Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial
Identifieur interne : 000417 ( Main/Exploration ); précédent : 000416; suivant : 000418Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial
Auteurs : Matthijs S. Van Der Leeuw [Pays-Bas] ; Paco M. J. Welsing [Pays-Bas] ; Maria J. H. De Hair [Pays-Bas] ; Johannes W. G. Jacobs [Pays-Bas] ; Anne C. A. Marijnissen [Pays-Bas] ; Suzanne P. Linn-Rasker [Pays-Bas] ; Faouzia Fodili [Pays-Bas] ; Reinhard Bos [Pays-Bas] ; Janneke Tekstra [Pays-Bas] ; Jacob M. Van Laar [Pays-Bas]Source :
- Trials [ 1745-6215 ] ; 2020.
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, predominantly affecting joints, which is initially treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). In RA patients with insufficient response to csDMARDs, the addition of prednisone or tocilizumab, a biological DMARD (bDMARD), to the medication has been shown to be effective in reducing RA symptoms. However, which of these two treatment strategies has superior effectiveness and safety is unknown.
In this multicenter, investigator-initiated, open-label, randomized, pragmatic trial, we aim to recruit 120 RA patients meeting the 2010 ACR/EULAR classification criteria for RA, with active disease defined as a Clinical Disease Activity Index (CDAI) > 10 and at least one swollen joint of the 28 assessed. Patients must be on stable treatment with csDMARDs for ≥ 8 weeks prior to screening and must have been treated with ≥ 2 DMARDs, of which a maximum of one tumor necrosis factor inhibitor (a class of bDMARDs) is allowed. Previous use of other bDMARDs or targeted synthetic DMARDs is not allowed. Patients will be randomized in a 1:1 ratio to receive either tocilizumab (subcutaneously at 162 mg/week) or prednisone (orally at 10 mg/day) as an addition to their current csDMARD therapy. Study visits will be performed at screening; baseline; and months 1, 2, 3, 6, 9, and 12. Study medication will be tapered in case of clinical remission (CDAI ≤ 2.8 and ≤ 1 swollen joint at two consecutive 3-monthly visits) with careful monitoring of disease activity. In case of persistent high disease activity at or after month 3 (CDAI > 22 at any visit or > 10 at two consecutive visits), patients will switch to the other strategy arm. Primary outcome is a change in CDAI from baseline to 12 months. Secondary outcomes are additional clinical response and quality of life measures, drug retention rate, radiographically detectable progression of joint damage, functional ability, and cost utility. Safety outcomes include tocilizumab-associated adverse events (AEs), glucocorticoid-associated AEs, and serious AEs.
This will be the first randomized clinical trial comparing addition of oral prednisone or of tocilizumab head to head in RA patients with insufficient response to csDMARD therapy. It will yield important information for clinical rheumatology practice.
This trial was prospectively registered in the Netherlands Trial Register on October 7, 2019 (
Url:
DOI: 10.1186/s13063-020-04260-y
PubMed: 32248829
PubMed Central: 7133012
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000399
- to stream Pmc, to step Curation: 000399
- to stream Pmc, to step Checkpoint: 000289
- to stream PubMed, to step Corpus: 000080
- to stream PubMed, to step Curation: 000080
- to stream PubMed, to step Checkpoint: 000172
- to stream Ncbi, to step Merge: 002A90
- to stream Ncbi, to step Curation: 002A90
- to stream Ncbi, to step Checkpoint: 002A90
- to stream Main, to step Merge: 000417
- to stream Main, to step Curation: 000417
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial</title>
<author><name sortKey="Van Der Leeuw, Matthijs S" sort="Van Der Leeuw, Matthijs S" uniqKey="Van Der Leeuw M" first="Matthijs S." last="Van Der Leeuw">Matthijs S. Van Der Leeuw</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Welsing, Paco M J" sort="Welsing, Paco M J" uniqKey="Welsing P" first="Paco M. J." last="Welsing">Paco M. J. Welsing</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="De Hair, Maria J H" sort="De Hair, Maria J H" uniqKey="De Hair M" first="Maria J. H." last="De Hair">Maria J. H. De Hair</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jacobs, Johannes W G" sort="Jacobs, Johannes W G" uniqKey="Jacobs J" first="Johannes W. G." last="Jacobs">Johannes W. G. Jacobs</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marijnissen, Anne C A" sort="Marijnissen, Anne C A" uniqKey="Marijnissen A" first="Anne C. A." last="Marijnissen">Anne C. A. Marijnissen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Linn Rasker, Suzanne P" sort="Linn Rasker, Suzanne P" uniqKey="Linn Rasker S" first="Suzanne P." last="Linn-Rasker">Suzanne P. Linn-Rasker</name>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.414725.1</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0368 8146</institution-id>
<institution>Meander Medical Center,</institution>
</institution-wrap>
Maatweg 3, 3813 TZ Amersfoort, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Maatweg 3, 3813 TZ Amersfoort</wicri:regionArea>
<wicri:noRegion>3813 TZ Amersfoort</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fodili, Faouzia" sort="Fodili, Faouzia" uniqKey="Fodili F" first="Faouzia" last="Fodili">Faouzia Fodili</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3">Reumazorg Zuid West Nederland, Streuvelslaan 18, 4707 CH Roosendaal, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Reumazorg Zuid West Nederland, Streuvelslaan 18, 4707 CH Roosendaal</wicri:regionArea>
<wicri:noRegion>4707 CH Roosendaal</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bos, Reinhard" sort="Bos, Reinhard" uniqKey="Bos R" first="Reinhard" last="Bos">Reinhard Bos</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.414846.b</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0419 3743</institution-id>
<institution>Medical Center Leeuwarden,</institution>
</institution-wrap>
Henri Dunantweg 2, 8934 AD Leeuwarden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Henri Dunantweg 2, 8934 AD Leeuwarden</wicri:regionArea>
<wicri:noRegion>8934 AD Leeuwarden</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tekstra, Janneke" sort="Tekstra, Janneke" uniqKey="Tekstra J" first="Janneke" last="Tekstra">Janneke Tekstra</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Laar, Jacob M" sort="Van Laar, Jacob M" uniqKey="Van Laar J" first="Jacob M." last="Van Laar">Jacob M. Van Laar</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">32248829</idno>
<idno type="pmc">7133012</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133012</idno>
<idno type="RBID">PMC:7133012</idno>
<idno type="doi">10.1186/s13063-020-04260-y</idno>
<date when="2020">2020</date>
<idno type="wicri:Area/Pmc/Corpus">000399</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000399</idno>
<idno type="wicri:Area/Pmc/Curation">000399</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000399</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000289</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000289</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="RBID">pubmed:32248829</idno>
<idno type="wicri:Area/PubMed/Corpus">000080</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000080</idno>
<idno type="wicri:Area/PubMed/Curation">000080</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000080</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000172</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000172</idno>
<idno type="wicri:Area/Ncbi/Merge">002A90</idno>
<idno type="wicri:Area/Ncbi/Curation">002A90</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002A90</idno>
<idno type="wicri:Area/Main/Merge">000417</idno>
<idno type="wicri:Area/Main/Curation">000417</idno>
<idno type="wicri:Area/Main/Exploration">000417</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial</title>
<author><name sortKey="Van Der Leeuw, Matthijs S" sort="Van Der Leeuw, Matthijs S" uniqKey="Van Der Leeuw M" first="Matthijs S." last="Van Der Leeuw">Matthijs S. Van Der Leeuw</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Welsing, Paco M J" sort="Welsing, Paco M J" uniqKey="Welsing P" first="Paco M. J." last="Welsing">Paco M. J. Welsing</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="De Hair, Maria J H" sort="De Hair, Maria J H" uniqKey="De Hair M" first="Maria J. H." last="De Hair">Maria J. H. De Hair</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jacobs, Johannes W G" sort="Jacobs, Johannes W G" uniqKey="Jacobs J" first="Johannes W. G." last="Jacobs">Johannes W. G. Jacobs</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marijnissen, Anne C A" sort="Marijnissen, Anne C A" uniqKey="Marijnissen A" first="Anne C. A." last="Marijnissen">Anne C. A. Marijnissen</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Linn Rasker, Suzanne P" sort="Linn Rasker, Suzanne P" uniqKey="Linn Rasker S" first="Suzanne P." last="Linn-Rasker">Suzanne P. Linn-Rasker</name>
<affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.414725.1</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0368 8146</institution-id>
<institution>Meander Medical Center,</institution>
</institution-wrap>
Maatweg 3, 3813 TZ Amersfoort, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Maatweg 3, 3813 TZ Amersfoort</wicri:regionArea>
<wicri:noRegion>3813 TZ Amersfoort</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fodili, Faouzia" sort="Fodili, Faouzia" uniqKey="Fodili F" first="Faouzia" last="Fodili">Faouzia Fodili</name>
<affiliation wicri:level="1"><nlm:aff id="Aff3">Reumazorg Zuid West Nederland, Streuvelslaan 18, 4707 CH Roosendaal, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Reumazorg Zuid West Nederland, Streuvelslaan 18, 4707 CH Roosendaal</wicri:regionArea>
<wicri:noRegion>4707 CH Roosendaal</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bos, Reinhard" sort="Bos, Reinhard" uniqKey="Bos R" first="Reinhard" last="Bos">Reinhard Bos</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.414846.b</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0419 3743</institution-id>
<institution>Medical Center Leeuwarden,</institution>
</institution-wrap>
Henri Dunantweg 2, 8934 AD Leeuwarden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Henri Dunantweg 2, 8934 AD Leeuwarden</wicri:regionArea>
<wicri:noRegion>8934 AD Leeuwarden</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tekstra, Janneke" sort="Tekstra, Janneke" uniqKey="Tekstra J" first="Janneke" last="Tekstra">Janneke Tekstra</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Laar, Jacob M" sort="Van Laar, Jacob M" uniqKey="Van Laar J" first="Jacob M." last="Van Laar">Jacob M. Van Laar</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Heidelberglaan 100, 3584 CX Utrecht</wicri:regionArea>
<wicri:noRegion>3584 CX Utrecht</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Trials</title>
<idno type="eISSN">1745-6215</idno>
<imprint><date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p id="Par1">Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, predominantly affecting joints, which is initially treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). In RA patients with insufficient response to csDMARDs, the addition of prednisone or tocilizumab, a biological DMARD (bDMARD), to the medication has been shown to be effective in reducing RA symptoms. However, which of these two treatment strategies has superior effectiveness and safety is unknown.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">In this multicenter, investigator-initiated, open-label, randomized, pragmatic trial, we aim to recruit 120 RA patients meeting the 2010 ACR/EULAR classification criteria for RA, with active disease defined as a Clinical Disease Activity Index (CDAI) > 10 and at least one swollen joint of the 28 assessed. Patients must be on stable treatment with csDMARDs for ≥ 8 weeks prior to screening and must have been treated with ≥ 2 DMARDs, of which a maximum of one tumor necrosis factor inhibitor (a class of bDMARDs) is allowed. Previous use of other bDMARDs or targeted synthetic DMARDs is not allowed. Patients will be randomized in a 1:1 ratio to receive either tocilizumab (subcutaneously at 162 mg/week) or prednisone (orally at 10 mg/day) as an addition to their current csDMARD therapy. Study visits will be performed at screening; baseline; and months 1, 2, 3, 6, 9, and 12. Study medication will be tapered in case of clinical remission (CDAI ≤ 2.8 and ≤ 1 swollen joint at two consecutive 3-monthly visits) with careful monitoring of disease activity. In case of persistent high disease activity at or after month 3 (CDAI > 22 at any visit or > 10 at two consecutive visits), patients will switch to the other strategy arm. Primary outcome is a change in CDAI from baseline to 12 months. Secondary outcomes are additional clinical response and quality of life measures, drug retention rate, radiographically detectable progression of joint damage, functional ability, and cost utility. Safety outcomes include tocilizumab-associated adverse events (AEs), glucocorticoid-associated AEs, and serious AEs.</p>
</sec>
<sec><title>Discussion</title>
<p id="Par3">This will be the first randomized clinical trial comparing addition of oral prednisone or of tocilizumab head to head in RA patients with insufficient response to csDMARD therapy. It will yield important information for clinical rheumatology practice.</p>
</sec>
<sec><title>Trial registration</title>
<p id="Par4">This trial was prospectively registered in the Netherlands Trial Register on October 7, 2019 (<ext-link ext-link-type="uri" xlink:href="https://www.trialregister.nl/trial/8070">NL8070</ext-link>
). The Netherlands Trial Register contains all items from the World Health Organization Trial Registration Data Set.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Uhlig, T" uniqKey="Uhlig T">T Uhlig</name>
</author>
<author><name sortKey="Moe, Rh" uniqKey="Moe R">RH Moe</name>
</author>
<author><name sortKey="Kvien, Tk" uniqKey="Kvien T">TK Kvien</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Smolen, Js" uniqKey="Smolen J">JS Smolen</name>
</author>
<author><name sortKey="Landewe, R" uniqKey="Landewe R">R Landewé</name>
</author>
<author><name sortKey="Bijlsma, J" uniqKey="Bijlsma J">J Bijlsma</name>
</author>
<author><name sortKey="Burmester, G" uniqKey="Burmester G">G Burmester</name>
</author>
<author><name sortKey="Chatzidionysiou, K" uniqKey="Chatzidionysiou K">K Chatzidionysiou</name>
</author>
<author><name sortKey="Dougados, M" uniqKey="Dougados M">M Dougados</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bijlsma, Jwj" uniqKey="Bijlsma J">JWJ Bijlsma</name>
</author>
<author><name sortKey="Hoes, Jn" uniqKey="Hoes J">JN Hoes</name>
</author>
<author><name sortKey="Van Everdingen, Aa" uniqKey="Van Everdingen A">AA Van Everdingen</name>
</author>
<author><name sortKey="Verstappen, Smm" uniqKey="Verstappen S">SMM Verstappen</name>
</author>
<author><name sortKey="Jacobs, Jwg" uniqKey="Jacobs J">JWG Jacobs</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Everdingen, Aa" uniqKey="Van Everdingen A">AA van Everdingen</name>
</author>
<author><name sortKey="Jacobs, Jwg" uniqKey="Jacobs J">JWG Jacobs</name>
</author>
<author><name sortKey="Siewertsz Van Reesema, Dr" uniqKey="Siewertsz Van Reesema D">DR Siewertsz Van Reesema</name>
</author>
<author><name sortKey="Bijlsma, Jwj" uniqKey="Bijlsma J">JWJ Bijlsma</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bakker, Mf" uniqKey="Bakker M">MF Bakker</name>
</author>
<author><name sortKey="Jacobs, Jwg" uniqKey="Jacobs J">JWG Jacobs</name>
</author>
<author><name sortKey="Welsing, Pmj" uniqKey="Welsing P">PMJ Welsing</name>
</author>
<author><name sortKey="Verstappen, Smm" uniqKey="Verstappen S">SMM Verstappen</name>
</author>
<author><name sortKey="Tekstra, J" uniqKey="Tekstra J">J Tekstra</name>
</author>
<author><name sortKey="Ton, E" uniqKey="Ton E">E Ton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aletaha, D" uniqKey="Aletaha D">D Aletaha</name>
</author>
<author><name sortKey="Smolen, Js" uniqKey="Smolen J">JS Smolen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nam, Jl" uniqKey="Nam J">JL Nam</name>
</author>
<author><name sortKey="Takase Minegishi, K" uniqKey="Takase Minegishi K">K Takase-Minegishi</name>
</author>
<author><name sortKey="Ramiro, S" uniqKey="Ramiro S">S Ramiro</name>
</author>
<author><name sortKey="Chatzidionysiou, K" uniqKey="Chatzidionysiou K">K Chatzidionysiou</name>
</author>
<author><name sortKey="Smolen, Js" uniqKey="Smolen J">JS Smolen</name>
</author>
<author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D van der Heijde</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Huoponen, S" uniqKey="Huoponen S">S Huoponen</name>
</author>
<author><name sortKey="Aaltonen, Kj" uniqKey="Aaltonen K">KJ Aaltonen</name>
</author>
<author><name sortKey="Viikinkoski, J" uniqKey="Viikinkoski J">J Viikinkoski</name>
</author>
<author><name sortKey="Rutanen, J" uniqKey="Rutanen J">J Rutanen</name>
</author>
<author><name sortKey="Relas, H" uniqKey="Relas H">H Relas</name>
</author>
<author><name sortKey="Taimen, K" uniqKey="Taimen K">K Taimen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Krasselt, M" uniqKey="Krasselt M">M Krasselt</name>
</author>
<author><name sortKey="Baerwald, C" uniqKey="Baerwald C">C Baerwald</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pincus, T" uniqKey="Pincus T">T Pincus</name>
</author>
<author><name sortKey="Cutolo, M" uniqKey="Cutolo M">M Cutolo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ravindran, V" uniqKey="Ravindran V">V Ravindran</name>
</author>
<author><name sortKey="Rachapalli, S" uniqKey="Rachapalli S">S Rachapalli</name>
</author>
<author><name sortKey="Choy, Eh" uniqKey="Choy E">EH Choy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Verhoeven, Mm" uniqKey="Verhoeven M">MM Verhoeven</name>
</author>
<author><name sortKey="De Hair, Mj" uniqKey="De Hair M">MJ de Hair</name>
</author>
<author><name sortKey="Tekstra, J" uniqKey="Tekstra J">J Tekstra</name>
</author>
<author><name sortKey="Bijlsma, Jw" uniqKey="Bijlsma J">JW Bijlsma</name>
</author>
<author><name sortKey="Van Laar, Jm" uniqKey="Van Laar J">JM van Laar</name>
</author>
<author><name sortKey="Pethoe Schramm, A" uniqKey="Pethoe Schramm A">A Pethoe-Schramm</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bijlsma, Jwj" uniqKey="Bijlsma J">JWJ Bijlsma</name>
</author>
<author><name sortKey="Welsing, Pmj" uniqKey="Welsing P">PMJ Welsing</name>
</author>
<author><name sortKey="Woodworth, Tg" uniqKey="Woodworth T">TG Woodworth</name>
</author>
<author><name sortKey="Middelink, Lm" uniqKey="Middelink L">LM Middelink</name>
</author>
<author><name sortKey="Petho Schramm, A" uniqKey="Petho Schramm A">A Pethö-Schramm</name>
</author>
<author><name sortKey="Bernasconi, C" uniqKey="Bernasconi C">C Bernasconi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schoels, M" uniqKey="Schoels M">M Schoels</name>
</author>
<author><name sortKey="Alasti, F" uniqKey="Alasti F">F Alasti</name>
</author>
<author><name sortKey="Smolen, Js" uniqKey="Smolen J">JS Smolen</name>
</author>
<author><name sortKey="Aletaha, D" uniqKey="Aletaha D">D Aletaha</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Seror, R" uniqKey="Seror R">R Seror</name>
</author>
<author><name sortKey="Dougados, M" uniqKey="Dougados M">M Dougados</name>
</author>
<author><name sortKey="Gossec, L" uniqKey="Gossec L">L Gossec</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fortunet, C" uniqKey="Fortunet C">C Fortunet</name>
</author>
<author><name sortKey="Pers, Ym" uniqKey="Pers Y">YM Pers</name>
</author>
<author><name sortKey="Lambert, J" uniqKey="Lambert J">J Lambert</name>
</author>
<author><name sortKey="Godfrin Valnet, M" uniqKey="Godfrin Valnet M">M Godfrin-Valnet</name>
</author>
<author><name sortKey="Constant, E" uniqKey="Constant E">E Constant</name>
</author>
<author><name sortKey="Devilliers, H" uniqKey="Devilliers H">H Devilliers</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Onna, M" uniqKey="Van Onna M">M Van Onna</name>
</author>
<author><name sortKey="Ten Cate, Df" uniqKey="Ten Cate D">DF Ten Cate</name>
</author>
<author><name sortKey="Tsoi, Kl" uniqKey="Tsoi K">KL Tsoi</name>
</author>
<author><name sortKey="Meier, Ajl" uniqKey="Meier A">AJL Meier</name>
</author>
<author><name sortKey="Jacobs, Jwg" uniqKey="Jacobs J">JWG Jacobs</name>
</author>
<author><name sortKey="Westgeest, Aaa" uniqKey="Westgeest A">AAA Westgeest</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aletaha, D" uniqKey="Aletaha D">D Aletaha</name>
</author>
<author><name sortKey="Neogi, T" uniqKey="Neogi T">T Neogi</name>
</author>
<author><name sortKey="Silman, Aj" uniqKey="Silman A">AJ Silman</name>
</author>
<author><name sortKey="Funovits, J" uniqKey="Funovits J">J Funovits</name>
</author>
<author><name sortKey="Felson, Dt" uniqKey="Felson D">DT Felson</name>
</author>
<author><name sortKey="Bingham, Co" uniqKey="Bingham C">CO Bingham</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Herdman, M" uniqKey="Herdman M">M Herdman</name>
</author>
<author><name sortKey="Gudex, C" uniqKey="Gudex C">C Gudex</name>
</author>
<author><name sortKey="Lloyd, A" uniqKey="Lloyd A">A Lloyd</name>
</author>
<author><name sortKey="Janssen, M" uniqKey="Janssen M">M Janssen</name>
</author>
<author><name sortKey="Kind, P" uniqKey="Kind P">P Kind</name>
</author>
<author><name sortKey="Parkin, D" uniqKey="Parkin D">D Parkin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fries, Jf" uniqKey="Fries J">JF Fries</name>
</author>
<author><name sortKey="Spitz, P" uniqKey="Spitz P">P Spitz</name>
</author>
<author><name sortKey="Kraines, Rg" uniqKey="Kraines R">RG Kraines</name>
</author>
<author><name sortKey="Holman, Hr" uniqKey="Holman H">HR Holman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cella, D" uniqKey="Cella D">D Cella</name>
</author>
<author><name sortKey="Yount, S" uniqKey="Yount S">S Yount</name>
</author>
<author><name sortKey="Sorensen, M" uniqKey="Sorensen M">M Sorensen</name>
</author>
<author><name sortKey="Chartash, E" uniqKey="Chartash E">E Chartash</name>
</author>
<author><name sortKey="Sengupta, N" uniqKey="Sengupta N">N Sengupta</name>
</author>
<author><name sortKey="Grober, J" uniqKey="Grober J">J Grober</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Buysse, Dj" uniqKey="Buysse D">DJ Buysse</name>
</author>
<author><name sortKey="Reynolds, Cf" uniqKey="Reynolds C">CF Reynolds</name>
</author>
<author><name sortKey="Monk, Th" uniqKey="Monk T">TH Monk</name>
</author>
<author><name sortKey="Berman, Sr" uniqKey="Berman S">SR Berman</name>
</author>
<author><name sortKey="Kupfer, Dj" uniqKey="Kupfer D">DJ Kupfer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zigmond, As" uniqKey="Zigmond A">AS Zigmond</name>
</author>
<author><name sortKey="Snaith, Rp" uniqKey="Snaith R">RP Snaith</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Miloslavsky, Em" uniqKey="Miloslavsky E">EM Miloslavsky</name>
</author>
<author><name sortKey="Naden, Rp" uniqKey="Naden R">RP Naden</name>
</author>
<author><name sortKey="Bijlsma, Jwj" uniqKey="Bijlsma J">JWJ Bijlsma</name>
</author>
<author><name sortKey="Brogan, Pa" uniqKey="Brogan P">PA Brogan</name>
</author>
<author><name sortKey="Brown, Es" uniqKey="Brown E">ES Brown</name>
</author>
<author><name sortKey="Brunetta, P" uniqKey="Brunetta P">P Brunetta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sampson, Ha" uniqKey="Sampson H">HA Sampson</name>
</author>
<author><name sortKey="Mu Oz Furlong, A" uniqKey="Mu Oz Furlong A">A Muñoz-Furlong</name>
</author>
<author><name sortKey="Campbell, Rl" uniqKey="Campbell R">RL Campbell</name>
</author>
<author><name sortKey="Adkinson, Nf" uniqKey="Adkinson N">NF Adkinson</name>
</author>
<author><name sortKey="Bock, Sa" uniqKey="Bock S">SA Bock</name>
</author>
<author><name sortKey="Branum, A" uniqKey="Branum A">A Branum</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Brand, J" uniqKey="Brand J">J Brand</name>
</author>
<author><name sortKey="Van Buuren, S" uniqKey="Van Buuren S">S van Buuren</name>
</author>
<author><name sortKey="Le Cessie, S" uniqKey="Le Cessie S">S le Cessie</name>
</author>
<author><name sortKey="Van Den Hout, W" uniqKey="Van Den Hout W">W van den Hout</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Pays-Bas</li>
</country>
</list>
<tree><country name="Pays-Bas"><noRegion><name sortKey="Van Der Leeuw, Matthijs S" sort="Van Der Leeuw, Matthijs S" uniqKey="Van Der Leeuw M" first="Matthijs S." last="Van Der Leeuw">Matthijs S. Van Der Leeuw</name>
</noRegion>
<name sortKey="Bos, Reinhard" sort="Bos, Reinhard" uniqKey="Bos R" first="Reinhard" last="Bos">Reinhard Bos</name>
<name sortKey="De Hair, Maria J H" sort="De Hair, Maria J H" uniqKey="De Hair M" first="Maria J. H." last="De Hair">Maria J. H. De Hair</name>
<name sortKey="Fodili, Faouzia" sort="Fodili, Faouzia" uniqKey="Fodili F" first="Faouzia" last="Fodili">Faouzia Fodili</name>
<name sortKey="Jacobs, Johannes W G" sort="Jacobs, Johannes W G" uniqKey="Jacobs J" first="Johannes W. G." last="Jacobs">Johannes W. G. Jacobs</name>
<name sortKey="Linn Rasker, Suzanne P" sort="Linn Rasker, Suzanne P" uniqKey="Linn Rasker S" first="Suzanne P." last="Linn-Rasker">Suzanne P. Linn-Rasker</name>
<name sortKey="Marijnissen, Anne C A" sort="Marijnissen, Anne C A" uniqKey="Marijnissen A" first="Anne C. A." last="Marijnissen">Anne C. A. Marijnissen</name>
<name sortKey="Tekstra, Janneke" sort="Tekstra, Janneke" uniqKey="Tekstra J" first="Janneke" last="Tekstra">Janneke Tekstra</name>
<name sortKey="Van Laar, Jacob M" sort="Van Laar, Jacob M" uniqKey="Van Laar J" first="Jacob M." last="Van Laar">Jacob M. Van Laar</name>
<name sortKey="Welsing, Paco M J" sort="Welsing, Paco M J" uniqKey="Welsing P" first="Paco M. J." last="Welsing">Paco M. J. Welsing</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/TocilizumabV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000417 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000417 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= TocilizumabV1 |flux= Main |étape= Exploration |type= RBID |clé= PMC:7133012 |texte= Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:32248829" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \ | NlmPubMed2Wicri -a TocilizumabV1
This area was generated with Dilib version V0.6.34. |