Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study
Identifieur interne : 000A17 ( Pmc/Curation ); précédent : 000A16; suivant : 000A18Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study
Auteurs : D. S. Courvoisier [Suisse] ; D. Alpizar-Rodriguez [Suisse] ; J. E. Gottenberg [France] ; M. V. Hernandez [Espagne] ; F. Iannone [Italie] ; E. Lie [Norvège] ; M. J. Santos [Portugal] ; K. Pavelka [République tchèque] ; C. Turesson [Suède] ; X. Mariette [France] ; D. Choquette [Canada] ; M. L. Hetland [Danemark] ; A. Finckh [Suisse]Source :
- EBioMedicine [ 2352-3964 ] ; 2016.
Abstract
Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD).
Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes.
We identified three types of treatment response trajectories: ‘gradual responders’ (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; ‘rapid responders’ (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; ‘inadequate responders’ (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (
Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.
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DOI: 10.1016/j.ebiom.2016.08.024
PubMed: 27558858
PubMed Central: 5049989
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Lie</name><affiliation wicri:level="1"><nlm:aff id="af0025">Diakonhjemmet Hospital, Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Diakonhjemmet Hospital, Oslo</wicri:regionArea></affiliation></author><author><name sortKey="Santos, M J" sort="Santos, M J" uniqKey="Santos M" first="M. J." last="Santos">M. J. Santos</name><affiliation wicri:level="1"><nlm:aff id="af0030">Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon</wicri:regionArea></affiliation></author><author><name sortKey="Pavelka, K" sort="Pavelka, K" uniqKey="Pavelka K" first="K." last="Pavelka">K. 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Turesson</name><affiliation wicri:level="1"><nlm:aff id="af0040">Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Malmö, Lund University, Malmö</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0045">Department of Rheumatology, Skåne University Hospital, Malmö, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Rheumatology, Skåne University Hospital, Malmö</wicri:regionArea></affiliation></author><author><name sortKey="Mariette, X" sort="Mariette, X" uniqKey="Mariette X" first="X." last="Mariette">X. Mariette</name><affiliation wicri:level="1"><nlm:aff id="af0050">Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Hôpitaux Universitaires Paris-Sud, Université Paris-Sud</wicri:regionArea></affiliation></author><author><name sortKey="Choquette, D" sort="Choquette, D" uniqKey="Choquette D" first="D." last="Choquette">D. Choquette</name><affiliation wicri:level="1"><nlm:aff id="af0055">Institut de Rhumatologie de Montréal, CHUM, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Institut de Rhumatologie de Montréal, CHUM</wicri:regionArea></affiliation></author><author><name sortKey="Hetland, M L" sort="Hetland, M L" uniqKey="Hetland M" first="M. L." last="Hetland">M. L. Hetland</name><affiliation wicri:level="1"><nlm:aff id="af0060">The DANBIO registry Rigshospitalet, Glostrup, University of Copenhagen, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>The DANBIO registry Rigshospitalet, Glostrup, University of Copenhagen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0065">Department of Clinical Medicine, University of Copenhagen, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Medicine, University of Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Finckh, A" sort="Finckh, A" uniqKey="Finckh A" first="A." last="Finckh">A. Finckh</name><affiliation wicri:level="1"><nlm:aff id="af0005">University Hospitals Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>University Hospitals Geneva</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27558858</idno><idno type="pmc">5049989</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049989</idno><idno type="RBID">PMC:5049989</idno><idno type="doi">10.1016/j.ebiom.2016.08.024</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000A17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A17</idno><idno type="wicri:Area/Pmc/Curation">000A17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A17</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study</title><author><name sortKey="Courvoisier, D S" sort="Courvoisier, D S" uniqKey="Courvoisier D" first="D. S." last="Courvoisier">D. S. Courvoisier</name><affiliation wicri:level="1"><nlm:aff id="af0005">University Hospitals Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>University Hospitals Geneva</wicri:regionArea></affiliation></author><author><name sortKey="Alpizar Rodriguez, D" sort="Alpizar Rodriguez, D" uniqKey="Alpizar Rodriguez D" first="D." last="Alpizar-Rodriguez">D. Alpizar-Rodriguez</name><affiliation wicri:level="1"><nlm:aff id="af0005">University Hospitals Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>University Hospitals Geneva</wicri:regionArea></affiliation></author><author><name sortKey="Gottenberg, J E" sort="Gottenberg, J E" uniqKey="Gottenberg J" first="J. E." last="Gottenberg">J. E. Gottenberg</name><affiliation wicri:level="1"><nlm:aff id="af0010">Strasbourg University Hospital, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Strasbourg University Hospital</wicri:regionArea></affiliation></author><author><name sortKey="Hernandez, M V" sort="Hernandez, M V" uniqKey="Hernandez M" first="M. V." last="Hernandez">M. V. Hernandez</name><affiliation wicri:level="1"><nlm:aff id="af0015">Hospital Clinic of Barcelona, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Hospital Clinic of Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Iannone, F" sort="Iannone, F" uniqKey="Iannone F" first="F." last="Iannone">F. Iannone</name><affiliation wicri:level="1"><nlm:aff id="af0020">Rheumatology Unit, University Hospital, Bari, Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Rheumatology Unit, University Hospital, Bari</wicri:regionArea></affiliation></author><author><name sortKey="Lie, E" sort="Lie, E" uniqKey="Lie E" first="E." last="Lie">E. Lie</name><affiliation wicri:level="1"><nlm:aff id="af0025">Diakonhjemmet Hospital, Oslo, Norway</nlm:aff><country xml:lang="fr">Norvège</country><wicri:regionArea>Diakonhjemmet Hospital, Oslo</wicri:regionArea></affiliation></author><author><name sortKey="Santos, M J" sort="Santos, M J" uniqKey="Santos M" first="M. J." last="Santos">M. J. Santos</name><affiliation wicri:level="1"><nlm:aff id="af0030">Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal</nlm:aff><country xml:lang="fr">Portugal</country><wicri:regionArea>Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon</wicri:regionArea></affiliation></author><author><name sortKey="Pavelka, K" sort="Pavelka, K" uniqKey="Pavelka K" first="K." last="Pavelka">K. Pavelka</name><affiliation wicri:level="1"><nlm:aff id="af0035">Institute of Rheumatology, Prague, Czech Republic</nlm:aff><country xml:lang="fr">République tchèque</country><wicri:regionArea>Institute of Rheumatology, Prague</wicri:regionArea></affiliation></author><author><name sortKey="Turesson, C" sort="Turesson, C" uniqKey="Turesson C" first="C." last="Turesson">C. Turesson</name><affiliation wicri:level="1"><nlm:aff id="af0040">Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Clinical Sciences, Malmö, Lund University, Malmö</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0045">Department of Rheumatology, Skåne University Hospital, Malmö, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Rheumatology, Skåne University Hospital, Malmö</wicri:regionArea></affiliation></author><author><name sortKey="Mariette, X" sort="Mariette, X" uniqKey="Mariette X" first="X." last="Mariette">X. Mariette</name><affiliation wicri:level="1"><nlm:aff id="af0050">Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Hôpitaux Universitaires Paris-Sud, Université Paris-Sud</wicri:regionArea></affiliation></author><author><name sortKey="Choquette, D" sort="Choquette, D" uniqKey="Choquette D" first="D." last="Choquette">D. Choquette</name><affiliation wicri:level="1"><nlm:aff id="af0055">Institut de Rhumatologie de Montréal, CHUM, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Institut de Rhumatologie de Montréal, CHUM</wicri:regionArea></affiliation></author><author><name sortKey="Hetland, M L" sort="Hetland, M L" uniqKey="Hetland M" first="M. L." last="Hetland">M. L. Hetland</name><affiliation wicri:level="1"><nlm:aff id="af0060">The DANBIO registry Rigshospitalet, Glostrup, University of Copenhagen, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>The DANBIO registry Rigshospitalet, Glostrup, University of Copenhagen</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0065">Department of Clinical Medicine, University of Copenhagen, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Medicine, University of Copenhagen</wicri:regionArea></affiliation></author><author><name sortKey="Finckh, A" sort="Finckh, A" uniqKey="Finckh A" first="A." last="Finckh">A. Finckh</name><affiliation wicri:level="1"><nlm:aff id="af0005">University Hospitals Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>University Hospitals Geneva</wicri:regionArea></affiliation></author></analytic><series><title level="j">EBioMedicine</title><idno type="eISSN">2352-3964</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD).</p></sec><sec><title>Methods</title><p>Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes.</p></sec><sec><title>Findings</title><p>We identified three types of treatment response trajectories: ‘gradual responders’ (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; ‘rapid responders’ (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; ‘inadequate responders’ (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (<italic>p</italic> <italic>=</italic> <italic>0.03</italic>), and EULAR good or moderate responses at 1 year was much higher among ‘rapid responders’ (<italic>p</italic> <italic><</italic> <italic>0.001</italic>).</p></sec><sec><title>Interpretation</title><p>Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Aga, A B" uniqKey="Aga A">A.B. Aga</name></author><author><name sortKey="Lie, E" uniqKey="Lie E">E. Lie</name></author><author><name sortKey="Uhlig, T" uniqKey="Uhlig T">T. Uhlig</name></author><author><name sortKey="Olsen, I C" uniqKey="Olsen I">I.C. Olsen</name></author><author><name sortKey="Wierod, A" uniqKey="Wierod A">A. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">EBioMedicine</journal-id><journal-id journal-id-type="iso-abbrev">EBioMedicine</journal-id><journal-title-group><journal-title>EBioMedicine</journal-title></journal-title-group><issn pub-type="epub">2352-3964</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27558858</article-id><article-id pub-id-type="pmc">5049989</article-id><article-id pub-id-type="publisher-id">S2352-3964(16)30373-5</article-id><article-id pub-id-type="doi">10.1016/j.ebiom.2016.08.024</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Courvoisier</surname><given-names>D.S.</given-names></name><email>Delphine.Courvoisier@hcuge.ch</email><xref rid="af0005" ref-type="aff">a</xref><xref rid="cr0005" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author"><name><surname>Alpizar-Rodriguez</surname><given-names>D.</given-names></name><xref rid="af0005" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Gottenberg</surname><given-names>J.E.</given-names></name><xref rid="af0010" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Hernandez</surname><given-names>M.V.</given-names></name><xref rid="af0015" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>Iannone</surname><given-names>F.</given-names></name><xref rid="af0020" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Lie</surname><given-names>E.</given-names></name><xref rid="af0025" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Santos</surname><given-names>M.J.</given-names></name><xref rid="af0030" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Pavelka</surname><given-names>K.</given-names></name><xref rid="af0035" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Turesson</surname><given-names>C.</given-names></name><xref rid="af0040" ref-type="aff">h</xref><xref rid="af0045" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Mariette</surname><given-names>X.</given-names></name><xref rid="af0050" ref-type="aff">j</xref></contrib><contrib contrib-type="author"><name><surname>Choquette</surname><given-names>D.</given-names></name><xref rid="af0055" ref-type="aff">k</xref></contrib><contrib contrib-type="author"><name><surname>Hetland</surname><given-names>M.L.</given-names></name><xref rid="af0060" ref-type="aff">l</xref><xref rid="af0065" ref-type="aff">m</xref></contrib><contrib contrib-type="author"><name><surname>Finckh</surname><given-names>A.</given-names></name><xref rid="af0005" ref-type="aff">a</xref></contrib></contrib-group><aff id="af0005"><label>a</label>University Hospitals Geneva, Switzerland</aff><aff id="af0010"><label>b</label>Strasbourg University Hospital, France</aff><aff id="af0015"><label>c</label>Hospital Clinic of Barcelona, Spain</aff><aff id="af0020"><label>d</label>Rheumatology Unit, University Hospital, Bari, Italy</aff><aff id="af0025"><label>e</label>Diakonhjemmet Hospital, Oslo, Norway</aff><aff id="af0030"><label>f</label>Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal</aff><aff id="af0035"><label>g</label>Institute of Rheumatology, Prague, Czech Republic</aff><aff id="af0040"><label>h</label>Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden</aff><aff id="af0045"><label>i</label>Department of Rheumatology, Skåne University Hospital, Malmö, Sweden</aff><aff id="af0050"><label>j</label>Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, France</aff><aff id="af0055"><label>k</label>Institut de Rhumatologie de Montréal, CHUM, Canada</aff><aff id="af0060"><label>l</label>The DANBIO registry Rigshospitalet, Glostrup, University of Copenhagen, Denmark</aff><aff id="af0065"><label>m</label>Department of Clinical Medicine, University of Copenhagen, Denmark</aff><author-notes><corresp id="cr0005"><label>⁎</label>Corresponding author at: Division of Rheumatology, University Hospital of Geneva, 26, Ave Beau-Sejour, CH 1211 Geneva, Switzerland.Division of RheumatologyUniversity Hospital of Geneva26, Ave Beau-SejourGenevaCH 1211Switzerland <email>Delphine.Courvoisier@hcuge.ch</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>18</day><month>8</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><month>9</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>18</day><month>8</month><year>2016</year></pub-date><volume>11</volume><fpage>302</fpage><lpage>306</lpage><history><date date-type="received"><day>22</day><month>6</month><year>2016</year></date><date date-type="rev-recd"><day>15</day><month>8</month><year>2016</year></date><date date-type="accepted"><day>16</day><month>8</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 Forschungsgesellschaft für Arbeitsphysiologie und Arbeitschutz e.V.</copyright-statement><copyright-year>2016</copyright-year><license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p></license></permissions><abstract id="ab0005"><sec><title>Background</title><p>Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD).</p></sec><sec><title>Methods</title><p>Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes.</p></sec><sec><title>Findings</title><p>We identified three types of treatment response trajectories: ‘gradual responders’ (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; ‘rapid responders’ (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; ‘inadequate responders’ (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (<italic>p</italic> <italic>=</italic> <italic>0.03</italic>), and EULAR good or moderate responses at 1 year was much higher among ‘rapid responders’ (<italic>p</italic> <italic><</italic> <italic>0.001</italic>).</p></sec><sec><title>Interpretation</title><p>Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.</p></sec></abstract><abstract abstract-type="author-highlights" id="ab0010"><title>Highlights</title><p><list list-type="simple"><list-item id="u0005"><label>•</label><p>This study examined disease activity trajectories in a multinational cohort of 3898 rheumatoid arthritis patients.</p></list-item><list-item id="u0010"><label>•</label><p>Growth mixture models identified three groups: gradual, rapid, and inadequate responders (GR: 91·7%, RR: 5·6%, IR: 2·6%).</p></list-item><list-item id="u0015"><label>•</label><p>At baseline, groups were similar in demographic and clinical characteristics, and moderately different in function and disease activity.</p></list-item><list-item id="u0020"><label>•</label><p>The groups had large difference in drug retention and in good or moderate response rate.</p><p>Using nine national registries, this study of 3898 established RA patients initiating a new bDMARD identified distinct types of responders: gradual, rapid and inadequate responders. Neither socio-demographic nor clinical characteristics at baseline allowed the prediction of the type of response trajectory after treatment initiation, but effectiveness outcomes strongly differed, suggesting that these empirically derived subgroups have clinical relevance.</p><p>As a major aim of precision medicine is to make anti-rheumatic therapy more personalized, the detection of responder types following initiation of a specific bDMARD underscores the need to find reliable predictors of trajectories to identify patients needing a distinct treatment strategy.</p></list-item></list></p></abstract><kwd-group id="ks0005"><title>Keywords</title><kwd>Abatacept</kwd><kwd>Rheumatoid arthritis</kwd><kwd>Disease activity</kwd><kwd>DAS28</kwd><kwd>Longitudinal data</kwd><kwd>Drug retention</kwd><kwd>Response rate</kwd></kwd-group></article-meta></front><floats-group><fig id="f0005"><label>Fig. 1</label><caption><p>Class-specific DAS28 trajectories based on observed means. Time horizon was cut at 2 years to focus on the period with most available data.</p></caption><alt-text id="al0005">Fig. 1</alt-text><graphic xlink:href="gr1"></graphic></fig><fig id="f0010"><label>Fig. 2</label><caption><p>Boxplots of DAS28 values at baseline for the three types of trajectories.</p></caption><alt-text id="al0010">Fig. 2</alt-text><graphic xlink:href="gr2"></graphic></fig><table-wrap id="t0005" position="float"><label>Table 1</label><caption><p>Characteristics and outcomes of the patients in each of the three trajectories' type.</p></caption><alt-text id="al0015">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th></th><th>‘Gradual Responders’</th><th>‘Rapid responders’</th><th>‘inadequate responders’</th><th><italic>p</italic></th></tr></thead><tbody><tr><td>Number of patients, n (%)</td><td>3576 (91.7%)</td><td>219 (5.6%)</td><td>103 (2.6%)</td><td></td></tr><tr><td>Time follow-up, years, mean (SD)</td><td>2.0 (1.7)</td><td>2.2 (2.2)</td><td>2.1 (1.6)</td><td></td></tr><tr><td>Number of assessments, mean (SD)</td><td>3.9 (3.9)</td><td>5.0 (4.9)</td><td>4.5 (2.4)</td><td></td></tr><tr><td>Age, years, mean (SD)</td><td>57.6 (13.0)</td><td>56.6 (12.7)</td><td>59.2 (12.6)</td><td>0.22</td></tr><tr><td>BMI, mean (SD)</td><td>25.8 (5.2)</td><td>26.1 (5.7)</td><td>28.1 (5.1)</td><td>0.10</td></tr><tr><td>Female, n (%)</td><td>2866 (80.1%)</td><td>187 (85.4%)</td><td>85 (82.5%)</td><td>0.14</td></tr><tr><td>Ever smoker, n (%)</td><td>582 (17.6%)</td><td>36 (17.2%)</td><td>14 (14.3%)</td><td>0.70</td></tr><tr><td>RF, n (%)</td><td>1521 (68.2%)</td><td>87 (64.4%)</td><td>47 (74.6%)</td><td>0.36</td></tr><tr><td>ACPA, n (%)</td><td>1165 (57.8%)</td><td>67 (51.5%)</td><td>41 (68.3%)</td><td>0.09</td></tr><tr><td>Disease duration, years, mean (SD)</td><td>12.5 (9.9)</td><td>11.9 (9.1)</td><td>12.7 (9.0)</td><td>0.63</td></tr><tr><td>HAQ, mean (SD)</td><td>1.1 (0.7)</td><td>1.7 (0.6)</td><td>1.3 (0.8)</td><td>< 0.001</td></tr><tr><td>Tender joints at baseline, mean (SD)</td><td>4.6 (5.3)</td><td>10.1 (7.1)</td><td>5.2 (6.6)</td><td>< 0.001</td></tr><tr><td>Swollen joints at baseline, mean (SD)</td><td>3.1 (3.7)</td><td>7.3 (6.2)</td><td>4.4 (4.4)</td><td>< 0.001</td></tr><tr><td>ESR at baseline, mean (SD)</td><td>23.3 (18.6)</td><td>36.2 (28.1)</td><td>32.1 (22.0)</td><td>< 0.001</td></tr><tr><td>CRP at baseline, mean (SD)</td><td>9.5 (16.1)</td><td>20.3 (32.7)</td><td>11.7 (16.0)</td><td>< 0.001</td></tr><tr><td>Patient global assessment, mean (SD)</td><td>47.5 (25.4)</td><td>61.5 (21.2)</td><td>45.0 (28.5)</td><td>< 0.001</td></tr><tr><td>DAS 28 at baseline, mean (SD)</td><td>4.1 (1.0)</td><td>5.8 (1.1)</td><td>5.1 (1.1)</td><td>< 0.001</td></tr><tr><td>N. past biologics, median [<italic>IQR</italic>]</td><td>1 [1; 2]</td><td>2 [1; 3]</td><td>2 [1; 3.5]</td><td>< 0.001</td></tr><tr><td>N past cDMARD, median [<italic>IQR</italic>]</td><td>2 [1; 4]</td><td>2.5 [1; 4]</td><td>3 [1; 4]</td><td>0.03</td></tr><tr><td>Glucocorticoids at baseline, n (%)</td><td>1773 (66.4%)</td><td>120 (67.4%)</td><td>66 (77.6%)</td><td>0.09</td></tr><tr><td>Comorbidities, n (%)</td><td></td><td></td><td></td><td></td></tr><tr><td> Metabolic disease</td><td>47 (1.3%)</td><td>4 (1.8%)</td><td>0 (0.0%)</td><td>0.49</td></tr><tr><td> CV disease</td><td>80 (2.2%)</td><td>6 (2.7%)</td><td>2 (1.9%)</td><td>0.86</td></tr><tr><td> Infectious disease</td><td>35 (1.0%)</td><td>1 (0.5%)</td><td>0 (0.0%)</td><td>0.69</td></tr><tr><td> Cancer</td><td>8 (0.2%)</td><td>0 (0.0%)</td><td>0 (0.0%)</td><td>1.00</td></tr><tr><td>ABA drug retention<xref rid="tf0005" ref-type="table-fn">a</xref>, years, median[95% CI]</td><td></td><td></td><td></td><td></td></tr><tr><td> Overall</td><td>2.3 [2.1; 2.5]</td><td>1.6 [1.3; 3.0]</td><td>1.5 [1.4; 2.0]</td><td>0.11</td></tr><tr><td> Until ineffectiveness</td><td>4.7 [4.3; 5.1]</td><td>5.3 [2.6; −]</td><td>2.0 [1.7; −]</td><td>0.03</td></tr><tr><td>ABA discontinuation, n (%)</td><td>1981 (55.4%)</td><td>135 (61.6%)</td><td>78 (75.7%)</td><td>< 0.001</td></tr><tr><td>Reasons for discontinuation<xref rid="tf0010" ref-type="table-fn">b</xref>, n (%)</td><td></td><td></td><td></td><td>0.17</td></tr><tr><td> For adverse events</td><td>333 (16.8%)</td><td>12 (8.9%)</td><td>9 (11.5%)</td><td></td></tr><tr><td> For remission</td><td>19 (1.0%)</td><td>1 (0.7%)</td><td>0 (0.0%)</td><td></td></tr><tr><td> For other reasons</td><td>483 (24.4%)</td><td>31 (23.0%)</td><td>20 (25.6%)</td><td></td></tr><tr><td> For ineffectiveness</td><td>1146 (57.8%)</td><td>91 (67.4%)</td><td>49 (62.8%)</td><td></td></tr><tr><td>EULAR moderate or good response</td><td></td><td></td><td></td><td></td></tr><tr><td> At 6 months, n (%)</td><td>645 (24.3)</td><td>31 (21.2)</td><td>31 (32.9)</td><td>0.11</td></tr><tr><td> At 6 months, % Lundex</td><td>21.8</td><td>16.3</td><td>32.9</td><td></td></tr><tr><td> At 1 year, n (%)</td><td>600 (30.8)</td><td>70 (66.0)</td><td>6 (8.2)</td><td>< 0.001</td></tr><tr><td> At 1 year, % Lundex</td><td>22.1</td><td>39.2</td><td>6.4</td><td></td></tr><tr><td> At 2 years, n(%)</td><td>647 (54.9)</td><td>68 (94.4)</td><td>3 (10.0)</td><td>< 0.001</td></tr><tr><td> At 2 years, % Lundex</td><td>29.8</td><td>46.1</td><td>3.9</td><td></td></tr><tr><td>Low disease activity (DAS28 < 3.2)</td><td></td><td></td><td></td><td></td></tr><tr><td> At 6 months, N (%)</td><td>1120 (33.4)</td><td>15 (7.3)</td><td>16 (16.5)</td><td>< 0.001</td></tr><tr><td> At 1 year, N (%)</td><td>1256 (36.5)</td><td>36 (17.1)</td><td>1 (1.0)</td><td>< 0.001</td></tr><tr><td> At 2 years, N (%)</td><td>1433 (41.3)</td><td>54 (25.7)</td><td>1 (1.0)</td><td>< 0.001</td></tr></tbody></table><table-wrap-foot><fn id="tf0005"><label>a</label><p id="np0005">Estimated using Kaplan-Meier estimation.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tf0010"><label>b</label><p id="np0010">Other reasons include discontinuation due to pregnancy, surgery, and missing information on the specific reason for drug discontinuation.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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