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.

Dr. Pagnoux, et al reply

“…In our experience and as reported by Aries et al 8 it should be noted that the therapeutic response to rituximab for this specific manifestation may be quite long in coming, compared to responses of some other manifestations, like arthritis, pauci-immune glomerulonephritis, or alveolar hemorrhage 9 . Optimal management of these rare but severe and challenging patients with subglottic and/or bronchial stenoses must be multidisciplinary, with ENT specialists and/or respirologists for local followup and therapy, and rheumatologists and/or internists to handle conventional systemic treatments, knowing their relatively limited, transient and/or partial efficacies, especially when subglottic stenosis is due to fibrosis.…”

Rituximab as a new therapeutic option in granulomatosis with polyangiitis: a report of two cases

“…Effect of cyclophosphamide on lymphocytes is, in fact, a major determinant for its treatment efficacy. The proportion of activated peripheral B lymphocytes is closely linked with disease activity in ANCA-associated vasculitides [9,10]. Rituximab is a chimeric monoclonal anti-CD20 antibody causing B-cell depletion.…”

Indications of Rituximab in autoimmune diseases

“…Nevertheless, these studies dovetailed nicely with strong experimental evidence indicating a pathogenic role of ANCA autoantibodies and opened the door to large, randomized controlled studies currently underway (RITUXVAS and RAVE). Meanwhile, several subsequent reports appear to substantiate the potential benefit of rituximab at least for the systemic, inflammatory component of the disease process 31. This potential has been perhaps best summarized by a recent retrospective analysis of a multicenter cohort of 65 patients treated with Rituximab for refractory AMV.…”