Maintenance Therapy of Lupus Nephritis With MMF or AZA
Maintenance Therapy of Lupus Nephritis With MMF or AZA
In the present study we summarize the comparative data about the efficacy and safety of MMF and AZA as maintenance therapy for LN. These data are limited, but suggest no significant differences in the efficacy and safety of these drugs.
Our study has several limitations. First, the meta-analysis aggregated results from clinical trials with high heterogeneity in design, drug doses and treatment of the induction phase. Also, the quality of studies was low. Only one randomized, double-blind trial compared the efficacy and safety of MMF and AZA. Another important limitation was the heterogeneity in variable definitions. Our study has several strengths, including consistency and the absence of significant heterogeneity in the results and no significant risks of publication bias in the included articles.
A meta-analysis of safety was not done because of the low frequency of some events and the expression of events as IR per 100 patients-years. However, to analyse differences in safety the IRRs of the most frequent AEs were calculated for MMF compared with AZA.
MMF is used as an immunosuppressant in transplant medicine. It seems superior to AZA at preventing graft rejection. However, in our analysis, no significant differences were found in efficacy. Nevertheless, a meta-analysis of relapse as a surrogate for lack of efficacy suggests a lower risk for MMF. The one randomized, double-blind trial showed relapse with MMF was less frequent than with AZA.
Meta-analysis of mortality showed no differences between the MMF and AZA groups. Interestingly, discontinuation due to AEs was significantly lower with MMF than with AZA. The majority of patients treated with MMF as maintenance therapy were treated with MMF as induction therapy. Patients at risk of discontinuing because of AEs or inefficacy were probably excluded in the induction phase, hence their number in the maintenance phase was lower.
Results of subanalyses suggest a difference in response to the different regimens of induction and different populations. In patients with low estimated GFR, MMF may be faster in recovering kidney function compared with CYC. Also, MMF may present advantages in response in Black and Hispanic patients. However, these data could not be proved in the meta-analysis due to the small number of observations.
Although the safety profile of MMF and AZA was not significantly different, there were some variations. As expected, gastrointestinal AEs were more common with MMF and leucopoenia was more common with AZA. This is not surprising because these are common AEs of these drugs. Three malignancies were reported: two cervical carcinomas and one uterine carcinoma in situ in the AZA group. A relationship to previous use of CYC cannot be excluded.
In conclusion, no significant differences in efficacy and safety were seen between MMF and AZA as maintenance treatment of LN. Nevertheless, the high heterogeneity of the studies included in the analysis make this contention questionable.
Discussion
In the present study we summarize the comparative data about the efficacy and safety of MMF and AZA as maintenance therapy for LN. These data are limited, but suggest no significant differences in the efficacy and safety of these drugs.
Our study has several limitations. First, the meta-analysis aggregated results from clinical trials with high heterogeneity in design, drug doses and treatment of the induction phase. Also, the quality of studies was low. Only one randomized, double-blind trial compared the efficacy and safety of MMF and AZA. Another important limitation was the heterogeneity in variable definitions. Our study has several strengths, including consistency and the absence of significant heterogeneity in the results and no significant risks of publication bias in the included articles.
A meta-analysis of safety was not done because of the low frequency of some events and the expression of events as IR per 100 patients-years. However, to analyse differences in safety the IRRs of the most frequent AEs were calculated for MMF compared with AZA.
MMF is used as an immunosuppressant in transplant medicine. It seems superior to AZA at preventing graft rejection. However, in our analysis, no significant differences were found in efficacy. Nevertheless, a meta-analysis of relapse as a surrogate for lack of efficacy suggests a lower risk for MMF. The one randomized, double-blind trial showed relapse with MMF was less frequent than with AZA.
Meta-analysis of mortality showed no differences between the MMF and AZA groups. Interestingly, discontinuation due to AEs was significantly lower with MMF than with AZA. The majority of patients treated with MMF as maintenance therapy were treated with MMF as induction therapy. Patients at risk of discontinuing because of AEs or inefficacy were probably excluded in the induction phase, hence their number in the maintenance phase was lower.
Results of subanalyses suggest a difference in response to the different regimens of induction and different populations. In patients with low estimated GFR, MMF may be faster in recovering kidney function compared with CYC. Also, MMF may present advantages in response in Black and Hispanic patients. However, these data could not be proved in the meta-analysis due to the small number of observations.
Although the safety profile of MMF and AZA was not significantly different, there were some variations. As expected, gastrointestinal AEs were more common with MMF and leucopoenia was more common with AZA. This is not surprising because these are common AEs of these drugs. Three malignancies were reported: two cervical carcinomas and one uterine carcinoma in situ in the AZA group. A relationship to previous use of CYC cannot be excluded.
In conclusion, no significant differences in efficacy and safety were seen between MMF and AZA as maintenance treatment of LN. Nevertheless, the high heterogeneity of the studies included in the analysis make this contention questionable.
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