Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome
Piero Ruggenenti1, Barbara Ruggiero, Paolo Cravedi
1IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo e Cele Daccò," Ranica, Bergamo, Italy;
Abstract:
The outcome of steroid-dependent or frequently relapsing nephrotic syndrome of minimal change disease (MCD), mesangial proliferative GN (MesGN), or FSGS may be poor and with major treatment toxicity. This academic, multicenter, off-on trial (ClinicalTrials.gov #NCT00981838) primarily evaluated the effects of rituximab therapy followed by immunosuppression withdrawal on disease recurrence in 10 children and 20 adults with MCD/MesGN (n=22) or FSGS who had suffered ≥2 recurrences over the previous year and were in steroid-induced remission for ≥1 month. Participants received one dose (n=28) or two doses of rituximab (375 mg/m(2) intravenously). At 1 year, all patients were in remission: 18 were treatment-free and 15 never relapsed. Compared with the year before rituximab treatment, total relapses decreased from 88 to 22 and the per-patient median number of relapses decreased from 2.5 (interquartile range [IQR], 2-4) to 0.5 (IQR, 0-1; P<0.001) during 1 year of follow-up. Reduction was significant across subgroups (children, adults, MCD/MesGN, and FSGS; P<0.01). After rituximab, the per-patient steroid maintenance median dose decreased from 0.27 mg/kg (IQR, 0.19-0.60) to 0 mg/kg (IQR, 0-0.23) (P<0.001), and the median cumulative dose to achieve relapse remission decreased from 19.5 mg/kg (IQR, 13.0-29.2) to 0.5 mg/kg (IQR, 0-9.4) (P<0.001). Furthermore, the mean estimated GFR increased from 111.3±25.7 to 121.8±29.2 ml/min per 1.73 m(2) (P=0.01), with the largest increases in children and in FSGS subgroups. The mean height z score slope stabilized in children (P<0.01). Treatment was well tolerated. Rituximab effectively and safely prevented recurrences and reduced the need for immunosuppression in steroid-dependent or frequently relapsing nephrotic syndrome, and halted disease-associated growth deficit in children.
Insights
Rituximab effectively prevents nephrotic syndrome relapses and reduces immunosuppression needs in children and adults. This therapy improved kidney function and halted growth deficits in pediatric patients, demonstrating a favorable safety profile.
Area of Science:
- Nephrology
- Immunology
- Pediatric Nephrology
Background:
- Steroid-dependent or frequently relapsing nephrotic syndrome (NS) associated with minimal change disease (MCD), mesangial proliferative GN (MesGN), or focal segmental glomerulosclerosis (FSGS) often has a poor prognosis.
- Current treatments carry significant toxicity, necessitating alternative therapeutic strategies.
- Rituximab has emerged as a potential treatment for relapsing NS, but its efficacy in withdrawing immunosuppression requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of rituximab therapy followed by immunosuppression withdrawal in preventing disease recurrence in patients with steroid-dependent or frequently relapsing nephrotic syndrome.
- To assess the impact of rituximab on the need for immunosuppressive medications, kidney function, and growth in children.
Main Methods:
- An academic, multicenter, off-on trial (ClinicalTrials.gov #NCT00981838) involving 30 patients (10 children, 20 adults) with MCD/MesGN or FSGS who experienced ≥2 relapses in the prior year.
- Patients received either one or two doses of rituximab (375 mg/m(2) intravenously) while in steroid-induced remission.
- Outcomes including disease recurrence, immunosuppression requirements, estimated glomerular filtration rate (eGFR), and growth parameters in children were monitored for 1 year.
Main Results:
- All patients achieved remission at 1 year; 18 were treatment-free, and 15 never relapsed.
- Total relapses significantly decreased from 88 to 22 compared to the year prior to rituximab (P<0.001).
- Rituximab treatment led to a significant reduction in steroid maintenance dose (P<0.001), increased mean eGFR (P=0.01), and stabilized growth in children (P<0.01).
Conclusions:
- Rituximab effectively and safely prevents recurrences in steroid-dependent or frequently relapsing nephrotic syndrome.
- Rituximab significantly reduces the reliance on immunosuppressive therapy, including steroids.
- The therapy demonstrates a positive impact on renal function and halts growth deficits in pediatric patients.
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