Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis
Identifieur interne : 000692 ( Istex/Corpus ); précédent : 000691; suivant : 000693Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis
Auteurs : L. Cummins ; V. S. Katikireddi ; S. Shankaranarayana ; K. Y. C. Su ; E. Duggan ; V. Videm ; H. Pahau ; R. ThomasSource :
- Internal Medicine Journal [ 1444-0903 ] ; 2015-12.
Abstract
Background: While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (‘triple therapy’) has been shown in clinical trials, few studies have examined its longevity in a real‐life setting. Aim: Our aim was to assess the tolerability, longevity and efficacy of a triple disease‐modifying anti‐rheumatic drug (DMARD) regimen initiated in new‐onset rheumatoid arthritis (RA) patients. Methods: Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response‐driven step‐up algorithm, which included progression to leflunomide (LEF) or a biologic agent. Results: Of 181 new‐onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three‐DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three‐drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA). Conclusions: Triple therapy in new‐onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.
Url:
DOI: 10.1111/imj.12896
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Katikireddi</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Shankaranarayana, S" sort="Shankaranarayana, S" uniqKey="Shankaranarayana S" first="S." last="Shankaranarayana">S. Shankaranarayana</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Su, K Y C" sort="Su, K Y C" uniqKey="Su K" first="K. Y. C." last="Su">K. Y. C. Su</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Duggan, E" sort="Duggan, E" uniqKey="Duggan E" first="E." last="Duggan">E. 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Pahau</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Thomas, R" sort="Thomas, R" uniqKey="Thomas R" first="R." last="Thomas">R. Thomas</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Princess Alexandra Hospital, Queensland, Brisbane, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>CorrespondenceRanjeny Thomas, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Qld 4102, Australia.Email:</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ranjeny.thomas@uq.edu.au</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:29DBE3741864C51565F2C98CC77215329978D3AE</idno><date when="2015" year="2015">2015</date><idno type="doi">10.1111/imj.12896</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-BL4FV68G-Q/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000692</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000692</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis</title><author><name sortKey="Cummins, L" sort="Cummins, L" uniqKey="Cummins L" first="L." last="Cummins">L. Cummins</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Princess Alexandra Hospital, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Katikireddi, V S" sort="Katikireddi, V S" uniqKey="Katikireddi V" first="V. S." last="Katikireddi">V. S. Katikireddi</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Shankaranarayana, S" sort="Shankaranarayana, S" uniqKey="Shankaranarayana S" first="S." last="Shankaranarayana">S. Shankaranarayana</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Su, K Y C" sort="Su, K Y C" uniqKey="Su K" first="K. Y. C." last="Su">K. Y. C. Su</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Duggan, E" sort="Duggan, E" uniqKey="Duggan E" first="E." last="Duggan">E. Duggan</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Videm, V" sort="Videm, V" uniqKey="Videm V" first="V." last="Videm">V. Videm</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway</mods:affiliation></affiliation><affiliation><mods:affiliation>Department of Immunology and Transfusion Medicine, St Olav University Hospital, Trondheim, Norway</mods:affiliation></affiliation></author><author><name sortKey="Pahau, H" sort="Pahau, H" uniqKey="Pahau H" first="H." last="Pahau">H. Pahau</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</mods:affiliation></affiliation></author><author><name sortKey="Thomas, R" sort="Thomas, R" uniqKey="Thomas R" first="R." last="Thomas">R. Thomas</name><affiliation><mods:affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>Princess Alexandra Hospital, Queensland, Brisbane, Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>CorrespondenceRanjeny Thomas, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Qld 4102, Australia.Email:</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ranjeny.thomas@uq.edu.au</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Internal Medicine Journal</title><title level="j" type="alt">INTERNAL MEDICINE JOURNAL</title><idno type="ISSN">1444-0903</idno><idno type="eISSN">1445-5994</idno><imprint><biblScope unit="vol">45</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1266">1266</biblScope><biblScope unit="page" to="1273">1273</biblScope><biblScope unit="page-count">9</biblScope><date type="published" when="2015-12">2015-12</date></imprint><idno type="ISSN">1444-0903</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1444-0903</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background: While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (‘triple therapy’) has been shown in clinical trials, few studies have examined its longevity in a real‐life setting. Aim: Our aim was to assess the tolerability, longevity and efficacy of a triple disease‐modifying anti‐rheumatic drug (DMARD) regimen initiated in new‐onset rheumatoid arthritis (RA) patients. Methods: Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response‐driven step‐up algorithm, which included progression to leflunomide (LEF) or a biologic agent. Results: Of 181 new‐onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three‐DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three‐drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA). Conclusions: Triple therapy in new‐onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>L. Cummins</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</json:string><json:string>Princess Alexandra Hospital, Queensland, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>V. S. Katikireddi</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>S. Shankaranarayana</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>K. Y. C. Su</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>E. Duggan</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>V. Videm</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</json:string><json:string>Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway</json:string><json:string>Department of Immunology and Transfusion Medicine, St Olav University Hospital, Trondheim, Norway</json:string></affiliations></json:item><json:item><name>H. Pahau</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</json:string></affiliations></json:item><json:item><name>R. Thomas</name><affiliations><json:string>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</json:string><json:string>Princess Alexandra Hospital, Queensland, Brisbane, Australia</json:string><json:string>CorrespondenceRanjeny Thomas, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Qld 4102, Australia.Email:</json:string><json:string>E-mail: ranjeny.thomas@uq.edu.au</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>rheumatoid arthritis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>anti‐rheumatic agents</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>medication persistence</value></json:item></subject><articleId><json:string>IMJ12896</json:string></articleId><arkIstex>ark:/67375/WNG-BL4FV68G-Q</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>Background: While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (‘triple therapy’) has been shown in clinical trials, few studies have examined its longevity in a real‐life setting. Aim: Our aim was to assess the tolerability, longevity and efficacy of a triple disease‐modifying anti‐rheumatic drug (DMARD) regimen initiated in new‐onset rheumatoid arthritis (RA) patients. Methods: Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response‐driven step‐up algorithm, which included progression to leflunomide (LEF) or a biologic agent. Results: Of 181 new‐onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three‐DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three‐drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA). Conclusions: Triple therapy in new‐onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. 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S.</forename><surname>Katikireddi</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">S.</forename><surname>Shankaranarayana</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">K. Y. C.</forename><surname>Su</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">E.</forename><surname>Duggan</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">V.</forename><surname>Videm</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation><affiliation><orgName type="division">Department of Laboratory Medicine, Children's and Women's Health</orgName><orgName type="institution">Norwegian University of Science and Technology</orgName><address><settlement>Trondheim</settlement><country key="NO" xml:lang="en">NORWAY</country></address></affiliation><affiliation><orgName type="division">Department of Immunology and Transfusion Medicine</orgName><orgName type="institution">St Olav University Hospital</orgName><address><settlement>Trondheim</settlement><country key="NO" xml:lang="en">NORWAY</country></address></affiliation></author><author xml:id="author-0006"><persName><forename type="first">H.</forename><surname>Pahau</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation></author><author xml:id="author-0007" role="corresp"><persName><forename type="first">R.</forename><surname>Thomas</surname></persName><affiliation><orgName type="division">University of Queensland Diamantina Institute</orgName><orgName type="institution">Translational Research Institute</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation><affiliation><orgName type="institution">Princess Alexandra Hospital</orgName><address><settlement>Brisbane</settlement><region>Queensland</region><country key="AU" xml:lang="en">AUSTRALIA</country></address></affiliation></author><idno type="istex">29DBE3741864C51565F2C98CC77215329978D3AE</idno><idno type="ark">ark:/67375/WNG-BL4FV68G-Q</idno><idno type="DOI">10.1111/imj.12896</idno><idno type="unit">IMJ12896</idno><idno type="society">IMJ-0324-2015.R2</idno><idno type="toTypesetVersion">file:IMJ.IMJ12896.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.2015.45.issue-12</idno><idno type="product">IMJ</idno><imprint><biblScope unit="vol">45</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="1266">1266</biblScope><biblScope unit="page" to="1273">1273</biblScope><biblScope unit="page-count">9</biblScope><date type="published" when="2015-12"></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 style="main"><head>Abstract</head><head>Background</head><p>While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (‘triple therapy’) has been shown in clinical trials, few studies have examined its longevity in a real‐life setting.</p><head>Aim</head><p>Our aim was to assess the tolerability, longevity and efficacy of a triple disease‐modifying anti‐rheumatic drug (DMARD) regimen initiated in new‐onset rheumatoid arthritis (RA) patients.</p><head>Methods</head><p>Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response‐driven step‐up algorithm, which included progression to leflunomide (LEF) or a biologic agent.</p><head>Results</head><p>Of 181 new‐onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three‐DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three‐drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA).</p><head>Conclusions</head><p>Triple therapy in new‐onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.</p></abstract><textClass><keywords><term xml:id="imj12896-kwd-0001">rheumatoid arthritis</term><term xml:id="imj12896-kwd-0002">anti‐rheumatic agents</term><term xml:id="imj12896-kwd-0003">medication persistence</term></keywords><keywords rend="articleCategory"><term>Original Article</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-BL4FV68G-Q/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" xml:id="imj12896"><header><publicationMeta level="product"><doi>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></idGroup><titleGroup><title type="main" sort="INTERNAL MEDICINE JOURNAL">Internal Medicine Journal</title><title type="short">Internal Medicine Journal</title></titleGroup></publicationMeta><publicationMeta level="part" position="12112"><doi>10.1111/imj.2015.45.issue-12</doi><copyright ownership="thirdParty">Internal Medicine Journal © 2015 Royal Australasian College of Physicians</copyright><numberingGroup><numbering type="journalVolume" number="45">45</numbering><numbering type="journalIssue">12</numbering></numberingGroup><coverDate startDate="2015-12">December 2015</coverDate></publicationMeta><publicationMeta level="unit" position="100" type="article" status="forIssue"><doi>10.1111/imj.12896</doi><idGroup><id type="unit" value="IMJ12896"></id><id type="society" value="IMJ-0324-2015.R2"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Original Article</title><title type="tocHeading1">Original Articles</title></titleGroup><copyright ownership="thirdParty">© 2015 Royal Australasian College of Physicians</copyright><eventGroup><event type="manuscriptReceived" date="2015-04-28"></event><event type="manuscriptRevised" date="2015-08-26"></event><event type="manuscriptAccepted" date="2015-08-30"></event><event type="xmlCreated" agent="SPi Global" date="2015-09-16"></event><event type="publishedOnlineAccepted" date="2015-09-08"></event><event type="publishedOnlineFinalForm" date="2015-12-09"></event><event type="firstOnline" date="2015-12-09"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.7.2 mode:FullText" date="2015-12-09"></event></eventGroup><numberingGroup><numbering type="pageFirst">1266</numbering><numbering type="pageLast">1273</numbering></numberingGroup><correspondenceTo><lineatedText><line>Correspondence</line><line>Ranjeny Thomas, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Qld 4102, Australia.</line><line>Email: <email>ranjeny.thomas@uq.edu.au</email></line></lineatedText></correspondenceTo><selfCitationGroup><citation type="self" xml:id="imj12896-cit-0000"><author><familyName>Cummins</familyName>, <givenNames>L.</givenNames></author>, <author><familyName>Katikireddi</familyName>, <givenNames>V. S.</givenNames></author>, <author><familyName>Shankaranarayana</familyName>, <givenNames>S.</givenNames></author>, <author><familyName>Su</familyName>, <givenNames>K. Y. C.</givenNames></author>, <author><familyName>Duggan</familyName>, <givenNames>E.</givenNames></author>, <author><familyName>Videm</familyName>, <givenNames>V.</givenNames></author>, <author><familyName>Pahau</familyName>, <givenNames>H.</givenNames></author>, and <author><familyName>Thomas</familyName>, <givenNames>R.</givenNames></author> (<pubYear year="2015">2015</pubYear>) <articleTitle>Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis</articleTitle>. <journalTitle>Internal Medicine Journal</journalTitle>, <vol>45</vol>: <pageFirst>1266</pageFirst>–<pageLast>1273</pageLast>. doi: <accessionId ref="info:doi/10.1111/imj.12896">10.1111/imj.12896</accessionId>.</citation></selfCitationGroup><linkGroup><link type="toTypesetVersion" href="file:IMJ.IMJ12896.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis</title><title type="short">Triple DMARD therapy in new‐onset RA</title><title type="shortAuthors">Cummins <i>et al.</i></title></titleGroup><creators><creator creatorRole="author" xml:id="imj12896-cr-0001" affiliationRef="#imj12896-aff-0001 #imj12896-aff-0002"><personName><givenNames>L.</givenNames><familyName>Cummins</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0002" affiliationRef="#imj12896-aff-0001"><personName><givenNames>V. S.</givenNames><familyName>Katikireddi</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0003" affiliationRef="#imj12896-aff-0001"><personName><givenNames>S.</givenNames><familyName>Shankaranarayana</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0004" affiliationRef="#imj12896-aff-0001"><personName><givenNames>K. Y. C.</givenNames><familyName>Su</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0005" affiliationRef="#imj12896-aff-0001"><personName><givenNames>E.</givenNames><familyName>Duggan</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0006" affiliationRef="#imj12896-aff-0001 #imj12896-aff-0003 #imj12896-aff-0004"><personName><givenNames>V.</givenNames><familyName>Videm</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0007" affiliationRef="#imj12896-aff-0001"><personName><givenNames>H.</givenNames><familyName>Pahau</familyName></personName></creator><creator creatorRole="author" xml:id="imj12896-cr-0008" affiliationRef="#imj12896-aff-0001 #imj12896-aff-0002" corresponding="yes"><personName><givenNames>R.</givenNames><familyName>Thomas</familyName></personName></creator></creators><affiliationGroup><affiliation countryCode="AU" type="organization" xml:id="imj12896-aff-0001"><orgDiv>University of Queensland Diamantina Institute</orgDiv><orgName>Translational Research Institute</orgName><address><city>Brisbane</city><countryPart>Queensland</countryPart><country>Australia</country></address></affiliation><affiliation countryCode="AU" type="organization" xml:id="imj12896-aff-0002"><orgName>Princess Alexandra Hospital</orgName><address><city>Brisbane</city><countryPart>Queensland</countryPart><country>Australia</country></address></affiliation><affiliation countryCode="NO" type="organization" xml:id="imj12896-aff-0003"><orgDiv>Department of Laboratory Medicine, Children's and Women's Health</orgDiv><orgName>Norwegian University of Science and Technology</orgName><address><city>Trondheim</city><country>Norway</country></address></affiliation><affiliation countryCode="NO" type="organization" xml:id="imj12896-aff-0004"><orgDiv>Department of Immunology and Transfusion Medicine</orgDiv><orgName>St Olav University Hospital</orgName><address><city>Trondheim</city><country>Norway</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="imj12896-kwd-0001">rheumatoid arthritis</keyword><keyword xml:id="imj12896-kwd-0002">anti‐rheumatic agents</keyword><keyword xml:id="imj12896-kwd-0003">medication persistence</keyword></keywordGroup><abstractGroup><abstract type="main"><title type="main">Abstract</title><section xml:id="imj12896-sec-0001" numbered="no"><title type="main">Background</title><p>While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (‘triple therapy’) has been shown in clinical trials, few studies have examined its longevity in a real‐life setting.</p></section><section xml:id="imj12896-sec-0101" numbered="no"><title type="main">Aim</title><p>Our aim was to assess the tolerability, longevity and efficacy of a triple disease‐modifying anti‐rheumatic drug (DMARD) regimen initiated in new‐onset rheumatoid arthritis (RA) patients.</p></section><section xml:id="imj12896-sec-0002" numbered="no"><title type="main">Methods</title><p>Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response‐driven step‐up algorithm, which included progression to leflunomide (LEF) or a biologic agent.</p></section><section xml:id="imj12896-sec-0003" numbered="no"><title type="main">Results</title><p>Of 181 new‐onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three‐DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three‐drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA).</p></section><section xml:id="imj12896-sec-0004" numbered="no"><title type="main">Conclusions</title><p>Triple therapy in new‐onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.</p></section></abstract></abstractGroup></contentMeta><noteGroup xml:id="imj12896-ntgp-0001"><note xml:id="imj12896-note-0001" numbered="no">Funding: None</note><note xml:id="imj12896-note-0002" numbered="no">Conflict of interest: None.</note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Triple DMARD therapy in new‐onset RA</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis</title></titleInfo><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Cummins</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</affiliation><affiliation>Princess Alexandra Hospital, Queensland, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V. S.</namePart><namePart type="family">Katikireddi</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S.</namePart><namePart type="family">Shankaranarayana</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">K. Y. C.</namePart><namePart type="family">Su</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E.</namePart><namePart type="family">Duggan</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V.</namePart><namePart type="family">Videm</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</affiliation><affiliation>Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway</affiliation><affiliation>Department of Immunology and Transfusion Medicine, St Olav University Hospital, Trondheim, Norway</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H.</namePart><namePart type="family">Pahau</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Queensland, Brisbane, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Thomas</namePart><affiliation>University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia</affiliation><affiliation>Princess Alexandra Hospital, Queensland, Brisbane, Australia</affiliation><affiliation>CorrespondenceRanjeny Thomas, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Qld 4102, Australia.Email:</affiliation><affiliation>E-mail: ranjeny.thomas@uq.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 Ltd</publisher><dateIssued encoding="w3cdtf">2015-12</dateIssued><dateCreated encoding="w3cdtf">2015-09-16</dateCreated><dateCaptured encoding="w3cdtf">2015-04-28</dateCaptured><dateValid encoding="w3cdtf">2015-08-30</dateValid><edition>Cummins, L., Katikireddi, V. S., Shankaranarayana, S., Su, K. Y. C., Duggan, E., Videm, V., Pahau, H., and Thomas, R. (2015) Safety and retention of combination triple disease‐modifying anti‐rheumatic drugs in new‐onset rheumatoid arthritis. Internal Medicine Journal, 45: 1266–1273. doi: 10.1111/imj.12896.</edition><copyrightDate encoding="w3cdtf">2015</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract>Background: While efficacy of combination treatment with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ) (‘triple therapy’) has been shown in clinical trials, few studies have examined its longevity in a real‐life setting. Aim: Our aim was to assess the tolerability, longevity and efficacy of a triple disease‐modifying anti‐rheumatic drug (DMARD) regimen initiated in new‐onset rheumatoid arthritis (RA) patients. Methods: Patients who met 1987 American College of Rheumatology criteria for RA with disease duration less than 2 years were offered triple therapy upon diagnosis. Treatment was intensified according to a response‐driven step‐up algorithm, which included progression to leflunomide (LEF) or a biologic agent. Results: Of 181 new‐onset RA patients, 119 commenced triple therapy. Median duration of triple therapy was 39 weeks, and 23.5% remained on it at last follow up, with median follow up 104 weeks. Continuous therapy with any three‐DMARD combination (including LEF) occurred in 32% at last follow up, with median duration of 70 weeks. Cessation of at least one of MTX, SSZ or HCQ occurred because of an adverse event in 38%, remission in 7% and incomplete response in 28% of patients. SSZ accounted for 49% of initial drug withdrawals for an adverse event. Continuation of three‐drug therapy did not significantly influence the proportion of patients achieving remission or low disease activity (LDA). Conclusions: Triple therapy in new‐onset RA was reasonably well tolerated, persisting for median 39 weeks. SSZ intolerance commonly reduces longevity of triple therapy. Treating to the target of remission or LDA is more important than the number of DMARD continued.</abstract><subject><genre>keywords</genre><topic>rheumatoid arthritis</topic><topic>anti‐rheumatic agents</topic><topic>medication persistence</topic></subject><relatedItem type="host"><titleInfo><title>Internal Medicine Journal</title></titleInfo><titleInfo type="abbreviated"><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><subject><genre>article-category</genre><topic>Original Article</topic><topic>Original Articles</topic></subject><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>2015</date><detail type="volume"><caption>vol.</caption><number>45</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>1266</start><end>1273</end><total>9</total></extent></part></relatedItem><relatedItem type="references" displayLabel="imj12896-cit-0001"><titleInfo><title>EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease‐modifying antirheumatic drugs: 2013 update</title></titleInfo><name type="personal"><namePart type="given">JS</namePart><namePart type="family">Smolen</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Landewe</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">FC</namePart><namePart type="family">Breedveld</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Buch</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G</namePart><namePart type="family">Burmester</namePart><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Dougados</namePart><role><roleTerm type="text">author</roleTerm></role></name><genre>journal-article</genre><note type="citation/reference">Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M et al. 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