title: Analysis of Wegener's granulomatosis responses to rituximab: current evidence and therapeutic prospects.
abstract: Available data on small numbers of patients with refractory and/or relapsing Wegener's granulomatosis support very good overall outcomes with rituximab, an anti-CD20 biotherapy targeting B cells, in combination with ongoing immunosuppressants, apparently independently of antineutrophil cytoplasm antibody (ANCA) status. However, clearly dissociated responses were observed, with constitutional and vasculitis-related symptoms often achieving complete responses within days or weeks, and granulomatous-related manifestations regressing more slowly over a few weeks to several months or not at all, particularly for orbital pseudotumors. Tolerance was good with few side effects, and when relapses occurred, more often after 12 months, a second or even a third rituximab cycle was almost always able to obtain another complete remission. Randomized trials are needed to define rituximab's best place, compared to cyclophosphamide, in initial and maintenance regimens; to determine optimally combined drugs, considering the various responses of granulomatous-related manifestations; and to delineate the role of circulating B-cell monitoring for pre-emptive management decisions. This promising biotherapy opens the way for other therapeutic agents targeting B lymphocytes and to improve our understanding of the pathophysiology of ANCA-associated vasculitis.
authors.affiliation: Department of Internal Medicine and the French Vasculitis Study Group, Assistance Publique-Hôpitaux de Paris, Université Paris, 5-René-Descartes, Hôpital Cochin, 27, rue du faubourg Saint-Jacques, 75679, Paris Cedex 14, France. achille.aouba@wanadoo.fr
authors.forename: Achille
authors.initials: A
authors.lastname: Aouba
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
authors.forename: Boris
authors.initials: B
authors.lastname: Bienvenu
authors.forename: Alfred
authors.initials: A
authors.lastname: Mahr
authors.forename: Loïc
authors.initials: L
authors.lastname: Guillevin
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab