Efficacy and safety of tacrolimus for induction therapy in patients with active lupus nephritis.

After the completion of a double-blind placebo-controlled trial, tacrolimus (TAC) was approved for the treatment of lupus nephritis (LN) in Japan. However, the approved maximal dose, 3 mg/day, is almost half the dose used for induction therapy outside Japan. In this study, we retrospectively evaluated the efficacy and safety of low-dose TAC (≤3 mg/day) for induction therapy in 13 adult patients (2 men and 11 women) with active LN. Eight patients were treated for LN flares. Twelve patients underwent renal biopsies: 8 with class IV, 2 with class III + V, 1 with class IV + V, and 1 with class V renal histology, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. The mean initial doses of prednisone and TAC were 34.6 ± 14.5 and 2.7 ± 0.6 mg/day, respectively. All the patients achieved a complete remission (CR) at 7.7 ± 6.7 months (mean ± SD) after the last administration of TAC, except for 2 patients who discontinued TAC treatment; 1 because of worsening systemic lupus erythematosus and 1 because of hypertension. Two patients experienced a flare-up after achieving CR. The mean blood TAC concentration 12 h after the last administration (C12) was significantly lower among the patients with flare-ups than among those with a sustained CR (1.5 ± 1.5 vs. 5.1 ± 1.9 ng/mL, P = 0.034). These data showed that low-dose TAC was effective for induction therapy in patients with active LN, although a lower TAC concentration may be associated with a poor outcome.