Session Type: Abstract Submissions (ACR)
Very longterm data are rarely reported in lupus nephritis (LN) trials, despite their pivotal importance to detect late poor renal outcomers and to identify early prognostic markers. Here we report the 10-year followup of the MAINTAIN Nephritis Trial, a randomized European-based open trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative LN.
105 patients suffering from Class IV or V LN were randomly assigned to receive AZA or MMF after induction therapy with glucocorticoids and intravenous (IV) cyclophosphamide (CY) (Euro-Lupus protocol ; 6 x 500mg fortnightly). The primary endpoint was time to renal flare. After a mean followup of 48 months, we reported that 25 and 19% of patients experienced a renal flare in the AZA and MMF group, respectively (NS) (Houssiau et al., ARD 2010). In March 2014, we collected the 10-year data. Survival curves were drawn according to Kaplan-Meier method and statistically tested by logrank test. Other statistical methods were used as appropriate.
Five patients died (3 MMF, 2 AZA), of whom 2 (1 MMF, 1 AZA) had reached ESRD. Two additional MMF patients developed ESRD. Out of the 105 patients, 41 suffered from at least one renal flare, without difference between the two groups (22 AZA, 19 MMF). Proteinuric and nephritic flares were equally distributed between groups. Time to renal flare (all, proteinuric and nephritic) did not differ (p=0.77 ; p=0.39 ; p=0.50). Out of the 100 living patients, 13 were lost-to-followup. For the 87 remaining patients, the mean (±SD) followup was 115 (±17) months. Additional IVCY was prescribed in only 17% of the patients, somewhat more frequently in the AZA group, although the difference was not statistically significant (p=0.2). Further use of MMF in the AZA group and further use of AZA in the MMF group occurred in 33 and 26% of the patients, respectively. Patients were classified as good or poor longterm renal outcomers if their creatinine at last followup was ≤120% (n=83) or >120% (n=21) of baseline value, respectively. Interestingly, while their baseline 24-h proteinuria did not differ, patients with good longterm renal outcome had a much lower 24-h proteinuria at 3, 6 and 12 months compared to patients with poor outcome (p<0.0001 by ANOVA). Results were similar if different definitions of poor longterm renal outcome were used (eGFR below 60ml/min/1.72m2BSA, creatinine ≥1.0mg/dl or ≥1.4mg/dl). The positive predictive value of a uP/C ratio <0.5mg/mg at 3, 6 and 12 months for a good longterm renal outcome was excellent (89, 90 and 92%, respectively). By contrast, the negative predictive value was low (21, 29 and 32%, respectively), since many patients without an early proteinuria drop also achieved a good longterm renal outcome.
The longterm followup data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA for renal flare prevention in a Caucasian population suffering from proliferative LN. Moreover, we confirm the excellent positive predictive value of an early proteinuria drop for longterm renal outcome.
M. D. M. Ayala Gutierrez,
I. M. Gilboe,
V. le Guern,
F. A. Houssiau,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-10-year-followup-of-a-trial-comparing-azathioprine-and-mycophenolate-mofetil-for-long-term-immunosuppression-of-lupus-nephritis/