The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment
Objective To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment. Methods This was a 2‐year, multicenter, double‐blind, active...
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| Veröffentlicht in: | Arthritis and rheumatism 2006-01, Vol.54 (1), p.26-37 |
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| creator | Breedveld, Ferdinand C. Weisman, Michael H. Kavanaugh, Arthur F. Cohen, Stanley B. Pavelka, Karel Vollenhoven, Ronald van Sharp, John Perez, John L. Spencer‐Green, George T. |
| description | Objective
To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment.
Methods
This was a 2‐year, multicenter, double‐blind, active comparator–controlled study of 799 RA patients with active disease of |
| doi_str_mv | 10.1002/art.21519 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_577537</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ART21519</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3619-f8160991e1260b058bfcdc74e4084df7c0c1a3ca8df8e316692d5663bb3e26e93</originalsourceid><addsrcrecordid>eNp1ks9u1DAQxgMC0aVw4MoBzRVp09rxOn96W1VbqFQEWi3nyLEnjSGJI9vZJZx4hD4jT4JpVoAqcZnPM_rNN7Y1UfSKkjNKSHIurD9LKKfF42hBeVLEhDL6JFoQQlYx4wU9iZ479yWkCePsWXRCU5ZznpDFo9e7BuHTdvPherMF50c1XcAaurH1WmLv0S7Bil6ZTn9HtQRlxqrFnz_uqlb3CmSIWooWvNUhmhqk6SrdC69ND75BK4YJDto3IJRodTd2ooKhHR106BvjLX4THmGP1j2sidb0CMb-2znXdA9DmBCu52ZvFLadliBuby06p_cItsHQ4I1WED6nsdrrwDYGGqGgN_5eB4t7bR7ODSp8F8xfRE9r0Tp8edTT6PPVZnf5Pr75-O76cn0TS5bSIq5zmpKioEiTlFSE51UtlcxWuCL5StWZJJIKJkWu6hwZTdMiUTxNWVUxTFIs2GkUz77ugMNYlYPVnbBTaYQuj6Wv4YQlzzLOssC_nXlpjXMW6z8dlJS_96EMTy7v9yGwb2Y2uHSo_pLHBQjA-QwcdIvT_53K9XY3W_4CiIDJkA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Breedveld, Ferdinand C. ; Weisman, Michael H. ; Kavanaugh, Arthur F. ; Cohen, Stanley B. ; Pavelka, Karel ; Vollenhoven, Ronald van ; Sharp, John ; Perez, John L. ; Spencer‐Green, George T.</creator><creatorcontrib>Breedveld, Ferdinand C. ; Weisman, Michael H. ; Kavanaugh, Arthur F. ; Cohen, Stanley B. ; Pavelka, Karel ; Vollenhoven, Ronald van ; Sharp, John ; Perez, John L. ; Spencer‐Green, George T.</creatorcontrib><description>Objective
To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment.
Methods
This was a 2‐year, multicenter, double‐blind, active comparator–controlled study of 799 RA patients with active disease of <3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co‐primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score.
Results
Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P ≤ 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28‐joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups.
Conclusion
In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.</description><identifier>ISSN: 0004-3591</identifier><identifier>EISSN: 1529-0131</identifier><identifier>DOI: 10.1002/art.21519</identifier><identifier>PMID: 16385520</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adalimumab ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents - administration & dosage ; Antirheumatic Agents - adverse effects ; Arthritis, Rheumatoid - drug therapy ; Disease Progression ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Male ; Methotrexate - administration & dosage ; Methotrexate - adverse effects ; Middle Aged ; Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><ispartof>Arthritis and rheumatism, 2006-01, Vol.54 (1), p.26-37</ispartof><rights>Copyright © 2006 by the American College of Rheumatology</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3619-f8160991e1260b058bfcdc74e4084df7c0c1a3ca8df8e316692d5663bb3e26e93</citedby><cites>FETCH-LOGICAL-c3619-f8160991e1260b058bfcdc74e4084df7c0c1a3ca8df8e316692d5663bb3e26e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.21519$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.21519$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,4010,27900,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16385520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1939968$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Breedveld, Ferdinand C.</creatorcontrib><creatorcontrib>Weisman, Michael H.</creatorcontrib><creatorcontrib>Kavanaugh, Arthur F.</creatorcontrib><creatorcontrib>Cohen, Stanley B.</creatorcontrib><creatorcontrib>Pavelka, Karel</creatorcontrib><creatorcontrib>Vollenhoven, Ronald van</creatorcontrib><creatorcontrib>Sharp, John</creatorcontrib><creatorcontrib>Perez, John L.</creatorcontrib><creatorcontrib>Spencer‐Green, George T.</creatorcontrib><title>The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment</title><title>Arthritis and rheumatism</title><addtitle>Arthritis Rheum</addtitle><description>Objective
To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment.
Methods
This was a 2‐year, multicenter, double‐blind, active comparator–controlled study of 799 RA patients with active disease of <3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co‐primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score.
Results
Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P ≤ 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28‐joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups.
Conclusion
In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.</description><subject>Adalimumab</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Antirheumatic Agents - administration & dosage</subject><subject>Antirheumatic Agents - adverse effects</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Disease Progression</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Methotrexate - administration & dosage</subject><subject>Methotrexate - adverse effects</subject><subject>Middle Aged</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><issn>0004-3591</issn><issn>1529-0131</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1ks9u1DAQxgMC0aVw4MoBzRVp09rxOn96W1VbqFQEWi3nyLEnjSGJI9vZJZx4hD4jT4JpVoAqcZnPM_rNN7Y1UfSKkjNKSHIurD9LKKfF42hBeVLEhDL6JFoQQlYx4wU9iZ479yWkCePsWXRCU5ZznpDFo9e7BuHTdvPherMF50c1XcAaurH1WmLv0S7Bil6ZTn9HtQRlxqrFnz_uqlb3CmSIWooWvNUhmhqk6SrdC69ND75BK4YJDto3IJRodTd2ooKhHR106BvjLX4THmGP1j2sidb0CMb-2znXdA9DmBCu52ZvFLadliBuby06p_cItsHQ4I1WED6nsdrrwDYGGqGgN_5eB4t7bR7ODSp8F8xfRE9r0Tp8edTT6PPVZnf5Pr75-O76cn0TS5bSIq5zmpKioEiTlFSE51UtlcxWuCL5StWZJJIKJkWu6hwZTdMiUTxNWVUxTFIs2GkUz77ugMNYlYPVnbBTaYQuj6Wv4YQlzzLOssC_nXlpjXMW6z8dlJS_96EMTy7v9yGwb2Y2uHSo_pLHBQjA-QwcdIvT_53K9XY3W_4CiIDJkA</recordid><startdate>200601</startdate><enddate>200601</enddate><creator>Breedveld, Ferdinand C.</creator><creator>Weisman, Michael H.</creator><creator>Kavanaugh, Arthur F.</creator><creator>Cohen, Stanley B.</creator><creator>Pavelka, Karel</creator><creator>Vollenhoven, Ronald van</creator><creator>Sharp, John</creator><creator>Perez, John L.</creator><creator>Spencer‐Green, George T.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>200601</creationdate><title>The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment</title><author>Breedveld, Ferdinand C. ; Weisman, Michael H. ; Kavanaugh, Arthur F. ; Cohen, Stanley B. ; Pavelka, Karel ; Vollenhoven, Ronald van ; Sharp, John ; Perez, John L. ; Spencer‐Green, George T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3619-f8160991e1260b058bfcdc74e4084df7c0c1a3ca8df8e316692d5663bb3e26e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adalimumab</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Antirheumatic Agents - administration & dosage</topic><topic>Antirheumatic Agents - adverse effects</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Disease Progression</topic><topic>Double-Blind Method</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Methotrexate - administration & dosage</topic><topic>Methotrexate - adverse effects</topic><topic>Middle Aged</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><toplevel>online_resources</toplevel><creatorcontrib>Breedveld, Ferdinand C.</creatorcontrib><creatorcontrib>Weisman, Michael H.</creatorcontrib><creatorcontrib>Kavanaugh, Arthur F.</creatorcontrib><creatorcontrib>Cohen, Stanley B.</creatorcontrib><creatorcontrib>Pavelka, Karel</creatorcontrib><creatorcontrib>Vollenhoven, Ronald van</creatorcontrib><creatorcontrib>Sharp, John</creatorcontrib><creatorcontrib>Perez, John L.</creatorcontrib><creatorcontrib>Spencer‐Green, George T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Breedveld, Ferdinand C.</au><au>Weisman, Michael H.</au><au>Kavanaugh, Arthur F.</au><au>Cohen, Stanley B.</au><au>Pavelka, Karel</au><au>Vollenhoven, Ronald van</au><au>Sharp, John</au><au>Perez, John L.</au><au>Spencer‐Green, George T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment</atitle><jtitle>Arthritis and rheumatism</jtitle><addtitle>Arthritis Rheum</addtitle><date>2006-01</date><risdate>2006</risdate><volume>54</volume><issue>1</issue><spage>26</spage><epage>37</epage><pages>26-37</pages><issn>0004-3591</issn><eissn>1529-0131</eissn><abstract>Objective
To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment.
Methods
This was a 2‐year, multicenter, double‐blind, active comparator–controlled study of 799 RA patients with active disease of <3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co‐primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score.
Results
Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P ≤ 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28‐joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups.
Conclusion
In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>16385520</pmid><doi>10.1002/art.21519</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0004-3591 |
| ispartof | Arthritis and rheumatism, 2006-01, Vol.54 (1), p.26-37 |
| issn | 0004-3591 1529-0131 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_577537 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adalimumab Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal, Humanized Antirheumatic Agents - administration & dosage Antirheumatic Agents - adverse effects Arthritis, Rheumatoid - drug therapy Disease Progression Double-Blind Method Drug Therapy, Combination Female Humans Male Methotrexate - administration & dosage Methotrexate - adverse effects Middle Aged Tumor Necrosis Factor-alpha - antagonists & inhibitors |
| title | The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment |
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