Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy?
Abstract
:1. Introduction
2. Rational and Mechanisms of Action of Rituximab
3. Rituximab Therapy in Nephrotic Syndrome
4. Pitfalls and Open Issues of Rituximab Therapy in Nephrotic Syndrome
5. The Nephrotic Syndrome and Rituximab Plasma Levels
6. The Correlation between CD19+ Depletion and Treatment Response
7. High-Sensitivity Flow Cytometric Cell Counting for Immune Monitoring of Anti-CD20 Therapies
8. High-Sensitivity Flow Cytometric Cell Counting in Clinical Practice
9. New Anti-CD20 Targeted Therapies for Nephrotic Syndrome
10. Future Developments
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CLINICAL TRIAL | GEMRITUX [23] | MENTOR [24] | STARMEN [27] | RI-CYCLO [28] |
---|---|---|---|---|
Country | France | The United States and Canada | Spain, France and the Netherlands | Italy and Switzerland |
Publication Year | 2017 | 2019 | 2020 | 2021 |
Randomized patients (n) | 75 | 130 | 86 | 74 |
Inclusion criteria |
|
|
|
|
Rituximab group | 375 mg/m2 on days 1 and 8 in association with NIAT |
|
|
|
Control group | NIAT |
|
|
|
Baseline characteristics: | ||||
| 56 | Around 52 | 55.7 | 55 |
| 76 | Around 90 | 78.5 | 76 |
| 7363.2 (4702.9–9735.0) | NA | NA | NA |
| NA | 8.9 (median) | 7.4 (median) | 6 |
| 68.6 | NA | 79.8 | 84 |
| NA | Around 86 | NA | NA |
| 73.3 | 73.8 | 77% | 66% |
Primary endpoint | Complete or partial remission of proteinuria at 6 months | Complete or partial remission of proteinuria at 24 months | Complete or partial remission of proteinuria at 24 months | Complete or partial remission of proteinuria at 12 months |
Primary outcome | n = 13 (35.1%; 95% [95% CI, 19.7 to 50.5) in the rituximab group and n = 8 (21.1%; 95% CI, 8.1 to 34.0) in the NIAT group; p = 0.21 | n = 39 (60%) in the rituximab group and n = 13 (20%) in the cyclosporine group (risk difference, 40 percentage points; 95% CI, 25 to 55; p < 0.001 for both non-inferiority and superiority). | n = 36 (83.7%) in the corticosteroid-cyclophosphamide group and n = 25 (58.1%) in the tacrolimus-rituximab group (RR 1.44; 95% CI 1.08 to 1.92) | n = 23 (62%) in the rituximab group and n = 27 (73%) receiving the cyclic regimen (OR, 0.61; 95% CI, 0.23 to 1.63). |
Anti–PLA2R-Ab trend | At 6 months deletion in13 of 26 (50%) in the rituximab group and 3 out of 25 (12%) in NIAT group (p = 0.004) | In the subgroup achieving partial or complete remission higher reduction of anti PLAR2 ab titre for rituximab group in comparison to cyclosporine at all-time points | Significant decrease in both treatment groups. A higher proportion of anti-PLA2R-positive patients achieved immunological response at 3 and 6 months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively) | Anti-PLA2R levels decreased in both arms during follow-up, more rapidly in the rituximab arm. |
Safety | Eight (21%) serious adverse events in each group | Serious adverse events in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (p = 0.06) | More adverse events and more adverse events per patient in the corticosteroids-cyclophosphamide group than in the tacrolimus-rituximab group (p = 0.04). | Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving SOFIJA the cyclic regimen. |
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Del Vecchio, L.; Allinovi, M.; Rocco, P.; Brando, B. Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy? J. Clin. Med. 2021, 10, 5847. https://doi.org/10.3390/jcm10245847
Del Vecchio L, Allinovi M, Rocco P, Brando B. Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy? Journal of Clinical Medicine. 2021; 10(24):5847. https://doi.org/10.3390/jcm10245847
Chicago/Turabian StyleDel Vecchio, Lucia, Marco Allinovi, Paolo Rocco, and Bruno Brando. 2021. "Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy?" Journal of Clinical Medicine 10, no. 24: 5847. https://doi.org/10.3390/jcm10245847