POTENCY OF SINGLE VS DOUBLE DOSE RITUXIMAB IN DIFFICULT TO TREAT AND STEROID RESISTANT NEPHROTIC SYNDROME AMONG CHILDREN AGED 5 YEARS TO 18 YEARS

Introduction:

Objective –

To assess sustained remission in children aged 5 to 18 years with difficult-to-treat and steroid resistant nephrotic syndrome with single dose vs double dose of rituximab.

Introduction –

Nephrotic syndrome (NS) is the most prevalent kidney diseases affecting children. Its occurrence is documented to be 2–3/100000 children in western nations, while it's slightly elevated (9–10/100000) among Indian children, with a prevalence of 12–16/100000 children. Diagnosis involves a combination of clinical indicators such as massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Though corticosteroids remain the primary treatment for NS, remission is attained only in 85-90% in Steroid Sensitive Nephrotic Syndrome and rest falls into the category where they require additional immunosuppression like levamisole, cyclophosphamide, MMF (Mycophenolate mofetil), CNI (Calcineurin Inhibitors) and Rituximab. The Indian Society of Pediatric Nephrology (ISPN) 2021 guidelines recommend the use of CNI (tacrolimus or cyclosporine) or rituximab in the treatment of difficult to treat nephrotic syndrome and in steroid resistant nephrotic syndrome. In our study we have analysed the potency of single vs double dose rituximab to maintain sustained remission in difficult to treat and steroid resistant nephrotic syndrome.

Methods:

Baseline characteristics including Age, sex, blood pressure, eGFR Clinical and histopathological types of nephrotic syndrome, immunosuppression before and after rituximab therapy were taken into consideration. Descriptive study was conducted in children among 5 - 18 years of age presenting to our tertiary care center. Inclusion: Children (5 - 18 years of age) with primary nephrotic syndrome who were receiving treatment for difficult-to-treat and steroid resistance were included in the study. Exclusion: Children with genetic basis of nephrotic syndrome or congenital nephrotic syndrome and secondary nephrotic syndrome. Ethical committee clearance and consent were taken.

Fig. 1 Recruitment of study subjects - 

Data entry was done in Microsoft excel. Demographic variables in categorical / dichotomous were given as frequencies with their percentages. Data analysis was done using IBM SPSS version 19. Descriptive statistics such as mean (SD) / median (IQR) and frequency(percentages) were used for quantitative measurements and qualitative data respectively. Shapiro wilk test was used to evaluate the normality of the data. To compare between the groups, independent t test was used for the normally distributed data and Mann Whitney U test for the non-normally distributed data. To find the association between the categorical variables chi square test/Fishers exact test was used. Kaplan Meier curve was used to plot the relapse time and log rank test was done to check the significance. p value <0.05 was considered as significant.

Results:

In our study it is found that two doses of rituximab was able to maintain a sustained remission better than a single dose in difficult to treat and steroid resistant nephrotic syndrome. The relapse free survival rate at 6 months was similar in both the groups (93.3 % in single dose group vs 100% in two dose group) with one child relapsing at 6 months in single dose vs none in 2 doses group. The 9 and 12-months relapse free survival rate was significantly shorter in the single dose as compared to two doses group as depicted in Table1. All the patients in single dose group relapsed at the end of one year whereas only 7 relapsed in two doses group.

*Test of significance – Chi-square test. 

Table 1. Comparison of the relapse free survival rate at 6, 9 and 12 months among the study groups

The overall median (IQR) relapse-free period was 10 (8, 11) months in single dose whereas it was significantly higher in the two doses group ,being 12.5 (12,13) [(p0.001), (Table2)].

*Test of significance – Mann Whitney U test

Table 2. Comparing the median relapse free period between single vs. two doses group

The same was brought out in Kaplan-Meier survival analysis curve, having the duration of remission / the median relapse-free period among study groups. [ (Log-rank test p 0.001), (Fig.2)]

Group 1 – Single dose / Group 2 – two doses

Fig.2.Median relapse free period among those on single vs two doses of Rituximab

Duration taken to stop steroids post rituximab infusion

The duration taken to stop steroids in two doses group was 5.0 ± 2.29 months which was lower than that of single dose of rituximab being 6.53 ± 2.56 months which are similar among the groups (p 0 .095) [Table 3]

* Test of significance - Mann Whitney U test

Table 3. Duration taken to stop steroids post rituximab infusion

Conclusions:

Therapy with Rituximab induces and maintains remission effectively. Sustained remission enables the reduction of steroid doses. In our study two-dose regimen of rituximab, with each dose of 375 mg/m² administered one week apart, shows superior relapse free survival rate than single dose in treating difficult-to-treat and steroid-resistant nephrotic syndrome. Hence the recommendation from this study is administering 2 doses of rituximab at 375 mg/m² one week apart in concordance with the Indian Society of Pediatric Nephrology Guidelines and will help us to bring down the usage of other immunosuppressive drugs.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.