Tac treatment, administered once daily, is an effective and safe method for managing selected young patients with pediatric-onset, long-standing LN. However, further studies involving a larger number of patients are needed to confirm these results.