Mycophenolate mofetil and systemic lupus erythematosus

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive agent which provides protection against acute transplant rejection, in patients who undergo kidney, heart and liver transplantation. Recently MMF has been used in various autoimmune conditions, including systemic lupus erythematosus (SLE). In SLE, MMF has been more extensively used in the treatment of proliferative lupus glomerulonephritis (GLN) and following the success in this field, it has also been used to control extra-renal manifestations. However, in the majority of cases MMF was administered to patients with refractory SLE manifestations and, therefore, no definite conclusion could be drawn from these experiences.In this paper, after a brief description of the mechanisms of action, the pharmacokinetics and metabolism of MMF which are relevant in SLE, and after a short discussion on the utility of performing therapeutic dose monitoring of mycphenolic acid, the experiences with the use of this drug in the different SLE manifestations were summarized and some personal data in patients with GLN were reported. Finally, the hypothetical use of MMF as a preventive strategy against the occurrence of severe manifestations in patients with mild SLE has been put forward and discussed. Lupus (2006) 15, 44-54.

Mycophenolate Mofetil in Lupus Glomerulonephritis

“…However, it has to be considered that the improvement of 24‐h proteinuria levels might be delayed in patients treated with CF. In fact, CF seems to have a carry‐over effect, as shown by the trials carried out at the National Institutes of Health in Bethesda 25–28 and also from our personal experience 29 …”

“…In our study of MMF as maintenance therapy for lupus GLN, 29 MMF was better tolerated than standard therapy (AZA or cyclosporine A). Moreover, no cases of discontinuation of therapy due to side effects were observed in the MMF group ( 2).…”

“…10,12,13,24 Furthermore, it has been showed that the use of MMF in the induction of remission in severe lupus GLN was associated with better quality of life than CF as perceived by patients, which was most likely attributed to the reduced side effects of MMF treatment. 32 In our study of MMF as maintenance therapy for lupus GLN, 29 MMF was better tolerated than standard therapy (AZA or cyclosporine A). Moreover, no cases of discontinuation of therapy due to side effects were observed in the MMF group (TABLE 2).…”

“…It is worth nothing that a significant reduction in 24‐h proteinuria occurred in both groups of patients not only after the induction treatment, but also after the subsequent 12 weeks, probably because of the above‐mentioned carry‐over effect of CF, without any difference among the maintenance drugs 29 . No significant variation in ECLAM score, 24‐h proteinuria levels, PDN cumulative dosage, and systolic and diastolic blood pressure were observed between the two treatment groups during the observational period.…”

“…In fact, CF seems to have a carry-over effect, as shown by the trials carried out at the National Institutes of Health in Bethesda [25][26][27][28] and also from our personal experience. 29 The study in which MMF was considered as maintenance therapy of GLN was performed by Contreras et al 13 The authors enrolled 59 patients with class III, IV, and V lupus GLN treated with I.V. CF as induction therapy.…”