Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials
Identifieur interne : 000312 ( Pmc/Curation ); précédent : 000311; suivant : 000313Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials
Auteurs : Joachim Sieper [Allemagne] ; Benjamin Porter-Brown [Royaume-Uni] ; Liz Thompson [Royaume-Uni] ; Olivier Harari [Royaume-Uni] ; Maxime Dougados [France]Source :
- Annals of the Rheumatic Diseases [ 0003-4967 ] ; 2013.
Abstract
BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS).
BUILDER-1 was a two part, phase II–III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP).
102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found.
BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.
NCT01209702 and NCT01209689 (www.clinicaltrials.gov).
Url:
DOI: 10.1136/annrheumdis-2013-203559
PubMed: 23765873
PubMed Central: 3888605
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials</title><author><name sortKey="Sieper, Joachim" sort="Sieper, Joachim" uniqKey="Sieper J" first="Joachim" last="Sieper">Joachim Sieper</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Medicine 1, Rheumatology</addr-line>,<institution>Charité Universitätsmedizin</institution>,<addr-line>Berlin</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Porter Brown, Benjamin" sort="Porter Brown, Benjamin" uniqKey="Porter Brown B" first="Benjamin" last="Porter-Brown">Benjamin Porter-Brown</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Roche</institution>,<addr-line>Welwyn Garden City</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="Thompson, Liz" sort="Thompson, Liz" uniqKey="Thompson L" first="Liz" last="Thompson">Liz Thompson</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Roche</institution>,<addr-line>Welwyn Garden City</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="Harari, Olivier" sort="Harari, Olivier" uniqKey="Harari O" first="Olivier" last="Harari">Olivier Harari</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Roche</institution>,<addr-line>Welwyn Garden City</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="Dougados, Maxime" sort="Dougados, Maxime" uniqKey="Dougados M" first="Maxime" last="Dougados">Maxime Dougados</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Department of Rheumatology B</addr-line>,<institution>René Descartes University-Paris 5 and Cochin Hospital</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23765873</idno><idno type="pmc">3888605</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888605</idno><idno type="RBID">PMC:3888605</idno><idno type="doi">10.1136/annrheumdis-2013-203559</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000312</idno><idno type="wicri:Area/Pmc/Curation">000312</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials</title><author><name sortKey="Sieper, Joachim" sort="Sieper, Joachim" uniqKey="Sieper J" first="Joachim" last="Sieper">Joachim Sieper</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Medicine 1, Rheumatology</addr-line>,<institution>Charité Universitätsmedizin</institution>,<addr-line>Berlin</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Porter Brown, Benjamin" sort="Porter Brown, Benjamin" uniqKey="Porter Brown B" first="Benjamin" last="Porter-Brown">Benjamin Porter-Brown</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Roche</institution>,<addr-line>Welwyn Garden City</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="Thompson, Liz" sort="Thompson, Liz" uniqKey="Thompson L" first="Liz" last="Thompson">Liz Thompson</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Roche</institution>,<addr-line>Welwyn Garden City</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="Harari, Olivier" sort="Harari, Olivier" uniqKey="Harari O" first="Olivier" last="Harari">Olivier Harari</name><affiliation wicri:level="1"><nlm:aff id="af2"><institution>Roche</institution>,<addr-line>Welwyn Garden City</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="Dougados, Maxime" sort="Dougados, Maxime" uniqKey="Dougados M" first="Maxime" last="Dougados">Maxime Dougados</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Department of Rheumatology B</addr-line>,<institution>René Descartes University-Paris 5 and Cochin Hospital</institution>,<addr-line>Paris</addr-line>,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Annals of the Rheumatic Diseases</title><idno type="ISSN">0003-4967</idno><idno type="eISSN">1468-2060</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objectives</title><p>BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS).</p></sec><sec><title>Methods</title><p>BUILDER-1 was a two part, phase II–III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP).</p></sec><sec><title>Results</title><p>102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found.</p></sec><sec><title>Conclusions</title><p>BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.</p></sec><sec><title>Clinical trial registration numbers:</title><p>NCT01209702 and NCT01209689 (www.clinicaltrials.gov).</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tam, Ls" uniqKey="Tam L">LS Tam</name></author><author><name sortKey="Gu, J" uniqKey="Gu J">J Gu</name></author><author><name sortKey="Yu, D" uniqKey="Yu D">D Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rosenbaum, J" uniqKey="Rosenbaum J">J Rosenbaum</name></author><author><name sortKey="Chandran, V" uniqKey="Chandran V">V Chandran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akkoc, N" uniqKey="Akkoc N">N Akkoc</name></author><author><name sortKey="Khan, Ma" uniqKey="Khan M">MA Khan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Braun, J" uniqKey="Braun J">J Braun</name></author><author><name sortKey="Van Den Berg, R" uniqKey="Van Den Berg R">R van den Berg</name></author><author><name sortKey="Baraliakos, X" uniqKey="Baraliakos X">X Baraliakos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zochling, J" uniqKey="Zochling J">J Zochling</name></author><author><name sortKey="Bohl Buhler, Mh" uniqKey="Bohl Buhler M">MH Bohl-Buhler</name></author><author><name sortKey="Baraliakos, X" uniqKey="Baraliakos X">X Baraliakos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roychowdhury, B" uniqKey="Roychowdhury B">B Roychowdhury</name></author><author><name sortKey="Bintley Bagot, S" uniqKey="Bintley Bagot S">S Bintley-Bagot</name></author><author><name sortKey="Bulgen, Dy" uniqKey="Bulgen D">DY Bulgen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Altan, L" uniqKey="Altan L">L Altan</name></author><author><name sortKey="Bingol, U" uniqKey="Bingol U">U Bingol</name></author><author><name sortKey="Karakoc, Y" uniqKey="Karakoc Y">Y Karakoc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Braun, J" uniqKey="Braun J">J Braun</name></author><author><name sortKey="Baraliakos, X" uniqKey="Baraliakos X">X Baraliakos</name></author><author><name sortKey="Godolias, G" uniqKey="Godolias G">G Godolias</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Inman, Rd" uniqKey="Inman R">RD Inman</name></author><author><name sortKey="Davis, Jc" uniqKey="Davis J">JC Davis</name></author><author><name sortKey="Heijde, D" uniqKey="Heijde D">D Heijde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Braun, J" uniqKey="Braun J">J Braun</name></author><author><name sortKey="Brandt, J" uniqKey="Brandt J">J Brandt</name></author><author><name sortKey="Listing, J" uniqKey="Listing J">J Listing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brandt, J" uniqKey="Brandt J">J Brandt</name></author><author><name sortKey="Khariouzov, A" uniqKey="Khariouzov A">A Khariouzov</name></author><author><name sortKey="Listing, J" uniqKey="Listing J">J Listing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D Van Der Heijde</name></author><author><name sortKey="Schiff, Mh" uniqKey="Schiff M">MH Schiff</name></author><author><name sortKey="Sieper, J" uniqKey="Sieper J">J Sieper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D Van Der Heijde</name></author><author><name sortKey="Kivitz, A" uniqKey="Kivitz A">A Kivitz</name></author><author><name sortKey="Schiff, Mh" uniqKey="Schiff M">MH Schiff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davis, Jc" uniqKey="Davis J">JC Davis</name></author><author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D Van Der Heijde</name></author><author><name sortKey="Braun, J" uniqKey="Braun J">J Braun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D Van Der Heijde</name></author><author><name sortKey="Dijkmans, B" uniqKey="Dijkmans B">B Dijkmans</name></author><author><name sortKey="Geusens, P" uniqKey="Geusens P">P Geusens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rudwaleit, M" uniqKey="Rudwaleit M">M Rudwaleit</name></author><author><name sortKey="Claudepierre, P" uniqKey="Claudepierre P">P Claudepierre</name></author><author><name sortKey="Wordsworth, P" uniqKey="Wordsworth P">P Wordsworth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D Van Der Heijde</name></author><author><name sortKey="Landewe, R" uniqKey="Landewe R">R Landewe</name></author><author><name sortKey="Baraliakos, X" uniqKey="Baraliakos X">X Baraliakos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gratacos, J" uniqKey="Gratacos J">J Gratacos</name></author><author><name sortKey="Collado, A" uniqKey="Collado A">A Collado</name></author><author><name sortKey="Filella, X" uniqKey="Filella X">X Filella</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gratacos, J" uniqKey="Gratacos J">J Gratacos</name></author><author><name sortKey="Collado, A" uniqKey="Collado A">A Collado</name></author><author><name sortKey="Pons, F" uniqKey="Pons F">F Pons</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falkenbach, A" uniqKey="Falkenbach A">A Falkenbach</name></author><author><name sortKey="Herold, M" uniqKey="Herold M">M Herold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bal, A" uniqKey="Bal A">A Bal</name></author><author><name sortKey="Unlu, E" uniqKey="Unlu E">E Unlu</name></author><author><name sortKey="Bahar, G" uniqKey="Bahar G">G Bahar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tutuncu, Zn" uniqKey="Tutuncu Z">ZN Tutuncu</name></author><author><name sortKey="Bilgie, A" uniqKey="Bilgie A">A Bilgie</name></author><author><name sortKey="Kennedy, Lg" uniqKey="Kennedy L">LG Kennedy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Visvanathan, S" uniqKey="Visvanathan S">S Visvanathan</name></author><author><name sortKey="Wagner, C" uniqKey="Wagner C">C Wagner</name></author><author><name sortKey="Marini, Jc" uniqKey="Marini J">JC Marini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Visvanathan, S" uniqKey="Visvanathan S">S Visvanathan</name></author><author><name sortKey="Van Der Heijde, D" uniqKey="Van Der Heijde D">D Van Der Heijde</name></author><author><name sortKey="Deodhar, A" uniqKey="Deodhar A">A Deodhar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mihara, M" uniqKey="Mihara M">M Mihara</name></author><author><name sortKey="Kasutani, K" uniqKey="Kasutani K">K Kasutani</name></author><author><name sortKey="Okazaki, M" uniqKey="Okazaki M">M Okazaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emery, P" uniqKey="Emery P">P Emery</name></author><author><name sortKey="Keystone, E" uniqKey="Keystone E">E Keystone</name></author><author><name sortKey="Tony, Hp" uniqKey="Tony H">HP Tony</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, G" uniqKey="Jones G">G Jones</name></author><author><name sortKey="Sebba, A" uniqKey="Sebba A">A Sebba</name></author><author><name sortKey="Gu, J" uniqKey="Gu J">J Gu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smolen, Js" uniqKey="Smolen J">JS Smolen</name></author><author><name sortKey="Beaulieu, A" uniqKey="Beaulieu A">A Beaulieu</name></author><author><name sortKey="Rubbert Roth, A" uniqKey="Rubbert Roth A">A Rubbert-Roth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Genovese, Mc" uniqKey="Genovese M">MC Genovese</name></author><author><name sortKey="Mckay, Jd" uniqKey="Mckay J">JD McKay</name></author><author><name sortKey="Nasonov, El" uniqKey="Nasonov E">EL Nasonov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kremer, Jm" uniqKey="Kremer J">JM Kremer</name></author><author><name sortKey="Blanco, R" uniqKey="Blanco R">R Blanco</name></author><author><name sortKey="Brzosko, S" uniqKey="Brzosko S">S Brzosko</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Van Der Linden, S" uniqKey="Van Der Linden S">S van der Linden</name></author><author><name sortKey="Valkenburg, Ha" uniqKey="Valkenburg H">HA Valkenburg</name></author><author><name sortKey="Cats, A" uniqKey="Cats A">A Cats</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brulhart, L" uniqKey="Brulhart L">L Brulhart</name></author><author><name sortKey="Nissen, Mj" uniqKey="Nissen M">MJ Nissen</name></author><author><name sortKey="Chevallier, P" uniqKey="Chevallier P">P Chevallier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Henes, Jc" uniqKey="Henes J">JC Henes</name></author><author><name sortKey="Horger, M" uniqKey="Horger M">M Horger</name></author><author><name sortKey="Guenaydin, I" uniqKey="Guenaydin I">I Guenaydin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shima, Y" uniqKey="Shima Y">Y Shima</name></author><author><name sortKey="Tomita, T" uniqKey="Tomita T">T Tomita</name></author><author><name sortKey="Ishii, T" uniqKey="Ishii T">T Ishii</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, Jd" uniqKey="Cohen J">JD Cohen</name></author><author><name sortKey="Ferreira, R" uniqKey="Ferreira R">R Ferreira</name></author><author><name sortKey="Jorgensen, C" uniqKey="Jorgensen C">C Jorgensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dudler, J" uniqKey="Dudler J">J Dudler</name></author><author><name sortKey="Aubry Rozier, B" uniqKey="Aubry Rozier B">B Aubry-Rozier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Del Castillo Pi Ol, N" uniqKey="Del Castillo Pi Ol N">N Del Castillo Piñol</name></author><author><name sortKey="Gossec, L" uniqKey="Gossec L">L Gossec</name></author><author><name sortKey="Sparsa, L" uniqKey="Sparsa L">L Sparsa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haibel, H" uniqKey="Haibel H">H Haibel</name></author><author><name sortKey="Rudwaleit, M" uniqKey="Rudwaleit M">M Rudwaleit</name></author><author><name sortKey="Listing, J" uniqKey="Listing J">J Listing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, Ih" uniqKey="Song I">IH Song</name></author><author><name sortKey="Heldmann, F" uniqKey="Heldmann F">F Heldmann</name></author><author><name sortKey="Rudwaleit, M" uniqKey="Rudwaleit M">M Rudwaleit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Mc" uniqKey="Park M">MC Park</name></author><author><name sortKey="Lee, Sw" uniqKey="Lee S">SW Lee</name></author><author><name sortKey="Choi, St" uniqKey="Choi S">ST Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sieper, J" uniqKey="Sieper J">J Sieper</name></author><author><name sortKey="Inman, Rd" uniqKey="Inman R">RD Inman</name></author><author><name sortKey="Badalamente, S" uniqKey="Badalamente S">S Badalamente</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schiff, Mh" uniqKey="Schiff M">MH Schiff</name></author><author><name sortKey="Kremer, Jm" uniqKey="Kremer J">JM Kremer</name></author><author><name sortKey="Jahreis, A" uniqKey="Jahreis A">A Jahreis</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Rheum Dis</journal-id><journal-id journal-id-type="iso-abbrev">Ann. Rheum. Dis</journal-id><journal-id journal-id-type="hwp">annrheumdis</journal-id><journal-id journal-id-type="publisher-id">ard</journal-id><journal-title-group><journal-title>Annals of the Rheumatic Diseases</journal-title></journal-title-group><issn pub-type="ppub">0003-4967</issn><issn pub-type="epub">1468-2060</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">23765873</article-id><article-id pub-id-type="pmc">3888605</article-id><article-id pub-id-type="publisher-id">annrheumdis-2013-203559</article-id><article-id pub-id-type="doi">10.1136/annrheumdis-2013-203559</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject></subj-group><subj-group subj-group-type="heading"><subject>Clinical and Epidemiological Research</subject></subj-group><series-title>Extended report</series-title></article-categories><title-group><article-title>Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sieper</surname><given-names>Joachim</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Porter-Brown</surname><given-names>Benjamin</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Thompson</surname><given-names>Liz</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Harari</surname><given-names>Olivier</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dougados</surname><given-names>Maxime</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Department of Medicine 1, Rheumatology</addr-line>,<institution>Charité Universitätsmedizin</institution>,<addr-line>Berlin</addr-line>,<country>Germany</country></aff><aff id="af2"><label>2</label><institution>Roche</institution>,<addr-line>Welwyn Garden City</addr-line>,<country>UK</country></aff><aff id="af3"><label>3</label><addr-line>Department of Rheumatology B</addr-line>,<institution>René Descartes University-Paris 5 and Cochin Hospital</institution>,<addr-line>Paris</addr-line>,<country>France</country></aff><author-notes><fn><p><bold>Handling editor</bold> Tore K Kvien</p></fn><corresp><label>Correspondence to</label> Professor Joachim Sieper, Department of Medicine 1, Rheumatology, Charité Universitätsmedizin–Campus Benjamin Franklin, Hindenburgdamm 30, Berlin 12200, Germany; <email>Joachim.sieper@charite.de</email></corresp></author-notes><pub-date pub-type="ppub"><month>1</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>13</day><month>6</month><year>2013</year></pub-date><volume>73</volume><issue>1</issue><fpage>95</fpage><lpage>100</lpage><history><date date-type="accepted"><day>12</day><month>5</month><year>2013</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement><copyright-year>2014</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 3.0) 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 and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link></license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="annrheumdis-2013-203559.pdf"></self-uri><abstract><sec><title>Objectives</title><p>BUILDER-1 and BUILDER-2 aimed to assess the efficacy and safety of tocilizumab (TCZ) in patients with ankylosing spondylitis (AS).</p></sec><sec><title>Methods</title><p>BUILDER-1 was a two part, phase II–III parallel-group trial in patients with AS naive to antitumour necrosis factor (aTNF) treatment. Patients in part 1 received TCZ 8 mg/kg or placebo for 12 weeks. In part 2 (beginning after part 1 enrolment ended), newly enrolled patients received TCZ 4 or 8 mg/kg or placebo for 24 weeks. The same treatment arms were used in BUILDER-2, a phase III study in aTNF-inadequate responders. The primary endpoint for both studies was the proportion of patients achieving 20% improvement in the Assessments in Axial SpondyloArthritis international Society (ASAS). Secondary and exploratory endpoints included ASAS40 response rates, Bath Ankylosing Spondylitis Disease Activity Index improvement, changes in joint counts, enthesitis score and C reactive protein (CRP).</p></sec><sec><title>Results</title><p>102 patients were randomised in BUILDER-1 part 1; 99 (48 TCZ, 51 placebo) completed 12 weeks. Week 12 ASAS20 response rates were 37.3% and 27.5% in the TCZ and placebo arms, respectively (p=0.2823). Secondary and exploratory endpoints did not differ between treatment arms. CRP levels declined with TCZ treatment, suggesting adequate IL-6 receptor blockade. As a result, BUILDER-1 part 2 and BUILDER-2 were terminated. TCZ safety results were consistent with previous observations in rheumatoid arthritis, except for a cluster of anaphylactic and hypersensitivity events at Bulgarian study sites. No apparent explanation for this clustering could be found.</p></sec><sec><title>Conclusions</title><p>BUILDER-1 failed to demonstrate TCZ efficacy in treating aTNF-naive patients with AS.</p></sec><sec><title>Clinical trial registration numbers:</title><p>NCT01209702 and NCT01209689 (www.clinicaltrials.gov).</p></sec></abstract><kwd-group><kwd>Ankylosing Spondylitis</kwd><kwd>Treatment</kwd><kwd>Inflammation</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></record>Pour manipuler ce document sous Unix (Dilib)
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