Efficacy and safety of enteric-coated mycophenolate sodium in combination with two glucocorticoid regimens for the treatment of active lupus nephritis

Abstract

Mycophenolic acid, in combination with glucocorticoids, has been shown in a series of trials to be safe and effective for treatment of lupus nephritis. Regimens that permit glucocorticoid dose reduction without loss of efficacy would be advantageous. MyLupus was a 24-week, multicentre, open-label, study in patients with active proliferative lupus nephritis treated with enteric-coated mycophenolate sodium (EC-MPS), randomized to standard-dose (n = 42) or reduced-dose (n = 39) glucocorticoids. Complete response at week 24, the primary endpoint, was achieved in 19.8% (16/81) of patients (19.0% standard-dose, 20.5% reduced-dose; lower limit of 97.5% CI for the difference -15.9%, p = 0.098, i.e. non-inferiority was not shown). Partial response occurred in 42.0% of patients (34/81). From baseline to week 24, the mean global British Isles Lupus Assessment Group (BILAG) score decreased from 14.0 ± 5.4 to 5.0 ± 3.8 (p < 0.001). The incidence of adverse events was 80.2% (65/81), most frequently gastrointestinal complications (31/81, 38.3%). Infections were reported in 57.1% and 35.9% of standard- and reduced-dose glucocorticoid patients, respectively (p = 0.056), with herpes zoster in 16.7% and 0% (p = 0.012). Three patients discontinued study medication due to adverse events. This exploratory study suggests that EC-MPS may facilitate glucocorticoid reduction without loss of efficacy in patients with active lupus nephritis, but results require confirmation in a controlled, longer-term study versus the current standard of care.

Comparison of high versus low–medium prednisone doses for the treatment of systemic lupus erythematosus patients with high activity at diagnosis

“…We have recently published good results using this scheme in patients with lupus nephritis, compared with controls from our historical cohort treated with high-dose prednisonecontaining regimes [8]. Similar data coming from other groups are encouraging [12][13][14].…”

“…≤30 mg/day) in the induction phase with rapid tapering to ≤5 mg/day compared with therapy using high doses [8,12,13]. We have recently shown a marked reduction in glucocorticoid-related side effects along with an earlier and more sustained renal response in patients treated with a medium-dose prednisone-containing regime combined with hydroxychloroquine, pulse methyl-prednisolone and immunosuppressive drugs (usually cyclophosphamide), compared with a standard NIH-like regime [8].…”

Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis

“…Nonetheless, the publication of the Aspreva Lupus Management Study (ALMS) trial,45 the largest trial in LN showing comparable response rates between MPA (target mycophenolate mofetil (MMF) dose 3 g/day) and intravenous cyclophosphamide (CY) (monthly pulses 0.5–1 g/m 2 ), both administered for 6 months, together with the ease of administration and the more favourable gonadal toxicity profile of the former,46–48 formed the basis for recommending MPA as initial treatment for most cases of class III–IV LN. Evidence from transplantation medicine49 50 and a single randomised controlled trial (RCT) in LN51 suggests that MMF and enteric-coated mycophenolic acid sodium (eMPA) are likely to be equally efficacious. To this end, and while awaiting further validation, the Committee felt that either MPA formulation can be used in treatment of LN, with 720 mg dose eMPA roughly equivalent to 1 g dose of MMF.…”

Update on the management of lupus nephritis

“…One study has evaluated the efficacy of conventional (1 mg/kg/d) versus low-dose (0.5 mg/kg/d) steroids in conjunction with a MPA (enteric-coated mycophenolate sodium, EC-MPS) as induction in severe, proliferative LN. It showed equal efficacy of both steroid regimens in inducing remission at 24 months [8].…”