Mycophenolate for treatment of lupus nephritis refractory to cyclophosphamide

Mycophenolate 用於cyclophosphamide 治療無效狼瘡性腎炎之研究

前言：近來有關mycophenolate 對狼瘡性腎炎治療的研究報告，大多顯示令人振奮的結果，本研究的目的是在評估其治療cyclophosphamide無效之狼瘡性腎炎的效果及安全性。方法：本研究的16位病患，皆是在先前使用過cyclophosphamide，且治療無效的狼瘡性腎炎患者，mycophenolate的初始劑量皆為0.5克／天，若無效則慢慢增加至最高劑量 1克／天。統計分析其效果的項目包括：每日蛋白尿量、血清肌苷酸、補體C3、C4以及anti-dsDNA的量。結果：我們的研究發現，儘管病患的血清肌苷酸並無太大改變，其每日蛋白尿量於治療期間由4.99 ± 3.78克／天降低至2.82 ± 2.36克／天（p=0.04） 。狼瘡性腎炎的緩解率為44%，其中包括2人完全緩解；5人部份緩解。併用類固醇的劑量於6個月後由16.09 ± 8.16毫克／天，降低至11.41 ± 4.83毫克／天，其結果具有統計學意義 （p=0.028）。至於補體C3、C4以及anti-dsDNA的量則無明顯的改變，治療期間並無嚴重副作用產生。結論：對cyclophosphamide治療無效之狼瘡性腎炎的病患，低劑量mycophenolate （0.5 to 1克／天） 合併類固醇為一有效且安全的治療選擇。

Objective: Mycophenolate has recently been introduced as an immunosuppressive agent for treatment of nephritis in systemic lupus erythematosus (SLE) and the data has been encouraging. The present study aimed to investigate the efficacy and safety of mycophenolate for a group of SLE patients with nephritis who were refractory to cyclophosphamide treatment. Methods: We prospectively studied 16 SLE patients who had previously received cyclophosphamide therapy with uncontrolled lupus nephritis. The mycophenolate dose was started at 0.5 gm per day and was increased up to 1 gm if there was an inadequate response. Parameters measured in the study including daily proteinuria, serum creatinine, C3/C4 levels and anti-dsDNA titers were collected at entry to the study and at 3-month intervals. Results: The amount of daily urinary protein loss reduced significantly from 4.99 ± 3.78 gm to 2.82 ± 2.36 gm at the last visit (p=0.04) in spite of the significant absence of changes in serum creatinine levels. The remission rate was 44% included 2 cases of complete remission and 5 cases of partial remission. The concomitant oral prednisolone dose decreased significantly from 16.09 ± 8.16 mg/day to 11.41 ± 4.83 mg/day at 6 months (p=0.028). There were no significant changes in the levels of C3, C4 and anti-dsDNA antibodies. No severe adverse effects were observed in the study. Conclusion: Low dose mycophenolate (0.5 to 1 gm/d) combined with glucocorticoid appears to be a safe and effective therapy for some patients with lupus nephritis that do not respond to cyclophosphamide therapy in the Taiwanese patients with SLE.