Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy.

Abstract

Background and objectiveThe rate of end-stage renal disease from lupus nephritis has not declined, in spite of recent advances in therapeutics, such as mycophenolate mofetil (MMF). To provide insight into rates of the clinical outcomes in current practice after biopsy-proven lupus nephritis, we used a prospective cohort of the patients with newly diagnosed lupus nephritis, treated with MMF and observed their outcomes.MethodTwenty systemic lupus erythematosus (SLE) patients who began mycophenolate mofetil shortly after a biopsy-confirmed diagnosis of lupus nephritis were included in the analysis. There were five patients with class III, nine with class IV, four with class III-V, one with class IV-V and two with class V lupus nephritis. The initial dose of mycophenolate mofetil was 1000 mg twice daily. If no improvement was observed, the dose was increased to 1500 mg twice daily after one month. We estimated the survival function for the time until the urine protein/creatinine reached 0.50 grams or less, after starting MMF by using an approach that accommodated interval-censored data. We also evaluated the treatment response using five different sets of criteria for the response that have previously been used in the clinical trials. These included the Bristol Myers-Squibb (BMS), the American College of Rheumatology (ACR), the lupus nephritis assessment with rituximab (LUNAR ), the Aspreva Lupus Management Study (ALMS), and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS).ResultWe estimated that 52% of the SLE patients reached 0.50 grams of proteinuria within 51 days of starting mycophenolate mofetil (95% confidence interval 29%-74%) and 77% reached 0.50 grams or less within 260 days (95% confidence interval 57%-97%). The probability of response at 90 and 180 days was 5% and 33% (the Bristol Myers-Squibb), 26% and 57% (the American College of Rheumatology), and 11% and 28% (the lupus nephritis assessment with rituximab, the Aspreva Lupus Management Study and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study).ConclusionThe complete renal response ranged from 28% to 57% at six months in the routine clinical practice, mirroring the results in randomized clinical trials. Regardless of the response measures, the complete renal response was slow and, by most indices, reached in only a minority of the patients by the end of six months of the induction therapy. This indicates the urgent need for the faster and more effective lupus nephritis treatments.