Abstract:

Objective: To prospectively observe the clinical efficacy and safety of Corticosteroids in combination with mycophenolate mofetil dispersible tablets (Cicopin○R,MMF, Hangzhou Zhongmei Huadong pharmaceutical Co, Ltd) and tacrolimus (FK506, Hangzhou Zhongmei Huadong pharmaceutical Co, Ltd) (multi-target group) in the induction treatment for lupus nephritis (LN).  Methodology: Seventy-nine patients with biopsy confirmed class IV, V + IV and V + III LN were randomly assigned to either multi-target group (n= 45, 39 females, 6 males, mean age 25.1±9.3 years) or intravenous cyclophosphamide pulse therapy(IV-CYC)(n = 34, 30 females, 4 males, mean age 30.4 ± 8.9 years). All patients received intravenous methylprednisolone pulse therapy followed by oral prednisone. In multi-target group, the dose of MMF and FK506 was adjusted based on the blood level with the MPA-AUC0 ~ 12h level of 20-30 mg • h /L and FK506 trough level 4-7ng/ml. In IV-CYC group, CYC was given in a dose 0.5-0.75g/m2BSA monthly. The induction period was 6months or 9 months according the responses to the therapy. Primary efficacy parameter was complete remission rate (defined as urine protein <0.4g/24h, serum albumin ≥ 35g/l, normal serum creatinine and no extra-renal activity), the secondary parameters were partial remission rate (defined as urinary protein than the base value reduced by 50% or more, and urine protein <3.5g/24h, serum albumin ≥ 30g/l, serum creatinine stable) and incidence of adverse reactions. The clinical efficacy and adverse events were compared between two groups.  Results: The baseline clinical and histological classes had no siginificant differences between multi-target group and IV-CYC group. The accumulated complete remission rate of multi-target group was significantly higher than IV-CYC group (P <0.05) during the induction period. At 6months and 9 months, the complete remission rate was 53.3% and 62.2% respectively in the multi-target group, and 29.4% and 42.6%, in IV-CYC group respectively. Also, Multi-target therapy showed much higher complete remission rate  than IV-CYC therapy for class V+IV (50.0% vs 16.7%, P<0.05) and class V + III(54.5% vs 22.2 %, P> 0.05). In class IV LN, no difference of the remission rate was found between the two groups. The incidence of adverse events in the multi-target group was much lower than that in the IV-CYC group (31.1% vs 70.6%, P <0.01), the major adverse events were new-onset hypertension (11.1%) and herpes zoster (6.7%) in the multi-target group, gastrointestinal reactions (23.5%), leukopenia (13.7%) and skin infections (8.8%) in the IV-CYC group. Three patients( 2 in multi-target group and 1 in IV-CYC group) complicated with pulmonary infection, none died.  Conclusion: The multi-target therapy, which is composed of corticosteroids with Cicopin and tacrolimus, showed more effective than intravenous CYC pulse therapy in inducing remission of lupus nephritis, especially class V+IV, and had a more favorable safety. Howere, multi-center clinical trials are encouraged to evaluate the clinical efficacy and the impact on long-term survival for lupus nephritis.

Key words: mycophenolate mofetil, tacrolimus, multi-target therapy, , lupus nephritis