Methotrexate: long‐term safety and efficacy in an Australian consultant rheumatology practice
Identifieur interne : 001340 ( Istex/Corpus ); précédent : 001339; suivant : 001341Methotrexate: long‐term safety and efficacy in an Australian consultant rheumatology practice
Auteurs : N. Varatharajan ; I. G. S. Lim ; A. Anandacoomarasamy ; R. Russo ; K. Byth ; D. G. Spencer ; N. Manolios ; G. B. HoweSource :
- Internal Medicine Journal [ 1444-0903 ] ; 2009-04.
English descriptors
- Teeft :
- Adverse reaction, Adverse reactions, Arthritis, Arthritis rheum, Australasian, Authors journal compilation, Average duration, Biopsy, Blood monitoring, Cessation, Clinical impression, Clinical practice, Combination therapy, Common reason, Complete remission, Complete remission group, Current monitoring guidelines, Discontinuation rates, Effective medication, Females males, Folic, Folic acid, Gastrointestinal symptoms, Guideline, Hazard ratios, Median, Median duration, Median number, Median time, Methotrexate, Monitoring guidelines, Multiple sclerosis, Other causes, Other reasons, Physicians methotrexate outcomes table, Primary biliary cirrhosis, Primary outcome, Private practice, Range years, Remission, Remission status, Renal failure, Rheum, Rheumatoid, Rheumatoid arthritis, Rheumatology, Royal australasian college, Seronegative, Seronegative arthritis, Survival curves, Systemic lupus erythematosus, Tight control, Toxicity, Various subgroups, Vasculitis, Weekly dose, Western sydney, Westmead hospital.
Abstract
Background: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. Methods: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18‐year period. The primary outcome was time to cessation of MTX. Results: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity‐related discontinuation occurred in 93 patients (11.8%) and due to non‐adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non‐RA diagnosis predisposed to stopping MTX earlier. Conclusion: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re‐evaluate and revise the current monitoring guidelines.
Url:
DOI: 10.1111/j.1445-5994.2009.01800.x
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ISTEX:DF968489323B8F50B2C2CE2BC06D1B88F325FBCELe document en format XML
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Methods: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18‐year period. The primary outcome was time to cessation of MTX. Results: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity‐related discontinuation occurred in 93 patients (11.8%) and due to non‐adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non‐RA diagnosis predisposed to stopping MTX earlier. Conclusion: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. 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Varatharajan</name><affiliations><json:string>Western Sydney Clinical School, University of Sydney,</json:string></affiliations></json:item><json:item><name>I. G. S. Lim</name><affiliations><json:string>Department of Rheumatology and</json:string></affiliations></json:item><json:item><name>A. Anandacoomarasamy</name><affiliations><json:string>Department of Rheumatology and</json:string></affiliations></json:item><json:item><name>R. Russo</name><affiliations><json:string>Department of Rheumatology and</json:string></affiliations></json:item><json:item><name>K. Byth</name><affiliations><json:string>Westmead Millennium Institute, Sydney, New South Wales, Australia</json:string></affiliations></json:item><json:item><name>D. G. Spencer</name><affiliations><json:string>Department of Rheumatology and</json:string></affiliations></json:item><json:item><name>N. Manolios</name><affiliations><json:string>Department of Rheumatology and</json:string></affiliations></json:item><json:item><name>G. B. Howe</name><affiliations><json:string>Department of Rheumatology and</json:string><json:string>E-mail: ghowe@staff.usyd.edu.au</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>methotrexate</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>adverse reaction</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>monitoring guideline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>rheumatoid arthritis</value></json:item></subject><articleId><json:string>IMJ1800</json:string></articleId><arkIstex>ark:/67375/WNG-F6S7ZLCV-C</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Background: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. Methods: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18‐year period. The primary outcome was time to cessation of MTX. Results: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity‐related discontinuation occurred in 93 patients (11.8%) and due to non‐adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; P > 0.001). Being of the male sex aged more than 60 years and having a non‐RA diagnosis predisposed to stopping MTX earlier. Conclusion: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. 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G.</forename><surname>Spencer</surname></persName><affiliation><orgName type="division">Department of Rheumatology and</orgName></affiliation></author><author xml:id="author-0006"><persName><forename type="first">N.</forename><surname>Manolios</surname></persName><affiliation><orgName type="division">Department of Rheumatology and</orgName></affiliation></author><author xml:id="author-0007" role="corresp"><persName><forename type="first">G. B.</forename><surname>Howe</surname></persName><affiliation><orgName type="division">Department of Rheumatology and</orgName></affiliation></author><idno type="istex">DF968489323B8F50B2C2CE2BC06D1B88F325FBCE</idno><idno type="ark">ark:/67375/WNG-F6S7ZLCV-C</idno><idno type="DOI">10.1111/j.1445-5994.2009.01800.x</idno><idno type="unit">IMJ1800</idno><idno type="toTypesetVersion">file:IMJ.IMJ1800.pdf</idno></analytic><monogr><title level="j" type="main">Internal Medicine Journal</title><title level="j" type="alt">INTERNAL MEDICINE JOURNAL</title><idno type="pISSN">1444-0903</idno><idno type="eISSN">1445-5994</idno><idno type="book-DOI">10.1111/(ISSN)1445-5994</idno><idno type="book-part-DOI">10.1111/imj.2009.39.issue-4</idno><idno type="product">IMJ</idno><idno type="publisherDivision">ST</idno><imprint><biblScope unit="vol">39</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="228">228</biblScope><biblScope unit="page" to="236">236</biblScope><biblScope unit="page-count">9</biblScope><publisher>Blackwell Publishing Asia</publisher><pubPlace>Melbourne, Australia</pubPlace><date type="published" when="2009-04"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef><appInfo><application ident="pub2tei" version="1.0.10" when="2019-12-20"><label>pub2TEI-ISTEX</label><desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p><hi rend="bold">Background:</hi> The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment.</p><p><hi rend="bold">Methods:</hi> A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18‐year period. The primary outcome was time to cessation of MTX.</p><p><hi rend="bold">Results:</hi> Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity‐related discontinuation occurred in 93 patients (11.8%) and due to non‐adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; <hi rend="italic">P</hi> = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; <hi rend="italic">P</hi> < 0.001). Being of the male sex aged more than 60 years and having a non‐RA diagnosis predisposed to stopping MTX earlier.</p><p><hi rend="bold">Conclusion:</hi> MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re‐evaluate and revise the current monitoring guidelines.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="k1">methotrexate</term><term xml:id="k2">adverse reaction</term><term xml:id="k3">monitoring guideline</term><term xml:id="k4">rheumatoid arthritis</term></keywords><keywords rend="tocHeading1"><term>Original Articles</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-20" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/WNG-F6S7ZLCV-C/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Asia</publisherName><publisherLoc>Melbourne, Australia</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1445-5994</doi><issn type="print">1444-0903</issn><issn type="electronic">1445-5994</issn><idGroup><id type="product" value="IMJ"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="INTERNAL MEDICINE JOURNAL">Internal Medicine Journal</title></titleGroup></publicationMeta><publicationMeta level="part" position="04004"><doi origin="wiley">10.1111/imj.2009.39.issue-4</doi><numberingGroup><numbering type="journalVolume" number="39">39</numbering><numbering type="journalIssue" number="4">4</numbering></numberingGroup><coverDate startDate="2009-04">April 2009</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="4" status="forIssue"><doi origin="wiley">10.1111/j.1445-5994.2009.01800.x</doi><idGroup><id type="unit" value="IMJ1800"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="tocHeading1">Original Articles</title></titleGroup><copyright>© 2009 The Authors. Journal compilation © 2009 Royal Australasian College of Physicians</copyright><eventGroup><event type="firstOnline" date="2009-04-21"></event><event type="publishedOnlineFinalForm" date="2009-04-21"></event><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.3.5 mode:FullText source:FullText result:FullText" date="2010-04-07"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-01-28"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-24"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="228">228</numbering><numbering type="pageLast" number="236">236</numbering></numberingGroup><correspondenceTo>Graydon B. Howe, Suite 203, Specialist Medical Centre, 151–155 Hawkesbury Road, Westmead, NSW 2145, Australia.
Email: <email>ghowe@staff.usyd.edu.au</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:IMJ.IMJ1800.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 2 November 2007; accepted 27 July 2008.</unparsedEditorialHistory><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="7"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="21"></count><count type="wordTotal" number="5423"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">Methotrexate: long‐term safety and efficacy in an Australian consultant rheumatology practice</title><title type="shortAuthors">Varatharajan <i>et al.</i></title><title type="short">Methotrexate outcomes</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1"><personName><givenNames>N.</givenNames><familyName>Varatharajan</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a2"><personName><givenNames>I. G. S.</givenNames><familyName>Lim</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a2"><personName><givenNames>A.</givenNames><familyName>Anandacoomarasamy</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a2"><personName><givenNames>R.</givenNames><familyName>Russo</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a3"><personName><givenNames>K.</givenNames><familyName>Byth</familyName></personName></creator><creator creatorRole="author" xml:id="cr6" affiliationRef="#a2"><personName><givenNames>D. G.</givenNames><familyName>Spencer</familyName></personName></creator><creator creatorRole="author" xml:id="cr7" affiliationRef="#a2"><personName><givenNames>N.</givenNames><familyName>Manolios</familyName></personName></creator><creator creatorRole="author" xml:id="cr8" affiliationRef="#a2" corresponding="yes"><personName><givenNames>G. B.</givenNames><familyName>Howe</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1"><unparsedAffiliation>Western Sydney Clinical School, University of Sydney,</unparsedAffiliation></affiliation><affiliation xml:id="a2"><unparsedAffiliation>Department of Rheumatology and</unparsedAffiliation></affiliation><affiliation xml:id="a3" countryCode="AU"><unparsedAffiliation>Westmead Millennium Institute, Sydney, New South Wales, Australia</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">methotrexate</keyword><keyword xml:id="k2">adverse reaction</keyword><keyword xml:id="k3">monitoring guideline</keyword><keyword xml:id="k4">rheumatoid arthritis</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p><b>Background:</b> The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment.</p><p><b>Methods:</b> A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18‐year period. The primary outcome was time to cessation of MTX.</p><p><b>Results:</b> Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity‐related discontinuation occurred in 93 patients (11.8%) and due to non‐adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; <i>P</i> = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; <i>P</i> < 0.001). Being of the male sex aged more than 60 years and having a non‐RA diagnosis predisposed to stopping MTX earlier.</p><p><b>Conclusion:</b> MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re‐evaluate and revise the current monitoring guidelines.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1" numbered="no"><p>Funding: None</p></note><note xml:id="fn2" numbered="no"><p>Potential conflicts of interest: None</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Methotrexate: long‐term safety and efficacy in an Australian consultant rheumatology practice</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Methotrexate outcomes</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Methotrexate: long‐term safety and efficacy in an Australian consultant rheumatology practice</title></titleInfo><name type="personal"><namePart type="given">N.</namePart><namePart type="family">Varatharajan</namePart><affiliation>Western Sydney Clinical School, University of Sydney,</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">I. G. S.</namePart><namePart type="family">Lim</namePart><affiliation>Department of Rheumatology and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A.</namePart><namePart type="family">Anandacoomarasamy</namePart><affiliation>Department of Rheumatology and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Russo</namePart><affiliation>Department of Rheumatology and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">K.</namePart><namePart type="family">Byth</namePart><affiliation>Westmead Millennium Institute, Sydney, New South Wales, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D. G.</namePart><namePart type="family">Spencer</namePart><affiliation>Department of Rheumatology and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">N.</namePart><namePart type="family">Manolios</namePart><affiliation>Department of Rheumatology and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G. B.</namePart><namePart type="family">Howe</namePart><affiliation>Department of Rheumatology and</affiliation><affiliation>E-mail: ghowe@staff.usyd.edu.au</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Blackwell Publishing Asia</publisher><place><placeTerm type="text">Melbourne, Australia</placeTerm></place><dateIssued encoding="w3cdtf">2009-04</dateIssued><edition>Received 2 November 2007; accepted 27 July 2008.</edition><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">3</extent><extent unit="tables">7</extent><extent unit="formulas">0</extent><extent unit="references">21</extent><extent unit="linksCrossRef">0</extent><extent unit="words">5423</extent></physicalDescription><abstract lang="en">Background: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. Methods: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18‐year period. The primary outcome was time to cessation of MTX. Results: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity‐related discontinuation occurred in 93 patients (11.8%) and due to non‐adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57–0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42–0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non‐RA diagnosis predisposed to stopping MTX earlier. Conclusion: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re‐evaluate and revise the current monitoring guidelines.</abstract><subject lang="en"><genre>keywords</genre><topic>methotrexate</topic><topic>adverse reaction</topic><topic>monitoring guideline</topic><topic>rheumatoid arthritis</topic></subject><relatedItem type="host"><titleInfo><title>Internal Medicine Journal</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">1444-0903</identifier><identifier type="eISSN">1445-5994</identifier><identifier type="DOI">10.1111/(ISSN)1445-5994</identifier><identifier type="PublisherID">IMJ</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>39</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>228</start><end>236</end><total>9</total></extent></part></relatedItem><relatedItem type="references" displayLabel="cit1"><titleInfo><title>Therapeutic suppression of tissue reactivity. 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