Maxime Touzot1, Johanne Poisson2, Stanislas Faguer3, David Ribes3, Pascal Cohen4, Loic Geffray5, Nadia Anguel6, Helene François7, Alexandre Karras8, Patrice Cacoub9, Antoine Durrbach7, David Saadoun10. 1. Service de néphrologie, IFRNT, Le Kremlin-Bicêtre, France. Electronic address: mtouzot@gmail.com. 2. Département de Médecine Interne et d'Immunologie clinique, Groupe Hospitalier Pitié-Salpêtrière, 84, boulevard de l'Hôpital, Paris 75013, France. 3. Département de Néphrologie et Transplantation d'Organes, Centre Hospitalo-Universitaire de Rangueil, Toulouse, France. 4. Service de Médecine interne, groupe hospitalier Cochin, Paris, France. 5. Service de médecine Interne CH lisieux, France. 6. Service de réanimation médicale, CHU Bicêtre, Le Kremlin-Bicêtre, France. 7. Service de néphrologie, IFRNT, Le Kremlin-Bicêtre, France; Institut National de la Santé et de la Recherche Médicale INSERM U1014 Villejuif, France. 8. Service de néphrologie, hôpital européen Georges-Pompidou, Paris, France. 9. Département de Médecine Interne et d'Immunologie clinique, Groupe Hospitalier Pitié-Salpêtrière, 84, boulevard de l'Hôpital, Paris 75013, France; Centre national de référence maladies systémiques et autoimmunes rares, DHU Inflammation, Immunopathologie, Biothérapie, Université Paris VI-Pierre et Marie Curie, Paris, France. 10. Département de Médecine Interne et d'Immunologie clinique, Groupe Hospitalier Pitié-Salpêtrière, 84, boulevard de l'Hôpital, Paris 75013, France; Centre national de référence maladies systémiques et autoimmunes rares, DHU Inflammation, Immunopathologie, Biothérapie, Université Paris VI-Pierre et Marie Curie, Paris, France. Electronic address: david.saadoun@pls.aphp.fr.
Abstract
OBJECTIVES: Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. METHODS: We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. RESULTS: Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. CONCLUSION: Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease.
OBJECTIVES: Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking. METHODS: We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy. RESULTS: Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported. CONCLUSION:Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease.
Authors: Marina Sánchez-Agesta; Cristina Rabasco; María J Soler; Amir Shabaka; Elisabeth Canllavi; Saulo J Fernández; Juan M Cazorla; Esperanza López-Rubio; Ana Romera; Sergio Barroso; Ana Huerta; Leonardo Calle; Milagros Sierra; Patricia Domínguez-Torres; Manuela Moreno-Ramírez; Sara Afonso; Victoria Mascarós; Armando Coca; Mario Espinosa Journal: Front Med (Lausanne) Date: 2022-07-05