Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium

Abstract

Aims: Mycophenolate mofetil is an effective therapy for lupus nephritis (LN) and other glomerulonephritis (GN). However, gastrointestinal (GI) complications can limit its use. Enteric-coated mycophenolate sodium (EC-MPS) has been designed to reduce GI adverse events, but it has not been fully investigated in the treatment of GN. Methods: Patients with LN and primary GN who had received EC-MPS were studied for effects on renal function. Results: 30 subjects (17 LN, 13 primary GN) were studied. ECMPS decreased proteinuria in both LN and GN. In LN, 16 patients had EC-MPS as induction therapy. Of these, 8 patients achieved complete remission (CR), 4 had partial remission (PR) and 1 improved renal function. In primary GN, CR was achieved in 4 out of 5 with minimal change disease, but only 1 did not relapse. PR was achieved in 1 of 4 patients with membranous glomerulopathy, 2 out of 2 patients with focal segmental glomerulosclerosis and 1 out of 2 patients with IgA nephropathy. Infections, anemia and alopecia were observed, but no patient had GI side effects. Conclusions: EC-MPS is effective in LN, but not as effective in primary GN. The risk of GI side effects appears to be low, but other side effects can still occur. © 2008 Dustri-Verlag Dr. K. Feistle.AdverseEffects:6 patients developed adverse events (AEs), leading to EC-Myfortic withdrawal in 2 patients. 1 patient died following the development of pneumonia and cellulitis. AEs reported were anemia and TB meningitis (1), alopecia (2), decreased WBC count (2), leukopenia (1), and transient leukopenia and shingles (1). None of the patients developed gastrointestinal (GI) AEs.AuthorsConclusions:In conclusion, EC-MPS [mycophenolate sodium] appeared to be an effective induction therapy in lupus nephritis both as a first line agent and in cases resistant to cyclophosphamide. By contrast, EC-MPS appeared to be less effective in primary glomerulonephritis. In lupus nephritis, EC-MPS could be considered in patients who develop gastrointestinal symptoms with MMF. Other side effect profiles of EC-MPS appeared to be similar to MMF [mycophenolate mofetil]. More randomized controlled studies are necessary to confirm the benefits of this drug, both with regards to its efficacy and GI safety in primary GN and lupus nephritis.FreeText:Tests: serum creatinine (sCr), albumin and complement C3 and C4 levels, glomerular filtration rate (GFR), urine protein (creatinine), protein/creatinine excretion ratio, kidney biopsy, urine red blood cells, and white blood cell (WBC) count. Concomitant drugs: enalapril (n=6), losartan (n=1), candesartan (n=1), and corticosteroid (prednisolone). Other treatment: low sodium diet.Indications:17 patients with lupus nephritis (WHO Class IV 12 and WHO Class V 4) and 13 patients with primary glomerulonephritis (minimal-change disease 5, membranous glomerulopathy 4, IgA nephropathy 2 and focal segmental glomerulosclerosis 2).Patients:30 patients, 12 male and 18 female. LN group: 17 patients, 3 male and 14 female, aged 14 to 50 years (mean, 23 years). 1 dropout due to side effects. Primary GN group: 13 patients, 9 male and 4 female, aged 29 to 67 years (mean, 42 years). 1 dropout due to side effects.TypeofStudy:This study examined the efficacy and safety of enteric-coated (EC)-Myfortic in patients with lupus nephritis (LN) and primary glomerulonephritis (GN). Retrospective study.DosageDuration:LN group: initial dose, 360 to 1440 mg daily (mean, 1080 mg daily); maximum dose, 720 to 2160 mg daily (mean, 1080 mg daily); and maintenance dose, 360 to 2160 mg daily (mean, 1080 mg daily). Duration: 6 to 17 months (mean, 11 months). Primary GN group: initial dose, 360 to 1080 mg daily (mean, 1080 mg daily); maximum dose, 1080 to 1440 mg daily (mean, 1080 mg daily); and maintenance dose, 1080 to 1440 mg daily (mean, 1080 mg daily). Duration: 3 to 20 months (mean, 7 months).Results:Following EC-Myfortic therapy, 5/17 and 4/17 LN patients had renal insufficiency at the start and at the end of treatment, respectively. 2/17 and 1/17 patients had >0.5 mg/dL decrease and increase in sCr, respectively. GFR increased from 80.9 to 102.1 ml/minute/1.73 m2. Based on urine dipstick analysis and sCr, 1/17 and 1/17 patient had improved renal function and did not respond, respectively. Following EC-Myfortic therapy, proteinuria decreased from mean 3.2 to 0.8; serum albumin increased from 3.0 to 3.7 g/dL (p<0.001 and p<0.05, respectively). Urinary red blood cells decreased from 4 to 1/hpf, while serum C3 and C4 complement levels increased from 560 to 1038 and 69 to 234 mcg/mL (p<0.05, p<0.01, and p<0.01, respectively). 1/17 patient was successfully maintained in complete remission (CR) following conversion to EC-Myfortic therapy, while 8/16, 4/16, and 1/16 patients receiving EC-Myfortic induction therapy achieved CR, partial remission (PR), and improved renal function, respectively. However, 1/16 and 1/16 patient showed decline in renal function and had no response, respectively. 7/8, 4/8, 2/8, and 1/8 patient/s given initial EC-Myfortic induction either as a new case or as relapse derived benefit, had CR, PR, and had improved renal function, respectively. 5/8, 3/8, 2/8, 1/8, and 1/8 patient/s with resistant LN derived benefit, had CR, PR, had decline in renal function, and had no response, respectively. 3/4 and 1/4 patients with WHO Class V LN achieved CR and PR, respectively. 2/3 patients with primary GN who had renal insufficiency at the start had renal insufficiency at the end of EC-Myfortic therapy. No patient had >0.5 mg/dL change in sCr while GFR increased from 61.2 to 71.4 mL/minute/1.73 m2 from start to the end of treatment (p<0.05). Proteinuria, serum albumin, and urine red blood cells changed, increased, and decreased from 4.7 to 1.2, 3.7 to 3.9 g/dL, and 8 to 3.0/hpf (p<0.05, p<0.05, and p<0.05, respectively). Overall, 4/5 patients given combined EC-Myfortic and corticosteroid therapy achieved CR. 1 patient was able to discontinue corticosteroid without relapse while another patient with steroid-resistant minimal-change disease achieved CR following EC-Myfortic therapy but remained steroid-dependent with multiple relapses once prednisolone was reduced. 1/3 patient with steroid-dependent nephrotic syndrome (NS) achieved CR and was able to discontinue steroids for more than 3 months while on EC-Myfortic therapy. He previously had steroid-dependent NS for 12 years. 3/4 patients with membranous glomerulopathy did not achieve remission, while 1 patient with relapsed NS achieved PR with EC-Myfortic monotherapy. 1 patient with focal segmental glomerulosclerosis achieved PR with combined EC-Myfortic and high-dose corticosteroid while another patient achieved PR following addition of EC-Myfortic without increasing the dose of his corticosteroids. 1 patient with subnephrotic proteinuria showed decreased urine red blood cells without remission; another patient had PR following EC-Myfortic therapy.