Efficacy and Safety of Rituximab in Antiglomerular Basement Membrane Disease
(2025) In Kidney International Reports 10(3). p.743-752- 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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2025-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- anti–glomerular basement membrane disease, glomerulonephritis, rituximab
- in
- Kidney International Reports
- volume
- 10
- issue
- 3
- pages
- 10 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:40225363
- scopus:85215391922
- ISSN
- 2468-0249
- DOI
- 10.1016/j.ekir.2024.12.026
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2024 International Society of Nephrology
- id
- c0a4b9c1-c036-4ba7-9440-857fb719b271
- date added to LUP
- 2025-05-06 09:47:29
- date last changed
- 2025-07-01 15:51:56
@article{c0a4b9c1-c036-4ba7-9440-857fb719b271, abstract = {{<p>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.</p>}}, author = {{Ivković, Vanja and Bajema, Ingeborg and Bruchfeld, Annette and McAdoo, Stephen and Kumar, Asheesh and Klaus, Richard and Kanzelmeyer, Nele and Touzot, Maxime and Maalouf, Georgina and Jaryal, Ajay and Vikrant, Sanjay and Haffner, Dieter and Lange-Sperandio, Bärbel and Saadoun, David and Segelmark, Mårten and Kronbichler, Andreas}}, issn = {{2468-0249}}, keywords = {{anti–glomerular basement membrane disease; glomerulonephritis; rituximab}}, language = {{eng}}, number = {{3}}, pages = {{743--752}}, publisher = {{Elsevier}}, series = {{Kidney International Reports}}, title = {{Efficacy and Safety of Rituximab in Antiglomerular Basement Membrane Disease}}, url = {{http://dx.doi.org/10.1016/j.ekir.2024.12.026}}, doi = {{10.1016/j.ekir.2024.12.026}}, volume = {{10}}, year = {{2025}}, }