Can Rituximab be Used As a First-Line Drug in Hormone-Dependent Nephrotic Syndrome
Idiopathic Nephrotic Syndrome is the most common glomerular dysfunction in pediatrics. Recurrence occurs in about 40% of children with idiopathic nephrotic syndrome and is usually associated with repeated use of glucocorticoid or glucocorticoid dependence. Calcineurin inhibitor (e.g. tacrolimus) have long been considered as a first-line drug to reduce hormone use in children with recurrent disease. B lymphocyte depletion agents, such as rituximab, are considered second-line therapies for people who have difficulty in remission.
Recently, JAMA Pediatrics published an open-label randomized controlled trial, which compared the efficacy of rituximab and tacrolimus in maintaining relapse-free survival in children with nephrotic syndrome to determine whether rituximab can be used as a first-line drug to reduce hormone use.
A total of 120 patients with hormone-dependent nephrotic syndrome were included in the study, with a median age of 7.1 years (3-16 years). About 70% renal biopsies showed minimal change disease and 30% patients were Focal Segmental Glomerulonephrosis (FSGS). All the subjects were not treated with hormone-reducing drugs before enrollment.
After enrollment, the patients were randomly divided into tacrolimus group (n=60) and rituximab group (n=60). The tacrolimus group was given daily tacrolimus + oral hormone every other day for 12 months. The rituximab group was given 2-4 times of rituximab (once every other week) + oral hormone every other day for 4 weeks, followed by 2 times/every other week. The primary endpoint was 12 months of relapse-free survival. Secondary endpoints were frequency of recurrence and time of first recurrence, and cumulative hormone use (mg/kg/ year).
Results found that recurrence-free survival rate was 89.8% in the rituximab group, significantly higher than that in the tacrolimus group (63.8%). Cumulative hormone use was 86.3 mg/kg/ year in the tacrolimus group and 25.8 mg/kg/ year in the rituximab group.
In terms of adverse events, there was no significant difference except for the infection rate, which was 43.3% in the tacrolimus group and 21.7% in the rituximab group. In the rituximab group, there were more transfusion reactions, but hospitalization was not required.
The study showed that compared with tacrolimus, rituximab was associated with a significantly reduced risk of recurrence in children with hormone-dependent nephrotic syndrome and was clinically significant, the researchers said.
Professor William t. Basco of the medical university of south Carolina commented on the findings that “I have encountered many of these patients in clinical practice, and the results of this study are of great clinical significance. Studies have shown that rituximab reduces the risk of relapse by 80%, the cumulative use of the hormone is one-third less than tacrolimus, and infection rates are lower. All results appear to support rituximab as a first-line drug for reducing hormone therapy.”
However, before it is widely used in clinical practice, I believe that more studies are needed to evaluate the similarities and differences among patients with different genomes, as well as long-term follow-up to evaluate the benefits and risks of rituximab (like pulmonary fibrosis, myocarditis, ulcerative colitis ). Adequate risk-benefit analysis is an important determinant of whether rituximab can be used as the preferred drug for children with hormone-resistant/dependent nephrotic syndrome.
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