Mizoribine intermittent pulse protocol for induction therapy for systemic lupus erythematosus in children: an open-label pilot study with five newly diagnosed patients.

The objective of the current work is to report our preliminary experience with the mizoribine (MZR) intermittent pulse protocol for induction therapy for newly diagnosed pediatric-onset systemic lupus erythematosus (SLE). Five consecutive patients who were newly diagnosed as having SLE with biopsy-proven lupus nephritis were recruited for an open-label trial of prednisolone (PDN) and MZR intermittent pulse therapy (10 mg/kg for 2 days of the week for 12 months). Data on the renal response and serologic lupus activity were collected prospectively. The baseline characteristics of the patients were: mean age, 11 years; urinary protein/creatinine ratio (U-prot./cre.), 0.99 +/- 0.91; serum complement hemolytic activity (CH50), 10.6 +/- 1.3 (normal, 23-46 U/ml); serum anti-dsDNA antibody titer, 258.6 +/- 125.5 IU/ml (normal, <12.0 IU/ml); serum creatinine, 0.5 +/- 0.1 mg/dl; European Consensus Lupus Activity Measurement index (ECLAM), 7.4 +/- 1.1. The primary endpoint was the interval until the development of a flare of SLE. Despite gradual tapering of the PDN dose, significant improvement as compared to the baseline values was observed in all the parameters examined at 3, 6, and 12 months of treatment. After 12 months therapy, complete response was achieved in all of the patients, except for 1 patient who showed poor drug compliance. In two patients who had severe lupus nephritis at the first renal biopsy, marked histologic improvement was confirmed at the second renal biopsy. No serious adverse effects were observed. We believe that the MZR pulse protocol combined with PDN for induction therapy may be the treatment of choice in selected young patients with SLE. Further studies to confirm the long-term efficacy and safety of our current protocol in larger numbers of patients are, however, needed.