Efficacy and safety of rituximab in antiglomerular basement membrane disease
File(s)
Author(s)
Type
Journal Article
Abstract
Introduction
Anti–glomerular basement membrane (GBM) disease is caused by pathogenic antibodies usually targeting the noncollagenous domain of the α3 chain of type IV collagen and frequently presents as rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage (DAH). Rapid reduction of these antibodies is imperative for kidney survival and the mainstay of therapy is the combination of plasma exchange (PLEX), glucocorticoids, and cyclophosphamide. Rituximab has been postulated as a potential treatment for anti-GBM disease; however, data on efficacy and safety are lacking.
Methods
We performed a review of case reports and series (n = 28) providing individual patient-level data on the efficacy and safety of rituximab in adult and pediatric anti-GBM disease. In addition, we have received data from authors on 18 patients which stem from 4 studies that did not report on patient-level outcomes or were not previously reported. A search strategy of studies indexed in PubMed/MEDLINE was performed, followed by synthesis and analysis of the data.
Results
Sixty-seven patients [37 female (55%); 14 pediatric (21%); median age: 37 years] were followed-up with for a total of 87.1 person-years (median follow-up time: 9.5 months). They received rituximab as first-line (n = 39) or second-line (n = 28). Median serum creatinine was 416 μmol/l with 32 patients (48%) being dialysis-dependent at presentation and 24 (36%) having DAH. Intravenous pulse, oral glucocorticoids and PLEX were used in 85%, 98%, and 93%, respectively; and 54% of them received cyclophosphamide. Patients received a median of 4 (2–4) doses of rituximab with 11 patients (16%) having transient adverse effects. Patient survival was 91% and kidney survival was 67% (53% in adults and 71% in pediatric patients). Kidney survival was lower in initially dialysis-dependent patients (34% vs. 81%, P < 0.001). Patients receiving second-line rituximab had better kidney survival compared with those receiving it as first-line (73% vs. 46%, P = 0.03).
Conclusion
Acknowledging the limitations of our study, including publication and selection bias, rituximab had a favorable toxicity and efficacy profile. The results indicate that rituximab can be considered as a second-line therapy in anti-GBM disease when cyclophosphamide is contraindicated.
Anti–glomerular basement membrane (GBM) disease is caused by pathogenic antibodies usually targeting the noncollagenous domain of the α3 chain of type IV collagen and frequently presents as rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage (DAH). Rapid reduction of these antibodies is imperative for kidney survival and the mainstay of therapy is the combination of plasma exchange (PLEX), glucocorticoids, and cyclophosphamide. Rituximab has been postulated as a potential treatment for anti-GBM disease; however, data on efficacy and safety are lacking.
Methods
We performed a review of case reports and series (n = 28) providing individual patient-level data on the efficacy and safety of rituximab in adult and pediatric anti-GBM disease. In addition, we have received data from authors on 18 patients which stem from 4 studies that did not report on patient-level outcomes or were not previously reported. A search strategy of studies indexed in PubMed/MEDLINE was performed, followed by synthesis and analysis of the data.
Results
Sixty-seven patients [37 female (55%); 14 pediatric (21%); median age: 37 years] were followed-up with for a total of 87.1 person-years (median follow-up time: 9.5 months). They received rituximab as first-line (n = 39) or second-line (n = 28). Median serum creatinine was 416 μmol/l with 32 patients (48%) being dialysis-dependent at presentation and 24 (36%) having DAH. Intravenous pulse, oral glucocorticoids and PLEX were used in 85%, 98%, and 93%, respectively; and 54% of them received cyclophosphamide. Patients received a median of 4 (2–4) doses of rituximab with 11 patients (16%) having transient adverse effects. Patient survival was 91% and kidney survival was 67% (53% in adults and 71% in pediatric patients). Kidney survival was lower in initially dialysis-dependent patients (34% vs. 81%, P < 0.001). Patients receiving second-line rituximab had better kidney survival compared with those receiving it as first-line (73% vs. 46%, P = 0.03).
Conclusion
Acknowledging the limitations of our study, including publication and selection bias, rituximab had a favorable toxicity and efficacy profile. The results indicate that rituximab can be considered as a second-line therapy in anti-GBM disease when cyclophosphamide is contraindicated.
Date Issued
2025-03-01
Date Acceptance
2024-12-23
Citation
Kidney International Reports, 2025, 10 (3), pp.743-752
ISSN
2468-0249
Publisher
Elsevier
Start Page
743
End Page
752
Journal / Book Title
Kidney International Reports
Volume
10
Issue
3
Copyright Statement
© 2024 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40225363
PII: S2468-0249(24)03466-1
Subjects
anti–glomerular basement membrane disease
glomerulonephritis
rituximab
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-12-30