The use of low-dose cyclophosphamide followed by AZA/MMF treatment in childhood lupus nephritis

Abstract

Cyclophosphamide (CYC) has been the landmark in the treatment of lupus nephritis. However, long-term treatment with CYC is associated with significant side effects. We aimed to evaluate the efficacy of short-term intravenous (IV) CYC treatment as a remission induction treatment followed by azathioprine (AZA) or mycophenolate mofetil (MMF) as a maintenance treatment. Twenty patients (18 girls) with biopsy-proven class III (5) and IV (15) lupus nephritis were included in to the study. Detailed clinical and laboratory data and patient outcomes were evaluated. All patients received three methylprednisolone (MP) IV pulses, followed by oral prednisone 0.5-1 mg/kg per day and one IV pulse of CYC per month for 6 months. Azathioprine was started as a remission-maintaining treatment. In ten of 20 patients, treatment was switched to MMF. The mean age at the time of diagnosis was 16.11 +/- 3.49 years, and the mean duration of follow-up was 49.6 +/- 27 months. Fourteen patients (70%) had complete remission, three (15%) had partial remission, one (5%) continued to have active disease, and two (10%) progressed to end-stage renal disease. Nine of the patients (45%) with complete remission had received AZA, and switching to MMF increased complete remission rate (additional five patients; 25%). In conclusion, short-term (6-month) IV bolus CYC treatment followed by AZA is a safe and effective treatment in children with severe lupus nephritis, and using MMF increases remission rate in resistant cases.

Європейські Доказові Рекомендації По Діагностиці Та Лікуванню Люпус-Нефриту У Дітей: Ініціатива SHARE

“…However in observational studies of LN in adults rituximab has been successfully used as rescue treatment for refractory LN (78,79). Only very limited evidence for the use of rituximab for LN in cSLE was found in the literature search (37,48). Recently, an observational cohort study in cSLE reported the effects of rituximab treatment in 63 children, LN was the indication to start rituximab treatment in 36% of the patients.…”

“…In the majority of these articles I.V. CYC is used as induction treatment, with good results in the majority of patients (45)(46)(47)(48)(49)(50)(51)(52)(53). Three studies compared I.V.…”

“…As there is no robust evidence for the ideal dosing strategy of corticosteroids in proliferative LN in SLE or cSLE, the expert group has not specified this in a recommendation. Most studies in cSLE report the use of oral prednisone 1-2 mg/kg/day (maximum 60 mg/day) as initial dosing in proliferative LN where children < 30 kg mostly are dosed up to 2 mg/kg/day (38,47,48,52,53,64). I.V.…”

“…When combining the high-quality evidence from RCT for LN in adult-onset SLE with the evidence from smaller case series and observational cohort studies in cSLE, the expert group recommends MMF (1200-1800mg/m2/day, maximum 1500 mg twice daily) or I.V. CYC in combination with high-dose prednisone (1-2 mg/kg/day, maximum 60 mg/day) for induction treatment of proliferative LN in cSLE (10,(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). The dosing of I.V.…”

Off-patent Oral Oncology Drugs for Kids (O3K FP7-project): From bedside to PUMA

“…In addition, the role of cyclophosphamide has been further established in pediatric non-malignant diseases such as nephrotic syndrome (Azib et al, 2011) and lupus nephritis (Baskin et al, 2010).…”