Background In Japan, a placebo-controlled clinical trial of tacrolimus for lupus nephritis was performed to investigate the efficacy and safety of this agent. Based on the results obtained, administration of tacrolimus at an oral dose of 3 mg/day was approved for the treatment of lupus nephritis.
Objectives The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus (TAC) combination therapy during the maintenance phase of systemic lupus erythematosus (SLE). TAC was added to the existing therapy if the clinical symptoms worsened and/or if there was a decrease in the serum complements titer because it allowed for a decrease in the dose of prednisolone (PSL).
Methods From 2009 to 2012, 38 patients were included in the study period for 1 year. TAC combination therapy (dosage range: 1 mg to 5 mg once daily) was given if there was worsening of any mild manifestations of active SLE, such as arthritis, skin eruptions, or asymptomatic nephritis, and/or if there was a decrease in the serum complement titer (C3c). This study reviewed the SLE Disease Activity Index (SLEDAI) score, the dosage of PSL, the serum levels of C3c, the anti-dsDNA titers and proteinuria.
Results Twenty-eight patients were treated with TAC combination therapy and showed symptom improvement with the following results: 1) the dosage of PSL was reduced from 11.7 ± 5.6 to 8.2 ± 4.2 (mg/day) (P<0.001), 2) the serum C3c concentration increased from 74.7 ± 21.9 to 86.4 ± 17.8 (mg/dl) (P=0.006), 3) the anti-dsDNA titer decreased from 39.6 ± 68.0 to 24.8 ± 49.1 (U/ml) (P<0.001) and 4) the SLEDAI score improved from 6.2 ± 3.7 to 2.6 ± 2.3 (P<0.001). Of note, the components of the SLEDAI with the greatest levels of improvement included headache (decreased from 7 patients to 1 patient), arthritis (from 3 patients to no patients), rash (from 6 patients to 2 patients), alopecia (from 5 patients to no patients), mucosal ulcer (from 2 patients to no patients) and fever (from 5 patients to 1 patient). Although the occurrence of proteinuria decreased from 46.0 ± 95.7 to 30.7 ± 74.2 (mg/dl) upon administration of TAC combination therapy, the difference was not significant (P=0.23). However, 8 patients treated with TAC combination therapy did not show disease improvement nor had worsening SLE. In addition, 2 patients discontinued therapy due to an adverse effect: muscle cramp or rhabdomyolysis. No patients presented abnormal urinalysis, progression to renal failure, or became a candidate for dialysis therapy.
Conclusions TAC combination therapy was clinically useful in the maintenance phase of SLE.
Disclosure of Interest None Declared