American journal of kidney diseases : the official journal of the National Kidney Foundation · 2025
Response to Rituximab as a Maintenance Therapy in Adult Idiopathic Nephrotic Syndrome: A French Multicenter Cohort Study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Laslandes Manuel, Lorent Marine, Brilland Benoit, Boulay Hugoline, Golbin Léonard, Barbet Christelle, Grellier Jimmy, Dujardin Amaury, Larmet David, Testa Angelo, Pfirmann Pierre, Thierry Antoine, Ville Simon, Dantal Jacques, Masset Christophe
Аннотация
RATIONALE & OBJECTIVE: Rituximab effectively limits the number of relapses in childhood idiopathic nephrotic syndromes (INS) and reduces exposure to corticosteroids and other immunosuppressants. However, few data are available on the risk of relapse after an initial dose of rituximab or the benefit of a maintenance therapy in adults with INS.
STUDY DESIGN: Multicenter retrospective cohort study.
SETTING & PARTICIPANTS: All adult patients with minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) treated in 10 French centers who received a first dose of rituximab between January 2009 and June 2023.
EXPOSURE: Maintenance therapy with rituximab.
OUTCOME: Disease relapse, change in proteinuria, and occurrence of infectious complications ascertained using clinical, biological, and histological data collected from disease onset until up to 4 years after the first rituximab dose.
ANALYTICAL APPROACH: Marginal structural models of rituximab redosing and, as time-varying covariates, proteinuria, use of steroids, and other immunosuppressant drugs.
RESULTS: The study included 134 patients (MCD = 66.4%) who were followed for a median of 36 months after the first dose of rituximab (baseline). In a subgroup of patients followed for at least 2 years after baseline (n = 65), rituximab was associated with a significant reduction in the frequency of relapses (0.20 vs 1.02 per person-year; P < 0.001). Two-thirds of the 26 patients with baseline nephrotic proteinuria had decreased proteinuria within the first 6 months (median reduction of 70% [IQR, 46-94]). Among the 105 patients in remission at baseline, the median relapse-free survival was 38 months. Maintenance dosing of rituximab between 6 and 12 months after the first dose was associated with significantly lower risk of INS relapse during follow-up (HR, 0.35 [95% CI, 0.15-0.83], P = 0.02). Overall, the rate of severe infections was 7.24 per 100 person-years in the entire cohort. Treatment with rituximab after the first dose was not detectably associated with an increased risk of severe infections (HR, 0.48 [95% CI, 0.08-2.98], P = 0.4).
LIMITATIONS: Retrospective, observational study. Variation in doses/timing of rituximab. Heterogeneous population. Lack of longitudinal CD19 monitoring.
CONCLUSIONS: Rituximab reduced the risk for INS relapse, and maintenance treatment between 6 and 12 months was associated with further reduction in relapses. Prospective studies are required to better specify the benefit of rituximab maintenance therapy.
PLAIN-LANGUAGE SUMMARY: Rituximab is effective in reducing relapses and the need for administration of steroids and other immunosuppressant drugs in childhood idiopathic nephrotic syndromes (INS). In adults, few data are available, particularly with regard to maintenance dosing. This study identified all adult patients with INS who received rituximab in 10 French clinical centers. These 134 patients were followed for a median of 36 months. Rituximab was associated with a reduction in the number of relapses and exposure to steroids and other immunosuppressants. Maintenance dosing of rituximab between 6 and 12 months was significantly associated with a lower risk of INS relapse without an increased risk of severe infections. The role of maintenance therapy with rituximab requires further evaluation in prospective studies.
STUDY DESIGN: Multicenter retrospective cohort study.
SETTING & PARTICIPANTS: All adult patients with minimal change disease (MCD) or primary focal segmental glomerulosclerosis (FSGS) treated in 10 French centers who received a first dose of rituximab between January 2009 and June 2023.
EXPOSURE: Maintenance therapy with rituximab.
OUTCOME: Disease relapse, change in proteinuria, and occurrence of infectious complications ascertained using clinical, biological, and histological data collected from disease onset until up to 4 years after the first rituximab dose.
ANALYTICAL APPROACH: Marginal structural models of rituximab redosing and, as time-varying covariates, proteinuria, use of steroids, and other immunosuppressant drugs.
RESULTS: The study included 134 patients (MCD = 66.4%) who were followed for a median of 36 months after the first dose of rituximab (baseline). In a subgroup of patients followed for at least 2 years after baseline (n = 65), rituximab was associated with a significant reduction in the frequency of relapses (0.20 vs 1.02 per person-year; P < 0.001). Two-thirds of the 26 patients with baseline nephrotic proteinuria had decreased proteinuria within the first 6 months (median reduction of 70% [IQR, 46-94]). Among the 105 patients in remission at baseline, the median relapse-free survival was 38 months. Maintenance dosing of rituximab between 6 and 12 months after the first dose was associated with significantly lower risk of INS relapse during follow-up (HR, 0.35 [95% CI, 0.15-0.83], P = 0.02). Overall, the rate of severe infections was 7.24 per 100 person-years in the entire cohort. Treatment with rituximab after the first dose was not detectably associated with an increased risk of severe infections (HR, 0.48 [95% CI, 0.08-2.98], P = 0.4).
LIMITATIONS: Retrospective, observational study. Variation in doses/timing of rituximab. Heterogeneous population. Lack of longitudinal CD19 monitoring.
CONCLUSIONS: Rituximab reduced the risk for INS relapse, and maintenance treatment between 6 and 12 months was associated with further reduction in relapses. Prospective studies are required to better specify the benefit of rituximab maintenance therapy.
PLAIN-LANGUAGE SUMMARY: Rituximab is effective in reducing relapses and the need for administration of steroids and other immunosuppressant drugs in childhood idiopathic nephrotic syndromes (INS). In adults, few data are available, particularly with regard to maintenance dosing. This study identified all adult patients with INS who received rituximab in 10 French clinical centers. These 134 patients were followed for a median of 36 months. Rituximab was associated with a reduction in the number of relapses and exposure to steroids and other immunosuppressants. Maintenance dosing of rituximab between 6 and 12 months was significantly associated with a lower risk of INS relapse without an increased risk of severe infections. The role of maintenance therapy with rituximab requires further evaluation in prospective studies.