FRI0304 Treatment of knee osteoarthritis with intra-articular infliximab improves total womac score. High baseline levels of synovial cellularity predict improvement
Background Synovial tissue from patients with osteoarthritis (OA) demonstrated synovial inflammation (Benito et al.). We hypothesized that a single intraarticular (IA) injection of an anti-TNF drug would result in decreased inflammatory cell infiltration and ultimately reduce articular injury. Objec...
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| Veröffentlicht in: | Annals of the rheumatic diseases 2013-06, Vol.71 (Suppl 3), p.417-417 |
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| description | Background Synovial tissue from patients with osteoarthritis (OA) demonstrated synovial inflammation (Benito et al.). We hypothesized that a single intraarticular (IA) injection of an anti-TNF drug would result in decreased inflammatory cell infiltration and ultimately reduce articular injury. Objectives Evaluate the short-term benefit of IA anti-TNF therapy in knee osteoarthritis. Methods This study was a single center, 2:1:1 [INF:MP:P] randomization, double-blind, placebo-controlled treatment of knee OA with IA treatments of infliximab (INF) 100 mg, methylprednisolone (MP) 80 mg or saline (P) on Day 0. Subjects (n=16) had to have knee pain and show minimal to moderate osteoarthritic change on plain radiographs. Closed needle synovial biopsies (Bx) were obtained on Days 0 and 28. Total WOMAC was determined at Days 0, 14, 28 and 56. Bivariate associations were investigated using logistic and linear regression. Results Total WOMAC score improved significantly only for Group INF, comparing baseline to Day 56 (p |
| doi_str_mv | 10.1136/annrheumdis-2012-eular.2761 |
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High baseline levels of synovial cellularity predict improvement</title><source>BMJ Journals - NESLi2</source><creator>Lindsley, H.B. ; Schue, J. ; Tawfik, O. ; Bolce, R. ; Smith, D.D. ; Hinson, G. ; Wick, J.A.</creator><creatorcontrib>Lindsley, H.B. ; Schue, J. ; Tawfik, O. ; Bolce, R. ; Smith, D.D. ; Hinson, G. ; Wick, J.A.</creatorcontrib><description>Background Synovial tissue from patients with osteoarthritis (OA) demonstrated synovial inflammation (Benito et al.). We hypothesized that a single intraarticular (IA) injection of an anti-TNF drug would result in decreased inflammatory cell infiltration and ultimately reduce articular injury. Objectives Evaluate the short-term benefit of IA anti-TNF therapy in knee osteoarthritis. Methods This study was a single center, 2:1:1 [INF:MP:P] randomization, double-blind, placebo-controlled treatment of knee OA with IA treatments of infliximab (INF) 100 mg, methylprednisolone (MP) 80 mg or saline (P) on Day 0. Subjects (n=16) had to have knee pain and show minimal to moderate osteoarthritic change on plain radiographs. Closed needle synovial biopsies (Bx) were obtained on Days 0 and 28. Total WOMAC was determined at Days 0, 14, 28 and 56. Bivariate associations were investigated using logistic and linear regression. Results Total WOMAC score improved significantly only for Group INF, comparing baseline to Day 56 (p<0.05) (See Fig). Overall 6 of 16 subjects had high levels of synovial cellularity (level 1-2, scale 0-3) at baseline, 4 of whom were in Group INF. These 4 subjects had the greatest degree of improvement in total WOMAC. Baseline CRP levels (baseline values =0.57-1.21 mg/dl) correlated with total WOMAC scores and did predict improvement (p=0.07). Baseline knee MRI grade (0-5) correlated with baseline total WOMAC but did not predict improvement. Circulating INF levels showed a maximum median concentration at Day 4 (3.70 ug/ml; range 0.56-11.27); two subjects found to have anti-INF antibodies by Day 14 showed reduced levels of INF at Day 14 (median 0.05 ug/ml), compared to the remaining 6 subjects at Day 14 (2.67 ug/ml; range 0.56-3.77). Synovial tissue showed reduction in two markers: CD68 macrophages (3 of 7 Bx INF Group) and CD54 ICAM-1 (2 of 4 Bx MP Group). Flow cytometric studies of PBMCs at Days 0 and 28 showed reduced numbers of INF subjects with TNF-expressing CD20 B cells and CD14 monocytes at Day 28. Conclusions In this pilot study the Total WOMAC score showed significant improvement by Day 56 (p<0.05) for the INF group. Baseline synovial cellularity and CRP also correlated with improvement. Anti-TNF IA therapy offers promise as symptomatic therapy. References Benito MJ, et al. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005;64:1263-7. Disclosure of Interest H. Lindsley Grant/Research support from: Janssen, J. Schue: None Declared, O. Tawfik: None Declared, R. Bolce: None Declared, D. Smith: None Declared, G. Hinson: None Declared, J. Wick: None Declared</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2012-eular.2761</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><ispartof>Annals of the rheumatic diseases, 2013-06, Vol.71 (Suppl 3), p.417-417</ispartof><rights>2013, 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</rights><rights>Copyright: 2013 (c) 2013, 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</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b2238-f917de34a614c59e7bdb51af1b0814729ee396d010199f4065499d4b67dd11c93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/71/Suppl_3/417.1.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/71/Suppl_3/417.1.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,3196,23571,27924,27925,77600,77631</link.rule.ids></links><search><creatorcontrib>Lindsley, H.B.</creatorcontrib><creatorcontrib>Schue, J.</creatorcontrib><creatorcontrib>Tawfik, O.</creatorcontrib><creatorcontrib>Bolce, R.</creatorcontrib><creatorcontrib>Smith, D.D.</creatorcontrib><creatorcontrib>Hinson, G.</creatorcontrib><creatorcontrib>Wick, J.A.</creatorcontrib><title>FRI0304 Treatment of knee osteoarthritis with intra-articular infliximab improves total womac score. High baseline levels of synovial cellularity predict improvement</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description>Background Synovial tissue from patients with osteoarthritis (OA) demonstrated synovial inflammation (Benito et al.). We hypothesized that a single intraarticular (IA) injection of an anti-TNF drug would result in decreased inflammatory cell infiltration and ultimately reduce articular injury. Objectives Evaluate the short-term benefit of IA anti-TNF therapy in knee osteoarthritis. Methods This study was a single center, 2:1:1 [INF:MP:P] randomization, double-blind, placebo-controlled treatment of knee OA with IA treatments of infliximab (INF) 100 mg, methylprednisolone (MP) 80 mg or saline (P) on Day 0. Subjects (n=16) had to have knee pain and show minimal to moderate osteoarthritic change on plain radiographs. Closed needle synovial biopsies (Bx) were obtained on Days 0 and 28. Total WOMAC was determined at Days 0, 14, 28 and 56. Bivariate associations were investigated using logistic and linear regression. Results Total WOMAC score improved significantly only for Group INF, comparing baseline to Day 56 (p<0.05) (See Fig). Overall 6 of 16 subjects had high levels of synovial cellularity (level 1-2, scale 0-3) at baseline, 4 of whom were in Group INF. These 4 subjects had the greatest degree of improvement in total WOMAC. Baseline CRP levels (baseline values =0.57-1.21 mg/dl) correlated with total WOMAC scores and did predict improvement (p=0.07). Baseline knee MRI grade (0-5) correlated with baseline total WOMAC but did not predict improvement. Circulating INF levels showed a maximum median concentration at Day 4 (3.70 ug/ml; range 0.56-11.27); two subjects found to have anti-INF antibodies by Day 14 showed reduced levels of INF at Day 14 (median 0.05 ug/ml), compared to the remaining 6 subjects at Day 14 (2.67 ug/ml; range 0.56-3.77). Synovial tissue showed reduction in two markers: CD68 macrophages (3 of 7 Bx INF Group) and CD54 ICAM-1 (2 of 4 Bx MP Group). Flow cytometric studies of PBMCs at Days 0 and 28 showed reduced numbers of INF subjects with TNF-expressing CD20 B cells and CD14 monocytes at Day 28. Conclusions In this pilot study the Total WOMAC score showed significant improvement by Day 56 (p<0.05) for the INF group. Baseline synovial cellularity and CRP also correlated with improvement. Anti-TNF IA therapy offers promise as symptomatic therapy. References Benito MJ, et al. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005;64:1263-7. Disclosure of Interest H. Lindsley Grant/Research support from: Janssen, J. Schue: None Declared, O. Tawfik: None Declared, R. Bolce: None Declared, D. Smith: None Declared, G. Hinson: None Declared, J. Wick: None Declared</description><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqVUc1uEzEQthBIhMI7WOp5g2fXsdfiBBGllUJBUHrgYnl3Z4lT7zrYTtrcuPAsvFefBC8BxJXTaEbfz8x8hJwCmwNU4rkZx7DG3dDZWJQMygJ3zoR5KQU8IDPgos5jwR6SGWOsKrgS8jF5EuMmt6yGekZ-nH24YBXj99--XwU0acAxUd_TmxGR-pjQm5DWwSYb6a1Na2rHFEyRh7advHLfO3tnB9NQO2yD32OkySfj6K0fTEtj6wPO6bn9sqaNiejsiNThHl2cfOJh9Hub0S06NwnadKDbgJ1t0x_Baaen5FFvXMRnv-sJ-XT2-mp5XqzevblYvlwVTVlWddErkB1W3Ajg7UKhbLpmAaaHJp_LZakQKyU6BgyU6jkTC65Uxxshuw6gVdUJOT3qZuevO4xJb_wujNlSg5RSSaF4nVEvjqg2-BgD9nob8gvCQQPTUzL6n2T0lIz-lYyeksns4si2-b93f6km3GghK7nQl9dL_f7tavVZvbrWHzNeHPHNsPkvo5_s6K5V</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>Lindsley, H.B.</creator><creator>Schue, J.</creator><creator>Tawfik, O.</creator><creator>Bolce, R.</creator><creator>Smith, D.D.</creator><creator>Hinson, G.</creator><creator>Wick, J.A.</creator><general>BMJ Publishing Group Ltd and European League Against Rheumatism</general><general>BMJ Publishing Group LTD</general><scope>BSCLL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>201306</creationdate><title>FRI0304 Treatment of knee osteoarthritis with intra-articular infliximab improves total womac score. High baseline levels of synovial cellularity predict improvement</title><author>Lindsley, H.B. ; Schue, J. ; Tawfik, O. ; Bolce, R. ; Smith, D.D. ; Hinson, G. ; Wick, J.A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b2238-f917de34a614c59e7bdb51af1b0814729ee396d010199f4065499d4b67dd11c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lindsley, H.B.</creatorcontrib><creatorcontrib>Schue, J.</creatorcontrib><creatorcontrib>Tawfik, O.</creatorcontrib><creatorcontrib>Bolce, R.</creatorcontrib><creatorcontrib>Smith, D.D.</creatorcontrib><creatorcontrib>Hinson, G.</creatorcontrib><creatorcontrib>Wick, J.A.</creatorcontrib><collection>Istex</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lindsley, H.B.</au><au>Schue, J.</au><au>Tawfik, O.</au><au>Bolce, R.</au><au>Smith, D.D.</au><au>Hinson, G.</au><au>Wick, J.A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FRI0304 Treatment of knee osteoarthritis with intra-articular infliximab improves total womac score. High baseline levels of synovial cellularity predict improvement</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2013-06</date><risdate>2013</risdate><volume>71</volume><issue>Suppl 3</issue><spage>417</spage><epage>417</epage><pages>417-417</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>Background Synovial tissue from patients with osteoarthritis (OA) demonstrated synovial inflammation (Benito et al.). We hypothesized that a single intraarticular (IA) injection of an anti-TNF drug would result in decreased inflammatory cell infiltration and ultimately reduce articular injury. Objectives Evaluate the short-term benefit of IA anti-TNF therapy in knee osteoarthritis. Methods This study was a single center, 2:1:1 [INF:MP:P] randomization, double-blind, placebo-controlled treatment of knee OA with IA treatments of infliximab (INF) 100 mg, methylprednisolone (MP) 80 mg or saline (P) on Day 0. Subjects (n=16) had to have knee pain and show minimal to moderate osteoarthritic change on plain radiographs. Closed needle synovial biopsies (Bx) were obtained on Days 0 and 28. Total WOMAC was determined at Days 0, 14, 28 and 56. Bivariate associations were investigated using logistic and linear regression. Results Total WOMAC score improved significantly only for Group INF, comparing baseline to Day 56 (p<0.05) (See Fig). Overall 6 of 16 subjects had high levels of synovial cellularity (level 1-2, scale 0-3) at baseline, 4 of whom were in Group INF. These 4 subjects had the greatest degree of improvement in total WOMAC. Baseline CRP levels (baseline values =0.57-1.21 mg/dl) correlated with total WOMAC scores and did predict improvement (p=0.07). Baseline knee MRI grade (0-5) correlated with baseline total WOMAC but did not predict improvement. Circulating INF levels showed a maximum median concentration at Day 4 (3.70 ug/ml; range 0.56-11.27); two subjects found to have anti-INF antibodies by Day 14 showed reduced levels of INF at Day 14 (median 0.05 ug/ml), compared to the remaining 6 subjects at Day 14 (2.67 ug/ml; range 0.56-3.77). Synovial tissue showed reduction in two markers: CD68 macrophages (3 of 7 Bx INF Group) and CD54 ICAM-1 (2 of 4 Bx MP Group). Flow cytometric studies of PBMCs at Days 0 and 28 showed reduced numbers of INF subjects with TNF-expressing CD20 B cells and CD14 monocytes at Day 28. Conclusions In this pilot study the Total WOMAC score showed significant improvement by Day 56 (p<0.05) for the INF group. Baseline synovial cellularity and CRP also correlated with improvement. Anti-TNF IA therapy offers promise as symptomatic therapy. References Benito MJ, et al. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005;64:1263-7. Disclosure of Interest H. Lindsley Grant/Research support from: Janssen, J. Schue: None Declared, O. Tawfik: None Declared, R. Bolce: None Declared, D. Smith: None Declared, G. Hinson: None Declared, J. Wick: None Declared</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and European League Against Rheumatism</pub><doi>10.1136/annrheumdis-2012-eular.2761</doi><tpages>1</tpages></addata></record> |
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| title | FRI0304 Treatment of knee osteoarthritis with intra-articular infliximab improves total womac score. High baseline levels of synovial cellularity predict improvement |
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