Background We previously reported successful use of multi-target therapy using tacrolimus (TAC), mizoribine (MZR), and prednisolone for systemic lupus erythematosus. More data is needed to confirm usefulness of this combination therapy for severe disease forms such as lupus nephritis.
Objectives To examine efficacy and safety of multi-target therapy for lupus nephritis.
Methods Retrospective review of electric medical record was performed for all the 28 patients who received multi-target usingTAC, MZR and corticosteroids for induction or maintenance of lupus nephritis at St. Luke's International Hospital, Tokyo, Japan. For efficacy analysis, we extracted a series of change in serum creatinine, serum complement level, urine protein creatinine ratio (UPCR), dose of corticosteroid. Patients with induction therapy were separately analyzed from those with maintenance therapy. We further reviewed safety profile such as adverse events occurred during the use of multi-target therapy, drug survival rate, or reasons for discontinue multi-target therapy in all patients. Complete remission of lupus nephritis was defined as a value of proteinuria <0.4 g/gCr, normal urinary sediment, serum albumin 3.5 g/dl and a normal value of serum creatinine. Partial remission was defined as an at least 50 per cent improvement in proteinuria and haematuria, serum albumin 3.0 g/dl and a normal value of serum creatinine or no more than 15 per cent above baseline values.
Results Fourteen patients (mean aged 36.4 years) were given multi-target therapy as induction therapy, while the other 14 patient (mean aged 34.9 years) were given as maintenance therapy. As for induction patients, their mean baseline parameters were as follows: UPCR 4.34 g/gCr, serum creatinine 0.74mg/dl, C3 47.4mg/dl, and C4 7.1mg/dl. Within 6 month, 13 out of 14 induction patients achieved remission. Their mean doses of prednisolone at baseline, 3 months, and at 6 months are 59.4mg/day, 12.3mg/day, and 8.1mg/day, respectively. In maintenance patients, mean doses of prednisolone at baseline and at 6 months were 16.6mg/day and 8.1mg/day, respectively. There was one disease flare within 12 months. There was one disease flare during induction therapy and 3 flares during maintenance therapy. There was one case of serious adverse event which required hospitalization due to pyelonephritis during induction therapy.
Conclusions This study demonstrated efficacy and safety of multi-target therapy with TAC and MZR for induction and maintenance of lupus nephritis.
Nomura A, Shimizu H, Kishimoto M, et al. Efficacy and safety of multitarget therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis. Lupus. 2012 Nov;21(13):1444-9. doi: 10.1177/0961203312458468.
Disclosure of Interest None declared