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Pragmatic treatment of patients with Systemic Lupus Erythematosus with rituximab: Long-term effects on serum immunoglobulins

Reddy, V; Martinez, L; Isenberg, DA; Leandro, MJ; Cambridge, G; (2016) Pragmatic treatment of patients with Systemic Lupus Erythematosus with rituximab: Long-term effects on serum immunoglobulins. Arthritis Care Res (Hoboken) , 69 (6) pp. 857-866. 10.1002/acr.22993. Green open access

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Abstract

OBJECTIVE: B cell depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with Systemic Lupus Erythematosus (SLE). The aim of this observational study was to document long-term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice. METHODS: We included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti-dsDNA antibodies over a median of 48 months most recent follow-up. Flow cytometry was used prospectively to assess B-cell phenotypes in 17/57 patients. RESULTS: Twelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 g/L) and 3/55 (5%) had low IgG (<7g/L) at most recent follow-up (range 12-144 months). This was not associated with serious adverse events or high anti-dsDNA antibodies (>1000IU/ml; normal<50IU/ml). Factors predictive of low serum IgM included: baseline serum IgM ≤0.8g/L (receiver-operated-curve analysis) and subsequent therapy with mycophenolate mofetil (MMF) (odds ratio=6.8 compared with other immunosuppressants). In patients maintaining normal IgM levels (9/17), the frequency of circulating IgD+CD27+ B cells was significantly higher (p=0.05). At 12 months after rituximab, 7/30 SLE patients with baseline anti-dsDNA≤1000 IU/ml had lost seropositivity. CONCLUSIONS: Lower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti-dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE. This article is protected by copyright. All rights reserved.

Type: Article
Title: Pragmatic treatment of patients with Systemic Lupus Erythematosus with rituximab: Long-term effects on serum immunoglobulins
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acr.22993
Publisher version: http://dx.doi.org/10.1002/acr.22993
Language: English
Additional information: © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: B cell phenotypes, anti-dsDNA antibodies, mycophenolate mofetil, rituximab, serum immunoglobulins, systemic lupus erythematosus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1526827
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