The efficacy and safety of rituximab in treating childhood nephrotic syndrome: an Italian perspective

Abstract

BackgroundNephrotic syndrome is a disorder characterized by proteinuria, hypoalbuminemia and dyslipidemia. Low-dose alternate-day steroid regimen is the standard of care. In case of relapse or significant adverse events, steroid-sparing agents may be used. This analysis was aimed at assessing the efficacy and safety of rituximab for the treatment of children with nephrotic syndrome.ResultsFour studies were included in the final meta-analysis. The end-point of our analysis was the percentage of patients in remission at 6 months. Pooled data from the four studies favours the use of rituximab (RR 5.25, 95 % CI: 3.05–9.06; p < 0.0001). As regards the safety data, rituximab has a limited number of adverse effects, the most common of which occur during the infusions.ConclusionsIn Italy, the off-label use of drugs is regulated by Law 648/96. In our opinion, there are three scientific requirements to merit a conditional national reimbursement for rituximab in nephrotic syndrome: 1. favourable clinical efficacy and safety data; 2. no available alternatives; 3. outcome data collecting by AIFA through prescribers. In conclusion, our results report a significant incremental benefit of adding rituximab to corticosteroid and/or calcineurin inhibitors for the treatment of nephrotic syndrome.

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

“…The largest randomized placebo-controlled trial of RTX in NS administered four weekly doses of 375 mg/m 2 , reporting a median relapse-free period of 267 days in the RTX group compared to 101 days with placebo (hazard ratio 0.27, p = < 0.0001) [ 14 ]. Two meta-analyses of RTX in pediatric NS both demonstrated an improved relapse-free survival with RTX compared to other immunotherapies (relapse-free survival hazard ratio of 0.49 ( p = 0.03)) [ 26 ] and relative risk of remaining relapse-free at 6 months of 5.25, p < 0.0001) [ 27 ].…”

Advances in paediatrics in 2016: current practices and challenges in allergy, autoimmune diseases, cardiology, endocrinology, gastroenterology, infectious diseases, neonatology, nephrology, neurology, nutrition, pulmonology

“…Resistance to steroids and all immunosuppressive agents may also occur in a proportion of affected patients, and in these cases refractory steroid-resistant nephrotic syndrome, a condition with substantial risk of end-stage renal failure, has been described. Maratea et al [ 75 ] carried out an analysis aimed at assessing the efficacy and safety of rituximab, a chimeric anti-CD20 monoclonal antibody, for the treatment of children with nephrotic syndrome. The inclusion criteria of the studies were: a) a study population of children with complicated frequently relapsing/steroid-dependent nephrotic syndrome; b) the choice of rituximab as treatment; c) the choice of steroids and/or calcineurin inhibitors as control therapy; d) complete remission rate as end-point.…”

Efficacy and Safety of rituximab in children with difficult-to-treat nephrotic syndrome; a systematic review

“…That study concluded significant gradual benefits for the treatment of NS by adding RTX to corticosteroid and/or calcineurin inhibitors. In safety data they collected, RTX has a limited number of adverse effects; they showed that the most common of them occurred during the infusions, but that study included only randomized control trials and is thus different from our study (1). In our investigation, some studies such as (19) clearly explained the side effects of RTX (19).…”

“…Nephrotic syndrome (NS) is a complication diagnosed by heavy proteinuria, hypoalbuminemia (serum albumin <2.5 g/dL), often associated with hypercoagulability and dyslipidemia. According to the NS clinical guidelines, for the management of children who develop frequentlyrelapsing NS (FRNS) or steroid-dependent NS (SDNS), a low-dose alternate day steroid regimen, as the first-line treatment, is prescribed (1). Long-term glucocorticoid use in FRNS/SDNS patients leads to reduced bone mineral density, hypertension, increased infection risks, comorbidities such as cushingoid habitus, growth retardation, striae and acne, cataracts, pseudotumor cerebri, impaired glucose tolerance and hypercholesterolemia (2).…”