Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts
Identifieur interne : 000596 ( Ncbi/Merge ); précédent : 000595; suivant : 000597Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts
Auteurs : Patrick Kiely [Royaume-Uni] ; A D Busby [Royaume-Uni] ; E. Nikiphorou [Royaume-Uni] ; K. Sullivan [Royaume-Uni] ; D A Walsh [Royaume-Uni] ; P. Creamer [Royaume-Uni] ; J. Dixey [Royaume-Uni] ; A. Young [Royaume-Uni]Source :
- BMJ Open [ 2044-6055 ] ; 2019.
Abstract
To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.
Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).
Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.
Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3–6 months, at 12 months and annually thereafter.
Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.
Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.
MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.
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DOI: 10.1136/bmjopen-2018-028466
PubMed: 31061059
PubMed Central: 6501950
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Results from a multivariate analysis in the ERAS and ERAN inception cohorts</title><author><name sortKey="Kiely, Patrick" sort="Kiely, Patrick" uniqKey="Kiely P" first="Patrick" last="Kiely">Patrick Kiely</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Department of Rheumatology</institution>,<institution>St Georges University Hospitals NHS Foundation Trust</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution content-type="department">Institute of Medical and Biomedical Education</institution>,<institution>St George’s, University of London</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Busby, A D" sort="Busby, A D" uniqKey="Busby A" first="A D" last="Busby">A D Busby</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nikiphorou, E" sort="Nikiphorou, E" uniqKey="Nikiphorou E" first="E" last="Nikiphorou">E. Nikiphorou</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="department">Department of Academic Rheumatology</institution>,<institution>King’s College</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sullivan, K" sort="Sullivan, K" uniqKey="Sullivan K" first="K" last="Sullivan">K. Sullivan</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, D A" sort="Walsh, D A" uniqKey="Walsh D" first="D A" last="Walsh">D A Walsh</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="department">Department of Academic Rheumatology</institution>,<institution>University of Nottingham</institution>,<addr-line content-type="city">Nottingham</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Creamer, P" sort="Creamer, P" uniqKey="Creamer P" first="P" last="Creamer">P. Creamer</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution content-type="department">Department of Rheumatology</institution>,<institution>North Bristol NHS Trust</institution>,<addr-line content-type="city">Bristol</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dixey, J" sort="Dixey, J" uniqKey="Dixey J" first="J" last="Dixey">J. Dixey</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution content-type="department">Department of Rheumatology</institution>,<institution>The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust</institution>,<addr-line content-type="city">Shrewsbury</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Young, A" sort="Young, A" uniqKey="Young A" first="A" last="Young">A. Young</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31061059</idno><idno type="pmc">6501950</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501950</idno><idno type="RBID">PMC:6501950</idno><idno type="doi">10.1136/bmjopen-2018-028466</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000416</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000416</idno><idno type="wicri:Area/Pmc/Curation">000416</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000416</idno><idno type="wicri:Area/Pmc/Checkpoint">000655</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000655</idno><idno type="wicri:Area/Ncbi/Merge">000596</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts</title><author><name sortKey="Kiely, Patrick" sort="Kiely, Patrick" uniqKey="Kiely P" first="Patrick" last="Kiely">Patrick Kiely</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Department of Rheumatology</institution>,<institution>St Georges University Hospitals NHS Foundation Trust</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution content-type="department">Institute of Medical and Biomedical Education</institution>,<institution>St George’s, University of London</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Busby, A D" sort="Busby, A D" uniqKey="Busby A" first="A D" last="Busby">A D Busby</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nikiphorou, E" sort="Nikiphorou, E" uniqKey="Nikiphorou E" first="E" last="Nikiphorou">E. Nikiphorou</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="department">Department of Academic Rheumatology</institution>,<institution>King’s College</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sullivan, K" sort="Sullivan, K" uniqKey="Sullivan K" first="K" last="Sullivan">K. Sullivan</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, D A" sort="Walsh, D A" uniqKey="Walsh D" first="D A" last="Walsh">D A Walsh</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="department">Department of Academic Rheumatology</institution>,<institution>University of Nottingham</institution>,<addr-line content-type="city">Nottingham</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Creamer, P" sort="Creamer, P" uniqKey="Creamer P" first="P" last="Creamer">P. Creamer</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution content-type="department">Department of Rheumatology</institution>,<institution>North Bristol NHS Trust</institution>,<addr-line content-type="city">Bristol</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dixey, J" sort="Dixey, J" uniqKey="Dixey J" first="J" last="Dixey">J. Dixey</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution content-type="department">Department of Rheumatology</institution>,<institution>The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust</institution>,<addr-line content-type="city">Shrewsbury</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Young, A" sort="Young, A" uniqKey="Young A" first="A" last="Young">A. Young</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">BMJ Open</title><idno type="eISSN">2044-6055</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.</p></sec><sec><title>Design</title><p>Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).</p></sec><sec><title>Setting</title><p>Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.</p></sec><sec><title>Participants</title><p>Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3–6 months, at 12 months and annually thereafter.</p></sec><sec><title>Primary and secondary outcome measures</title><p>Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.</p></sec><sec><title>Results</title><p>Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.</p></sec><sec><title>Conclusions</title><p>MTX treatment was not associated with an increased risk of RA-ILD diagnosis. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">BMJ Open</journal-id><journal-id journal-id-type="iso-abbrev">BMJ Open</journal-id><journal-id journal-id-type="hwp">bmjopen</journal-id><journal-id journal-id-type="publisher-id">bmjopen</journal-id><journal-title-group><journal-title>BMJ Open</journal-title></journal-title-group><issn pub-type="epub">2044-6055</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31061059</article-id><article-id pub-id-type="pmc">6501950</article-id><article-id pub-id-type="publisher-id">bmjopen-2018-028466</article-id><article-id pub-id-type="doi">10.1136/bmjopen-2018-028466</article-id><article-categories><subj-group subj-group-type="heading"><subject>Rheumatology</subject><subj-group><subject>Research</subject></subj-group></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject><subject>1732</subject></subj-group></article-categories><title-group><article-title>Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts</article-title></title-group><contrib-group><contrib id="author-28279514" contrib-type="author"><name><surname>Kiely</surname><given-names>Patrick</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Busby</surname><given-names>A D</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Nikiphorou</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Sullivan</surname><given-names>K</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Walsh</surname><given-names>D A</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Creamer</surname><given-names>P</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Dixey</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Young</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib></contrib-group><aff id="aff1"><label>1</label><institution content-type="department">Department of Rheumatology</institution>,<institution>St Georges University Hospitals NHS Foundation Trust</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></aff><aff id="aff2"><label>2</label><institution content-type="department">Institute of Medical and Biomedical Education</institution>,<institution>St George’s, University of London</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></aff><aff id="aff3"><label>3</label><institution content-type="department">Center for Health Services and Clinical Research and Post Graduate Medicine</institution>,<institution>University of Hertfordshire</institution>,<addr-line content-type="city">Hatfield</addr-line>,<country>UK</country></aff><aff id="aff4"><label>4</label><institution content-type="department">Department of Academic Rheumatology</institution>,<institution>King’s College</institution>,<addr-line content-type="city">London</addr-line>,<country>UK</country></aff><aff id="aff5"><label>5</label><institution content-type="department">Department of Academic Rheumatology</institution>,<institution>University of Nottingham</institution>,<addr-line content-type="city">Nottingham</addr-line>,<country>UK</country></aff><aff id="aff6"><label>6</label><institution content-type="department">Department of Rheumatology</institution>,<institution>North Bristol NHS Trust</institution>,<addr-line content-type="city">Bristol</addr-line>,<country>UK</country></aff><aff id="aff7"><label>7</label><institution content-type="department">Department of Rheumatology</institution>,<institution>The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust</institution>,<addr-line content-type="city">Shrewsbury</addr-line>,<country>UK</country></aff><author-notes><corresp><label>Correspondence to</label> Dr Patrick Kiely; <email>patrick.kiely@stgeorges.nhs.uk</email></corresp></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>5</day><month>5</month><year>2019</year></pub-date><volume>9</volume><issue>5</issue><elocation-id>e028466</elocation-id><history><date date-type="received"><day>09</day><month>12</month><year>2018</year></date><date date-type="rev-recd"><day>25</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>29</day><month>3</month><year>2019</year></date></history><permissions><copyright-statement>© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="bmjopen-2018-028466.pdf"></self-uri><self-uri content-type="reviewers-comments-pdf" xlink:href="bmjopen-2018-028466.reviewer_comments.pdf"></self-uri><self-uri content-type="draft-revisions-pdf" xlink:href="bmjopen-2018-028466.draft_revisions.pdf"></self-uri><abstract><sec><title>Objectives</title><p>To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.</p></sec><sec><title>Design</title><p>Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).</p></sec><sec><title>Setting</title><p>Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.</p></sec><sec><title>Participants</title><p>Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3–6 months, at 12 months and annually thereafter.</p></sec><sec><title>Primary and secondary outcome measures</title><p>Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.</p></sec><sec><title>Results</title><p>Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.</p></sec><sec><title>Conclusions</title><p>MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.</p></sec></abstract><kwd-group><kwd>rheumatoid arthritis</kwd><kwd>interstitial lung disease</kwd><kwd>methotrexate</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>special-feature</meta-name><meta-value>unlocked</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Kiely, Patrick" sort="Kiely, Patrick" uniqKey="Kiely P" first="Patrick" last="Kiely">Patrick Kiely</name></noRegion><name sortKey="Busby, A D" sort="Busby, A D" uniqKey="Busby A" first="A D" last="Busby">A D Busby</name><name sortKey="Creamer, P" sort="Creamer, P" uniqKey="Creamer P" first="P" last="Creamer">P. Creamer</name><name sortKey="Dixey, J" sort="Dixey, J" uniqKey="Dixey J" first="J" last="Dixey">J. Dixey</name><name sortKey="Kiely, Patrick" sort="Kiely, Patrick" uniqKey="Kiely P" first="Patrick" last="Kiely">Patrick Kiely</name><name sortKey="Nikiphorou, E" sort="Nikiphorou, E" uniqKey="Nikiphorou E" first="E" last="Nikiphorou">E. Nikiphorou</name><name sortKey="Sullivan, K" sort="Sullivan, K" uniqKey="Sullivan K" first="K" last="Sullivan">K. Sullivan</name><name sortKey="Walsh, D A" sort="Walsh, D A" uniqKey="Walsh D" first="D A" last="Walsh">D A Walsh</name><name sortKey="Young, A" sort="Young, A" uniqKey="Young A" first="A" last="Young">A. Young</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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