Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

OBJECTIVE: To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. METHODS: In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. RESULTS: Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. CONCLUSIONS: The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome

Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial

Background: Long-term immunosuppressive treatment does not efficiently prevent relapses of lupus nephritis (LN). This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment. Methods: A total of 105 patients with lupus with proliferative LN were included. All received three daily intravenous pulses of 750 mg methylprednisolone, followed by oral glucocorticoids and six fortnightly cyclophosphamide intravenous pulses of 500 mg. Based on randomisation performed at baseline, AZA (target dose: 2 mg/kg/day) or MMF (target dose: 2 g/day) was given at week 12. Analyses were by intent to treat. Time to renal flare was the primary end point. Mean (SD) follow-up of the intent-to-treat population was 48 (14) months. Results: The baseline clinical, biological and pathological characteristics of patients allocated to AZA or MMF did not differ. Renal flares were observed in 13 (25%) AZA-treated and 10 (19%) MMF-treated patients. Time to renal flare, to severe systemic flare, to benign flare and to renal remission did not statistically differ. Over a 3-year period, 24 h proteinuria, serum creatinine, serum albumin, serum C3, haemoglobin and global disease activity scores improved similarly in both groups. Doubling of serum creatinine occurred in four AZA-treated and three MMF-treated patients. Adverse events did not differ between the groups except for haematological cytopenias, which were statistically more frequent in the AZA group (p=0.03) but led only one patient to drop out. Conclusions: Fewer renal flares were observed in patients receiving MMF but the difference did not reach statistical significance.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients.

Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades

Relapses of lupus nephritis: incidence, risk factors, serology and impact on outcome.

We prospectively followed a cohort of 46 newly diagnosed cases of lupus nephritis (LN) over a mean period of five years in order to determine the renal relapse rate, to identify potential risk factors for relapses, to assess the value of serological tests during flares and to analyse their impact on global outcome. Of the patients 37% experienced at least one renal flare, the first episode occurring after a mean follow-up of 40 months, when most patients were still treated with low-dose glucocorticoids and azathioprine. Baseline biochemical and pathological data did not differ between relapsing and nonrelapsing patients. Serological findings (low complement and high anti-DNA antibody) were less pronounced at relapse. Moreover, neither a decline in complement nor a rise in anti-DNA antibody titres were observed by the time of renal relapse, compared to immediate pre-flare values. Poor outcomes were observed only in relapsing patients. Taken together, renal relapses in LN patients are common, have a negative impact on outcome, but cannot be readily predicted. These results stress the importance of regular blood and urine examinations in LN patients, even years after the initial episode