Mycophenolate mofetil (MMF) and levamisole are common treatment choices in idiopathic frequently ... more Mycophenolate mofetil (MMF) and levamisole are common treatment choices in idiopathic frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS) in children and adolescents. We performed a randomized clinical trial to compare the efficacy and safety of MMF and levamisole in these conditions. Prospective open-label, multicenter, parallel-arm, blind-end point randomized clinical trial. 112 children and adolescents (64 FRNS and 48 SDNS) with estimated glomerular filtration rates > 80mL/min/1.73m(2) who were in remission (proteinuria with protein excretion < 100mg/dL for ≥3 days) followed up at 2 tertiary-care hospitals in Eastern India. MMF, 1,200mg/m(2), per day (n=56) or levamisole, 2.5mg/kg, on alternate days (n=56) for 12 months, along with tapering doses of alternate-day prednisolone (1.5mg/kg for 4 weeks following remission, then reduced by 0.25mg/kg every 2-4 weeks). The primary outcome was 12-month relapse-free survival in the intention-to-treat population (relapse: dipstick 3-4+ on 3 consecutive morning urine specimens). Prespecified secondary outcomes were relapse frequency, time to first relapse, cumulative prednisolone dosage, and adverse-effect profiles. 124 (1.1±1.2 per patient) and 190 (1.7±1.5 per patient) relapses occurred during the study period in the MMF and levamisole arms, respectively (P<0.001). Relapse frequency during the study period was lower than during the prestudy year (5.4±2.8 and 5.5±1.9, respectively; both P<0.001). MMF was associated with a higher rate of 12-month relapse-free survival than levamisole (38% vs 16%; P=0.003) and 33% lower cumulative prednisolone intake than levamisole (45.7±29.7 vs 67.8±35.8mg/kg per year; P<0.001). 64% of patients in the MMF arm versus 46% in the levamisole arm were off steroid therapy at 12 months. Whereas levamisole therapy was devoid of adverse effects, diarrhea occurred in 7% of MMF-treated patients, necessitating treatment discontinuation in 1 patient. Therapeutic drug monitoring for MMF was not routinely performed. MMF is equally safe and more efficacious than levamisole in maintaining remission and reducing cumulative steroid dose in children and adolescents with idiopathic FRNS and SDNS.
Rituximab is being increasingly used in children with idiopathic nephrotic syndrome resistant to ... more Rituximab is being increasingly used in children with idiopathic nephrotic syndrome resistant to standard treatments. In spite of good initial response, rituximab responders always remain prone to further relapse, necessitating either repeat course of rituximab or addition of another steroid-sparing immunosuppressant. A retrospective analysis of baseline clinico-pathologic presentation and treatment outcome (complete remission, partial remission, or no response) was performed among 24 children with refractory-idiopathic SRNS over a follow-up period of 24 months. Children received 2 to 4 rituximab infusions (375 mg/m(2) weekly) depending on circulating B-cell level. At 3-month follow-up, a second course of rituximab was administered (if >5 B cells/mm(3)) along with MMF (1200 mg/m(2) per day) maintenance therapy. Of 24 patients, 54% (13/24) and 46% (11/24) had minimal change disease and focal segmental glomerulosclerosis, respectively, on renal histopathology. After the first cours...
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015
Microscopic polyangiitis (MPA) is one of the most common forms of antineutrophil cytoplasm autoan... more Microscopic polyangiitis (MPA) is one of the most common forms of antineutrophil cytoplasm autoantibodies (ANCA)-associated vasculitis in children. Cyclophospamide and glucocorticoid-based treatment protocols are still considered gold standard in managing this multi-system disorder. But treatment-related toxicity is a major cause of chronic morbidity and early mortality in MPA. Hence, the search for an effective and safe alternative immunosuppressant is essential. A retrospective analysis of baseline clinico-pathological presentation and treatment-outcome was performed among 11 paediatric MPA patients. All of whom were treated with a pre-specified cyclophosphamide free, rituximab- and mycophenolate mofetil (MMF)-based management protocol as per centre practice. We describe the clinical course of 11 children with MPA over a median follow-up period of 20.9 months. Both patient survival and renal survival at 1 year follow-up were 100%. In spite of the varying degree of renal involvemen...
Mycophenolate mofetil (MMF) and levamisole are common treatment choices in idiopathic frequently ... more Mycophenolate mofetil (MMF) and levamisole are common treatment choices in idiopathic frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS) in children and adolescents. We performed a randomized clinical trial to compare the efficacy and safety of MMF and levamisole in these conditions. Prospective open-label, multicenter, parallel-arm, blind-end point randomized clinical trial. 112 children and adolescents (64 FRNS and 48 SDNS) with estimated glomerular filtration rates > 80mL/min/1.73m(2) who were in remission (proteinuria with protein excretion < 100mg/dL for ≥3 days) followed up at 2 tertiary-care hospitals in Eastern India. MMF, 1,200mg/m(2), per day (n=56) or levamisole, 2.5mg/kg, on alternate days (n=56) for 12 months, along with tapering doses of alternate-day prednisolone (1.5mg/kg for 4 weeks following remission, then reduced by 0.25mg/kg every 2-4 weeks). The primary outcome was 12-month relapse-free survival in the intention-to-treat population (relapse: dipstick 3-4+ on 3 consecutive morning urine specimens). Prespecified secondary outcomes were relapse frequency, time to first relapse, cumulative prednisolone dosage, and adverse-effect profiles. 124 (1.1±1.2 per patient) and 190 (1.7±1.5 per patient) relapses occurred during the study period in the MMF and levamisole arms, respectively (P<0.001). Relapse frequency during the study period was lower than during the prestudy year (5.4±2.8 and 5.5±1.9, respectively; both P<0.001). MMF was associated with a higher rate of 12-month relapse-free survival than levamisole (38% vs 16%; P=0.003) and 33% lower cumulative prednisolone intake than levamisole (45.7±29.7 vs 67.8±35.8mg/kg per year; P<0.001). 64% of patients in the MMF arm versus 46% in the levamisole arm were off steroid therapy at 12 months. Whereas levamisole therapy was devoid of adverse effects, diarrhea occurred in 7% of MMF-treated patients, necessitating treatment discontinuation in 1 patient. Therapeutic drug monitoring for MMF was not routinely performed. MMF is equally safe and more efficacious than levamisole in maintaining remission and reducing cumulative steroid dose in children and adolescents with idiopathic FRNS and SDNS.
Rituximab is being increasingly used in children with idiopathic nephrotic syndrome resistant to ... more Rituximab is being increasingly used in children with idiopathic nephrotic syndrome resistant to standard treatments. In spite of good initial response, rituximab responders always remain prone to further relapse, necessitating either repeat course of rituximab or addition of another steroid-sparing immunosuppressant. A retrospective analysis of baseline clinico-pathologic presentation and treatment outcome (complete remission, partial remission, or no response) was performed among 24 children with refractory-idiopathic SRNS over a follow-up period of 24 months. Children received 2 to 4 rituximab infusions (375 mg/m(2) weekly) depending on circulating B-cell level. At 3-month follow-up, a second course of rituximab was administered (if >5 B cells/mm(3)) along with MMF (1200 mg/m(2) per day) maintenance therapy. Of 24 patients, 54% (13/24) and 46% (11/24) had minimal change disease and focal segmental glomerulosclerosis, respectively, on renal histopathology. After the first cours...
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015
Microscopic polyangiitis (MPA) is one of the most common forms of antineutrophil cytoplasm autoan... more Microscopic polyangiitis (MPA) is one of the most common forms of antineutrophil cytoplasm autoantibodies (ANCA)-associated vasculitis in children. Cyclophospamide and glucocorticoid-based treatment protocols are still considered gold standard in managing this multi-system disorder. But treatment-related toxicity is a major cause of chronic morbidity and early mortality in MPA. Hence, the search for an effective and safe alternative immunosuppressant is essential. A retrospective analysis of baseline clinico-pathological presentation and treatment-outcome was performed among 11 paediatric MPA patients. All of whom were treated with a pre-specified cyclophosphamide free, rituximab- and mycophenolate mofetil (MMF)-based management protocol as per centre practice. We describe the clinical course of 11 children with MPA over a median follow-up period of 20.9 months. Both patient survival and renal survival at 1 year follow-up were 100%. In spite of the varying degree of renal involvemen...
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