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Rituximab in Severe Lupus Nephritis: Early B-Cell Depletion Affects Long-Term Renal Outcome

Catherine Melander^*, Marion Sallée^*, Pierre Trolliet, Sophie Candon, Xavier Belenfant, Eric Daugas^||, Phillipe Rémy^¶, Virginie Zarrouk^**, Evangéline Pillebout, Christian Jacquot, Jean-Jacques Boffa, Alexandre Karras, Virginie Masse^||||, Philippe Lesavre^*, Caroline Elie^||||, Isabelle Brocheriou^¶¶, Bertrand Knebelmann^*, Laure-Hélène Noël^***, and Fadi Fakhouri^*

^* Department of Nephrology, Assistance Publique—Hôpitaux Paris (AP-HP), Université Paris Descartes, Hôpital Necker, Paris, France; Department of Nephrology, Centre Hospitalier Lyon-Sud, Lyon, France; Department of Immunology, AP-HP, Hôpital Necker, Paris, France; Department of Nephrology, Centre Hospitalier Intercommunal André Grégoire, Montreuil, France; ^|| Department of Nephrology, AP-HP, Hôpital Bichat, Paris, France; ^¶ Department of Nephrology, AP-HP, Hôpital Henri Mondor, Créteil, France; ^** Department of Internal Medicine, AP-HP, Hôpital Beaujon, Clichy, France; Department of Nephrology, AP-HP, Hôpital Saint-Louis, Paris, France; Department of Nephrology, AP-HP, Hôpital Européen Georges Pompidou, Paris, France; Department of Nephrology, AP-HP, Hôpital Tenon, Paris, France; ^|||| Department of Biostatistics, AP-HP, Université Paris Descartes, Hôpital Necker, Paris, France; ^¶¶ Department of Pathology, AP-HP, Hôpital Pitié-Salpétrière, Paris, France; ^*** Department of Pathology, AP-HP, Hôpital Necker, Paris, France

Correspondence: Dr. Fadi Fakhouri, Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial College, Hammersmith Campus, London, United Kingdom. Phone: 00442083832379; Fax: 00442083832379; E-mail: f.fakhouri{at}imperial.ac.uk

Background and objectives: Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up.

Design, setting, participants, & measurements: The authors analyzed clinical and histologic data of 20 patients who were treated with rituximab for lupus nephritis and followed up for at least 12 mo.

Results: Nineteen women and one man received rituximab as induction treatment for an active class IV (15 cases) or class V (5 cases) lupus nephritis. Rituximab was given for lupus nephritis refractory to standard treatment (12 cases), for relapsing disease (6 cases), or as first-line treatment (2 cases). Three patients received cyclophosphamide concomitantly with rituximab. Ten received new injections of rituximab as maintenance therapy. Side effects included mainly five infections and four moderate neutropenias. After a median follow-up of 22 mo, complete or partial renal remission was obtained in 12 patients (60%). Lupus nephritis relapsed in one patient, who responded to a new course of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ethnicity and hypoalbuminemia, was strongly associated with renal response. Rapidly progressive glomerulonephritis did not respond to rituximab.

Conclusion: Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B cell depletion is obtained.

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