Effects of rituximab on resistant SLE disease including lung involvement
Identifieur interne : 001579 ( Istex/Corpus ); précédent : 001578; suivant : 001580Effects of rituximab on resistant SLE disease including lung involvement
Auteurs : Ja Reynolds ; V. Toescu ; Cs Yee ; A. Prabu ; D. Situnayake ; C. GordonSource :
- Lupus [ 0961-2033 ] ; 2009-01.
English descriptors
- Teeft :
- Antibody titres, Arthritis, Arthritis rheum, Baseline, Bilag, Bilag index, Bilag score, British isles lupus assessment group, Cardiorespiratory disease, Cell depletion, Classic british isles lupus assessment group, Clinical remission, Clinical response, Complement levels, Cyclophosphamide, Disease activity, Disease duration, Disease flare, Disease progression, Disease remission, Erythematosus, First treatment, Flare, Flow cytometry, Global bilag index score, Haem, Immunol, Immunosuppressant, Infusion, Intravenous cyclophosphamide, Lung disease, Lung function, Lupus, Lupus effects, Lupus erythematosus, Major flare, Malar rash, Median, Median disease duration, Median reduction, Median time, Minor flares, Mycophenolate, Mycophenolate mofetil, Neurological disease, Ohchq, Oral ulcers, Other immunosuppressants, Pericardial pain, Peripheral neuropathy, Renal, Respiratory function, Responder, Rheum, Rheumatology, Rituximab, Rituximab failure, Rituximab therapy, Rituximab treatment, Scores bilag score, Serum complement, Severe cardiorespiratory disease, Severe lung disease, Statistical significance, Steroid, Steroid dose, Steroid reduction, Steroid requirement, Subsequent period, Systemic lupus erythematosus, Transverse myelitis, Treatment protocols, Vital capacity.
Abstract
We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. Rituximab appeared to stabilise and possibly improve progressive lung disease.
Url:
DOI: 10.1177/0961203308094653
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ISTEX:7330775266A8E654EB5817985D5CB3F057403FA8Le document en format XML
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Toescu</name><affiliation><mods:affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</mods:affiliation></affiliation></author><author wicri:is="90%"><name sortKey="Yee, Cs" sort="Yee, Cs" uniqKey="Yee C" first="Cs" last="Yee">Cs Yee</name><affiliation><mods:affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</mods:affiliation></affiliation></author><author wicri:is="90%"><name sortKey="Prabu, A" sort="Prabu, A" uniqKey="Prabu A" first="A" last="Prabu">A. Prabu</name><affiliation><mods:affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</mods:affiliation></affiliation></author><author wicri:is="90%"><name sortKey="Situnayake, D" sort="Situnayake, D" uniqKey="Situnayake D" first="D" last="Situnayake">D. Situnayake</name><affiliation><mods:affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</mods:affiliation></affiliation></author><author wicri:is="90%"><name sortKey="Gordon, C" sort="Gordon, C" uniqKey="Gordon C" first="C" last="Gordon">C. Gordon</name><affiliation><mods:affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Lupus</title><idno type="ISSN">0961-2033</idno><idno type="eISSN">1477-0962</idno><imprint><publisher>SAGE Publications</publisher><pubPlace>Sage UK: London, England</pubPlace><date type="published" when="2009-01">2009-01</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="67">67</biblScope><biblScope unit="page" to="73">73</biblScope></imprint><idno type="ISSN">0961-2033</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0961-2033</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Antibody titres</term><term>Arthritis</term><term>Arthritis rheum</term><term>Baseline</term><term>Bilag</term><term>Bilag index</term><term>Bilag score</term><term>British isles lupus assessment group</term><term>Cardiorespiratory disease</term><term>Cell depletion</term><term>Classic british isles lupus assessment group</term><term>Clinical remission</term><term>Clinical response</term><term>Complement levels</term><term>Cyclophosphamide</term><term>Disease activity</term><term>Disease duration</term><term>Disease flare</term><term>Disease progression</term><term>Disease remission</term><term>Erythematosus</term><term>First treatment</term><term>Flare</term><term>Flow cytometry</term><term>Global bilag index score</term><term>Haem</term><term>Immunol</term><term>Immunosuppressant</term><term>Infusion</term><term>Intravenous cyclophosphamide</term><term>Lung disease</term><term>Lung function</term><term>Lupus</term><term>Lupus effects</term><term>Lupus erythematosus</term><term>Major flare</term><term>Malar rash</term><term>Median</term><term>Median disease duration</term><term>Median reduction</term><term>Median time</term><term>Minor flares</term><term>Mycophenolate</term><term>Mycophenolate mofetil</term><term>Neurological disease</term><term>Ohchq</term><term>Oral ulcers</term><term>Other immunosuppressants</term><term>Pericardial pain</term><term>Peripheral neuropathy</term><term>Renal</term><term>Respiratory function</term><term>Responder</term><term>Rheum</term><term>Rheumatology</term><term>Rituximab</term><term>Rituximab failure</term><term>Rituximab therapy</term><term>Rituximab treatment</term><term>Scores bilag score</term><term>Serum complement</term><term>Severe cardiorespiratory disease</term><term>Severe lung disease</term><term>Statistical significance</term><term>Steroid</term><term>Steroid dose</term><term>Steroid reduction</term><term>Steroid requirement</term><term>Subsequent period</term><term>Systemic lupus erythematosus</term><term>Transverse myelitis</term><term>Treatment protocols</term><term>Vital capacity</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. 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Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</json:string></affiliations></json:item><json:item><name>CS Yee</name><affiliations><json:string>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</json:string></affiliations></json:item><json:item><name>A Prabu</name><affiliations><json:string>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</json:string></affiliations></json:item><json:item><name>D Situnayake</name><affiliations><json:string>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</json:string></affiliations></json:item><json:item><name>C Gordon</name><affiliations><json:string>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; 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We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. 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vascularites</json:string></inist></categories><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1177/0961203308094653</json:string></doi><id>7330775266A8E654EB5817985D5CB3F057403FA8</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/M70-RC6K7X0K-W/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/M70-RC6K7X0K-W/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/M70-RC6K7X0K-W/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Effects of rituximab on resistant SLE disease including lung involvement</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">SAGE Publications</publisher><pubPlace>Sage UK: London, England</pubPlace><availability><licence><p>sage</p></licence></availability><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-0J1N7DQT-B"></p><date>2009</date></publicationStmt><notesStmt><note type="other" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-7474895G-0">other</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Effects of rituximab on resistant SLE disease including lung involvement</title><author xml:id="author-0000"><persName><forename type="first">JA</forename><surname>Reynolds</surname></persName><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</affiliation></author><author xml:id="author-0001"><persName><forename type="first">V</forename><surname>Toescu</surname></persName><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></author><author xml:id="author-0002"><persName><forename type="first">CS</forename><surname>Yee</surname></persName><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></author><author xml:id="author-0003"><persName><forename type="first">A</forename><surname>Prabu</surname></persName><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></author><author xml:id="author-0004"><persName><forename type="first">D</forename><surname>Situnayake</surname></persName><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</affiliation></author><author xml:id="author-0005"><persName><forename type="first">C</forename><surname>Gordon</surname></persName><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></author><idno type="istex">7330775266A8E654EB5817985D5CB3F057403FA8</idno><idno type="ark">ark:/67375/M70-RC6K7X0K-W</idno><idno type="DOI">10.1177/0961203308094653</idno><idno type="article-id">10.1177_0961203308094653</idno></analytic><monogr><title level="j">Lupus</title><idno type="pISSN">0961-2033</idno><idno type="eISSN">1477-0962</idno><idno type="publisher-id">LUP</idno><idno type="PublisherID-hwp">splup</idno><imprint><publisher>SAGE Publications</publisher><pubPlace>Sage UK: London, England</pubPlace><date type="published" when="2009-01"></date><biblScope unit="volume">18</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="67">67</biblScope><biblScope unit="page" to="73">73</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. Rituximab appeared to stabilise and possibly improve progressive lung disease.</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>B cells</term></item><item><term>lung disease</term></item><item><term>rituximab</term></item><item><term>SLE</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/M70-RC6K7X0K-W/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus sage not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="other" dtd-version="2.3" xml:lang="EN"><front><journal-meta><journal-id journal-id-type="hwp">splup</journal-id><journal-id journal-id-type="publisher-id">LUP</journal-id><journal-title>Lupus</journal-title><issn pub-type="ppub">0961-2033</issn><publisher><publisher-name>SAGE Publications</publisher-name><publisher-loc>Sage UK: London, England</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.1177/0961203308094653</article-id><article-id pub-id-type="publisher-id">10.1177_0961203308094653</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Effects of rituximab on resistant SLE disease including lung involvement</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Reynolds</surname><given-names>JA</given-names></name><aff>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</aff></contrib></contrib-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Toescu</surname><given-names>V</given-names></name><aff>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</aff></contrib></contrib-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Yee</surname><given-names>CS</given-names></name><aff>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</aff></contrib></contrib-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Prabu</surname><given-names>A</given-names></name><aff>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</aff></contrib></contrib-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Situnayake</surname><given-names>D</given-names></name><aff>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</aff></contrib></contrib-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gordon</surname><given-names>C</given-names></name><aff>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</aff></contrib></contrib-group><pub-date pub-type="ppub"><month>01</month><year>2009</year></pub-date><volume>18</volume><issue>1</issue><fpage>67</fpage><lpage>73</lpage><abstract><p>We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (<italic>P</italic> = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 <italic>P</italic> = 0.008, C4 <italic>P</italic> = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (<italic>P</italic> = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. Rituximab appeared to stabilise and possibly improve progressive lung disease.</p></abstract><kwd-group><kwd>B cells</kwd><kwd>lung disease</kwd><kwd>rituximab</kwd><kwd>SLE</kwd></kwd-group><custom-meta-wrap><custom-meta xlink:type="simple"><meta-name>sagemeta-type</meta-name><meta-value>brief-report</meta-value></custom-meta><custom-meta xlink:type="simple"><meta-name>search-text</meta-name><meta-value>lupLupus0961-203310.1177/096120330809465308094653Concise ReportEffects of rituximab on resistant SLE disease including lung involvementEffects of rituximab on resistant SLE diseaseReynoldsJA1ToescuV12YeeCS12PrabuA12SitunayakeD1GordonCProfessor121Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK2Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UKCorrespondence to: Caroline Gordon (Professor), Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, B15 2TT, UK. Email: p.c.gordon@bham.ac.uk01002009181677351120072552008SAGE Publications2008We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. Rituximab appeared to stabilise and possibly improve progressive lung disease.Key wordsB cellslung diseaserituximabSLEIntroductionSystemic lupus erythematosus (SLE) is a multi-system, inflammatory, autoimmune disorder characterised by the formation of anti-nuclear antibodies. The clinical manifestations of lupus range from mild symptoms to life-threatening multi-organ failure.1 SLE is responsible for considerable morbidity and premature death in these patients.2Conventional treatment for SLE currently comprises a combination of corticosteroids and immunosuppressants, augmented by antimalarial agents. Although many patients can be well controlled with low-dose steroids and milder agents alone, a significant number requires increasingly potent agents in order to induce and maintain clinical remission. Although newer agents, such as mycophenolate mofetil, offer some hope to those who do not respond well to cyclophosphamide, a number of patients continue to suffer devastating disease.Lupus is primarily a disease of B-cell origin.3 The B cell is involved in the development of the autoimmune state, in the proliferation and progress of the immune response and directly in tissue inflammation.4 Inhibiting or removing autoreactive B cells while leaving the rest of the immune system intact offers an attractive potential treatment strategy. Rituximab is a chimeric mouse-human monoclonal antibody directed against the CD20 found on all human B cells with the exception of very early (B-cell progenitor) and terminally differentiated (plasma) cells.5 CD20 provides an ideal target as it is neither internalised nor soluble, has no known natural ligand or analogue, and anti-CD20 immunoglobulin initiates B-cell death.6To date, no randomised control trials of rituximab in lupus have been published although multiple case reports and small open-label studies described the clinical benefit of B-cell depletion. The largest open study of 24 patients with SLE (mean follow-up of 23 months) showed reduced disease activity, normalisation of complement and reduced steroid requirement in patients unresponsive to conventional immunosuppressants.7 The majority of these patients had lupus nephritis and had been treated with azathioprine and cyclophosphamide. Neuropsychiatric manifestations of lupus, predominantly acute confusional state and mood disorder also responded rapidly to rituximab.8In this study, we report our experience of rituximab in patients with less common features of lupus including those with neurological (transverse myelitis, peripheral neuropathy, seizures, psychosis) and severe cardiorespiratory disease (interstitial fibrosis, pericardial pain).MethodologyWe identified 11 patients treated with rituximab, under regular follow-up in dedicated lupus clinics in Birmingham. Nine patients met the revised American College of Rheumatology (ACR) classification criteria for SLE.9 Two patients only satisfied three criteria. All the patients had a clinical diagnosis of lupus that was confirmed by a rheumatologist. Disease duration was defined as the period of time from development of the fourth (or third in those with less than four) criteria. All patients were treated with rituximab according to clinical need after failing to respond to one or more conventional immunosuppressants. All patients provided written consent to take part in a study with approval from the local research ethics committee.Eight patients were treated with standardised doses of either 750 mg or 1 g of rituximab on two occasions, 2 weeks apart.7 Seven patients had concomitant intravenous cyclophosphamide (500–750 mg), and six patients had intravenous methylprednisolone (250–500 mg). Two patients were treated according to local protocols for treatment of B-cell lymphoma with two rituximab infusions of 375 mg/m2 with no concomitant cyclophosphamide,10 and one patient received two infusions of 500 mg rituximab with 750 mg cyclophosphamide. Following treatment, patients were allowed to continue with hydroxychloroquine and prednisolone.Disease activity was measured at routine follow-up clinic appointments using the Classic British Isles Lupus Assessment Group (BILAG) index.11 Global BILAG score was calculated by attributing numerical scores correlating to the categorical score for each individual system (A = 9, B = 3, C = 1, D/E = 0), which was then summated.7 Reduction in global BILAG score and loss of individual A or B scores provided objective assessment of disease response to treatment. A flare of disease was defined as a major (new A) or minor (new B) flare.12The B lymphocyte count following rituximab was measured using flow cytometry. B-cell recovery was defined as a B-cell count ≥0.01 × 109/L. We aimed to measure B cells every 4 weeks following rituximab although this was not always possible due to patients not attending appointments and other practical problems. Disease biomarkers especially anti-dsDNA antibody titres and serum complement were measured routinely at follow-up clinic visits. When there was no 6 months sample available, the next sample taken was used. All pulmonary function measurements were performed according to Association for Respiratory Technology and Physiology/British Thoracic Society (ATRP/BTS) guidelines for the measurement of respiratory function13 and were requested on clinical grounds.Data were analysed using the Wilcoxon signed-rank test for non-parametric paired data.ResultsBaseline characteristicsWe identified 11 lupus patients who had been treated with rituximab. In all, 9 of 11 patients fulfilled four ACR criteria and the remaining two patients fulfilled three. All 11 patients were positive for ANA. The demographic variables are summarised in Table 1. The mean patient age was 42 years (range, 25–64), and median disease duration was 6 years (range, 2–16).Table 1Profile of the 11 patientsPatientSexAgeEthnic originACR criteria9Disease duration (y)SLICC/ACR damage index1F30South AsianArthritis, haem, immunol, ANA212F47Afro-CaribbeanOral ulcers, arthritis, serositis, renal, haem, immunol, ANA1613F29CaucasianPhotosensitivity, oral ulcers, arthritis, serositis, neuro, haem, ANA904F32Afro-CaribbeanMalar rash, oral ulcers, arthritis, renal, neuro, haem, immunol, ANA705F25Afro-CaribbeanMalar rash, oral ulcers, arthritis, renal, haem, immunol, ANA406F42Afro-CaribbeanArthritis, haem, ANA627M46CaucasianRenal, neuro, haem, immunol, ANA1158M58CaucasianPhotosensitivity, serositis, immunol, ANA619F64CaucasianPhotosensitivity, arthritis, ANA4110F54South AsianMalar rash, discoid rash, arthritis, renal, haem, immunol, ANA14011F36South AsianMalar rash, oral ulcers, arthritis, immunol, ANA61Abbreviations: M: male; F: female; SLICC: Systemic Lupus International Collaborating Clinics.Disease duration calculated from time of onset of the fourth ACR criteria9 (or third if </meta-value> </custom-meta></custom-meta-wrap></article-meta></front><back><ref-list><ref><citation citation-type="journal" xlink:type="simple">1 <name name-style="western"><surname>D’Cruz DP </surname></name>. <article-title>Systemic lupus erythematosus</article-title>. <source>BMJ</source>
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<year>2007</year>; <volume>119</volume>: <fpage>S260</fpage> [Abstract].</citation></ref></ref-list></back></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Effects of rituximab on resistant SLE disease including lung involvement</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Effects of rituximab on resistant SLE disease including lung involvement</title></titleInfo><name type="personal"><namePart type="given">JA</namePart><namePart type="family">Reynolds</namePart><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</affiliation></name><name type="personal"><namePart type="given">V</namePart><namePart type="family">Toescu</namePart><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></name><name type="personal"><namePart type="given">CS</namePart><namePart type="family">Yee</namePart><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Prabu</namePart><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Situnayake</namePart><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK</affiliation></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Gordon</namePart><affiliation>Department of Rheumatology, City Hospital, Birmingham, West Midlands, UK; Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK</affiliation></name><typeOfResource>text</typeOfResource><genre type="other" displayLabel="other" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-7474895G-0">other</genre><originInfo><publisher>SAGE Publications</publisher><place><placeTerm type="text">Sage UK: London, England</placeTerm></place><dateIssued encoding="w3cdtf">2009-01</dateIssued><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months (P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day (P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. Rituximab appeared to stabilise and possibly improve progressive lung disease.</abstract><subject><genre>keywords</genre><topic>B cells</topic><topic>lung disease</topic><topic>rituximab</topic><topic>SLE</topic></subject><relatedItem type="host"><titleInfo><title>Lupus</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0961-2033</identifier><identifier type="eISSN">1477-0962</identifier><identifier type="PublisherID">LUP</identifier><identifier type="PublisherID-hwp">splup</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>18</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>67</start><end>73</end></extent></part></relatedItem><identifier type="istex">7330775266A8E654EB5817985D5CB3F057403FA8</identifier><identifier type="ark">ark:/67375/M70-RC6K7X0K-W</identifier><identifier type="DOI">10.1177/0961203308094653</identifier><identifier type="ArticleID">10.1177_0961203308094653</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-0J1N7DQT-B">sage</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/M70-RC6K7X0K-W/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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