Rituximab versus cyclophosphamide as first steroid-sparing agent in childhood frequently relapsing and steroid-dependent nephrotic syndrome

Abstract

Background: Approximately 50% of children with steroid sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications. Methods:A prospective open label non-randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia or active infection. The recruited children were allocated either to the oral cyclophosphamide (3mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m 2 /dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months.Results: 46 subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.

Comparison of rituximab, cyclophosphamide, and tacrolimus as first steroid-sparing agents for complicated relapsing/steroid-dependent nephrotic syndrome in children: an evaluation of the health-related quality of life

“…Our study demonstrated a significant and clinically relevant reduction in the mean relapse rate during the 6 months after treatment with rituximab, tacrolimus, and cyclophosphamide compared to 6 months before treatment. The mean prednisolone dosage was significantly lower in all groups, confirming that these drugs are effective in minimizing relapse frequency in children with FRSDNS [1,2,7,8].…”

“…An RCT by Basu et al [8] reported a longer median time to first relapse with rituximab (40 weeks) than with tacrolimus (29 weeks). Another non-RCT showed a higher 1-year relapse-free survival with rituximab (84.2%) than cyclophosphamide (58.6%) [7]. Therefore, rituximab was more effective than cyclophosphamide and tacrolimus in prolonging the remission time.…”

“…Since 2004, several studies [5][6][7] have reported that rituximab, a chimeric anti-CD20 monoclonal antibody maintains remission in complicated FRSDNS. Sinha et al [5] showed that the median time to first relapse with single-dose of rituximab (375 mg/m 2 ) in children with SDNS and 2-4 doses were 16 and 18 months, respectively.…”

“…Sinha et al [5] showed that the median time to first relapse with single-dose of rituximab (375 mg/m 2 ) in children with SDNS and 2-4 doses were 16 and 18 months, respectively. More FRSDNS children achieved complete withdrawal of steroids within 3 months with rituximab as the first steroid-sparing agent than cyclophosphamide [7]. A comprehensive search of PubMed for relevant papers published before July 2021 found only three RCTs that documented a higher 1-year relapse-free survival rate and lower cumulative corticosteroid dose with rituximab than conventional drugs, MMF, and tacrolimus as the first steroid-sparing agent in children with SDNS [3,8,9].…”

Rhabdomyosarcoma in a child with nephrotic syndrome treated with cyclosporine: a case report with literature review

“…About 1-3% of children with nephrotic syndrome have frequent relapses or steroid-dependent nephrotic syndrome. Resistance to steroids or steroid toxicity often prompts administration of other immunosuppressive drugs, such as cyclosporine (CsA), cyclophosphamide, rituximab [3]. and others.…”