Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis

Vos, Koen; Thurlings, Rogier M.; Wijbrandts, Carla A.; Schaardenburg, Dirkjan van; Gerlag, Daniëlle M.; Tak, Paul P.

doi:10.1002/art.22400

Cited by 168 publications

(138 citation statements)

References 57 publications

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“…120 In other studies rituximab induced a similar variable depletion in synovial B cells with an indirect decrease in macrophages, T cells and plasma cells at the time of the clinical response. 121,122 Of interest, the change in plasma cells was associated with the clinical response.…”

Section: Cellular Compositionmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis (RA). The study of synovial tissue has advanced significantly over a number of decades from arthroplasty, blind needle biopsy and more recently facilitated by arthroscopic and ultrasonographic technology that allows easier visualisation and improves the reliability of obtaining synovial biopsies. The potential for study of pathogenesis, patient stratification, discovery of biomarkers and novel targets, as well as validation of therapy, have all been progressed rapidly in the last decade, facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this review we describe clinical and translational developments in the field of synovial tissue research, outlining current and novel investigative technologies, and highlight their application to advance our understanding of the aforegoing imperatives.3

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Section: Cellular Compositionmentioning

confidence: 99%

Synovial tissue research: a state-of-the-art review

et al. 2017

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“…A more sensitive analytical method may have shown closer correlations with disease activity. In addition, rituximab results in the reduction of CD20-positive B cells in tissues as well as in blood (36,37), which may not be complete in tissues (38,39). Certainly, tissue B cell repopulation can occur prior to detectable return to the peripheral blood (20).…”

Section: Discussionmentioning

confidence: 99%

A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis

Jones¹,

Ferraro²,

Chaudhry³

et al. 2009

Arthritis & Rheumatism

326

214

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Objective. B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as retreatment biomarkers.Methods. Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used.Results. All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P ‫؍‬ 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m 2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received >2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of lateonset neutropenia, which were attributed to rituximab.Conclusion. Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment.

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“…Although the exact mechanism of action of rituximab in RA is still not clear, synovial biopsy studies in RA patients after rituximab treatment show, in addition to changes in synovial B cell composition, changing synovial histology with slow loss of infiltrating macrophages and regressing inflammatory infiltrates (41,42). B cell trafficking between RA lesions and secondary lymphoid organs is thought to be intrin-sically involved in the pathophysiology of RA (43,44).…”

Section: Discussionmentioning

confidence: 99%