The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)
Objectives. Clinical response to TNF-α blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response. Methods. Fifty-one patients...
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| Veröffentlicht in: | Rheumatology (Oxford, England) England), 2008-10, Vol.47 (10), p.1469-1475 |
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| creator | Buch, M. H. Reece, R. J. Quinn, M. A. English, A. Cunnane, G. Henshaw, K. Bingham, S. J. Bejarano, V. Isaacs, J. Emery, P. |
| description | Objectives. Clinical response to TNF-α blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response. Methods. Fifty-one patients had arthroscopic biopsies of the knee joint prior to infliximab (3 mg/kg) treatment. Synovial tissue cell numbers (CD68 and CD3 positive) and cytokine expression (TNF-α, lymphotoxin-α, IL-1α, -β and receptor antagonist, and IL-6) pre-treatment was assessed using semi-quantitative immunohistochemistry. Changes in these parameters were assessed 16 weeks after infliximab in 32 patients who underwent repeat arthroscopic biopsy. Results. Of the total patients, 47% (n = 24) achieved an ACR20 response; 53% (n = 27) did not. Baseline synovial TNF-α, IL-1α and -β expression did not differ between the two groups. No differences in baseline TNF-α levels were observed with ACR levels of response (ACR20 and ACR50/70 groups). Post-treatment biopsies (17 ACR responders, 15 ACR non-responders) revealed significant reductions in sub-lining layer TNF-α expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders ( |
| doi_str_mv | 10.1093/rheumatology/ken261 |
| format | Article |
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H. ; Reece, R. J. ; Quinn, M. A. ; English, A. ; Cunnane, G. ; Henshaw, K. ; Bingham, S. J. ; Bejarano, V. ; Isaacs, J. ; Emery, P.</creator><creatorcontrib>Buch, M. H. ; Reece, R. J. ; Quinn, M. A. ; English, A. ; Cunnane, G. ; Henshaw, K. ; Bingham, S. J. ; Bejarano, V. ; Isaacs, J. ; Emery, P.</creatorcontrib><description>Objectives. Clinical response to TNF-α blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response. Methods. Fifty-one patients had arthroscopic biopsies of the knee joint prior to infliximab (3 mg/kg) treatment. Synovial tissue cell numbers (CD68 and CD3 positive) and cytokine expression (TNF-α, lymphotoxin-α, IL-1α, -β and receptor antagonist, and IL-6) pre-treatment was assessed using semi-quantitative immunohistochemistry. Changes in these parameters were assessed 16 weeks after infliximab in 32 patients who underwent repeat arthroscopic biopsy. Results. Of the total patients, 47% (n = 24) achieved an ACR20 response; 53% (n = 27) did not. Baseline synovial TNF-α, IL-1α and -β expression did not differ between the two groups. No differences in baseline TNF-α levels were observed with ACR levels of response (ACR20 and ACR50/70 groups). Post-treatment biopsies (17 ACR responders, 15 ACR non-responders) revealed significant reductions in sub-lining layer TNF-α expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders (<20% CRP suppression) demonstrated no reduction in any of the parameters. Conclusion. Pre-treatment synovial TNF-α or IL-1 expression does not predict TNF blockade response. Both ACR response and non-response was associated with reduction in synovial TNF-α-level expression. Suppression in TNF-α levels was not observed in the worst non-responders. The improvements (including in vascularity), independent of ACR clinical response, are compatible with the reduced structural damage documented in all groups of patients independent of response.</description><identifier>ISSN: 1462-0324</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/ken261</identifier><identifier>PMID: 18660510</identifier><identifier>CODEN: BJRHDF</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Antibodies, Monoclonal - therapeutic use ; Antirheumatic Agents - therapeutic use ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - metabolism ; Arthritis, Rheumatoid - pathology ; Arthroscopy ; Biological and medical sciences ; Biomarkers - metabolism ; Biopsy ; Cytokine ; Cytokines - metabolism ; Diseases of the osteoarticular system ; Female ; Follow-Up Studies ; Humans ; Immunomodulators ; Inflammatory joint diseases ; Infliximab ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Prognosis ; Rheumatoid arthritis ; Severity of Illness Index ; Synovial biopsy ; Synovial Membrane - metabolism ; Synovial Membrane - pathology ; Treatment Outcome ; Tumor Necrosis Factor-alpha - antagonists & inhibitors ; Tumor Necrosis Factor-alpha - metabolism ; Tumour necrosis factor</subject><ispartof>Rheumatology (Oxford, England), 2008-10, Vol.47 (10), p.1469-1475</ispartof><rights>The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2008</rights><rights>2008 INIST-CNRS</rights><rights>The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-68901e65bf0d4070a0e99f3bf2c64f06a38b362a5bbcb3bb06b663ac2d880d663</citedby><cites>FETCH-LOGICAL-c482t-68901e65bf0d4070a0e99f3bf2c64f06a38b362a5bbcb3bb06b663ac2d880d663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20759184$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18660510$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Buch, M. H.</creatorcontrib><creatorcontrib>Reece, R. J.</creatorcontrib><creatorcontrib>Quinn, M. A.</creatorcontrib><creatorcontrib>English, A.</creatorcontrib><creatorcontrib>Cunnane, G.</creatorcontrib><creatorcontrib>Henshaw, K.</creatorcontrib><creatorcontrib>Bingham, S. J.</creatorcontrib><creatorcontrib>Bejarano, V.</creatorcontrib><creatorcontrib>Isaacs, J.</creatorcontrib><creatorcontrib>Emery, P.</creatorcontrib><title>The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)</title><title>Rheumatology (Oxford, England)</title><addtitle>Rheumatology (Oxford)</addtitle><description>Objectives. Clinical response to TNF-α blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response. Methods. Fifty-one patients had arthroscopic biopsies of the knee joint prior to infliximab (3 mg/kg) treatment. Synovial tissue cell numbers (CD68 and CD3 positive) and cytokine expression (TNF-α, lymphotoxin-α, IL-1α, -β and receptor antagonist, and IL-6) pre-treatment was assessed using semi-quantitative immunohistochemistry. Changes in these parameters were assessed 16 weeks after infliximab in 32 patients who underwent repeat arthroscopic biopsy. Results. Of the total patients, 47% (n = 24) achieved an ACR20 response; 53% (n = 27) did not. Baseline synovial TNF-α, IL-1α and -β expression did not differ between the two groups. No differences in baseline TNF-α levels were observed with ACR levels of response (ACR20 and ACR50/70 groups). Post-treatment biopsies (17 ACR responders, 15 ACR non-responders) revealed significant reductions in sub-lining layer TNF-α expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders (<20% CRP suppression) demonstrated no reduction in any of the parameters. Conclusion. Pre-treatment synovial TNF-α or IL-1 expression does not predict TNF blockade response. Both ACR response and non-response was associated with reduction in synovial TNF-α-level expression. Suppression in TNF-α levels was not observed in the worst non-responders. The improvements (including in vascularity), independent of ACR clinical response, are compatible with the reduced structural damage documented in all groups of patients independent of response.</description><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Arthroscopy</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Biopsy</subject><subject>Cytokine</subject><subject>Cytokines - metabolism</subject><subject>Diseases of the osteoarticular system</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Inflammatory joint diseases</subject><subject>Infliximab</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>Rheumatoid arthritis</subject><subject>Severity of Illness Index</subject><subject>Synovial biopsy</subject><subject>Synovial Membrane - metabolism</subject><subject>Synovial Membrane - pathology</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumour necrosis factor</subject><issn>1462-0324</issn><issn>1462-0332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkMFu1DAQhiMEoqXwBEjIQkKCQ9qxnTjJEQqliGq5LFLFxbIde-tu1g62U23eHldZLRw5zX_4_pnRVxSvMZxj6OhFuNPTTiQ_-M18sdWOMPykOMUVIyVQSp4eM6lOihcx3gNAjWn7vDjBLWM5w2mR1ncaPYhh0sgbFGfnH6wYkJqT31qnkd6PQcdovUPWoZx7q5J1G5RyTw3WWZXxjIzeRY2SR-vVFRIuiY13NqZHLohxRu-tM4Pd252QH14Wz4wYon51mGfFz6sv68vr8ubH12-XH29KVbUklaztAGtWSwN9BQ0I0F1nqDREscoAE7SVlBFRS6kklRKYZIwKRfq2hT7Hs-LtsncM_vekY-L3fgoun-S4q1lddxVkiC6QCj7GoA0fQ_4yzBwDfxTN_xXNF9G59eawepI73f_tHMxm4N0BEDErMkE4ZeORI9DUHW6rzJ0vnJ_G_7xcLoVsV--PFRG2nDW0qfn17S8On6rV98_Nit_SP2GlrI0</recordid><startdate>20081001</startdate><enddate>20081001</enddate><creator>Buch, M. H.</creator><creator>Reece, R. J.</creator><creator>Quinn, M. A.</creator><creator>English, A.</creator><creator>Cunnane, G.</creator><creator>Henshaw, K.</creator><creator>Bingham, S. J.</creator><creator>Bejarano, V.</creator><creator>Isaacs, J.</creator><creator>Emery, P.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20081001</creationdate><title>The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)</title><author>Buch, M. H. ; Reece, R. J. ; Quinn, M. A. ; English, A. ; Cunnane, G. ; Henshaw, K. ; Bingham, S. J. ; Bejarano, V. ; Isaacs, J. ; Emery, P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-68901e65bf0d4070a0e99f3bf2c64f06a38b362a5bbcb3bb06b663ac2d880d663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antirheumatic Agents - therapeutic use</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Arthroscopy</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - metabolism</topic><topic>Biopsy</topic><topic>Cytokine</topic><topic>Cytokines - metabolism</topic><topic>Diseases of the osteoarticular system</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Inflammatory joint diseases</topic><topic>Infliximab</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>Rheumatoid arthritis</topic><topic>Severity of Illness Index</topic><topic>Synovial biopsy</topic><topic>Synovial Membrane - metabolism</topic><topic>Synovial Membrane - pathology</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumour necrosis factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Buch, M. H.</creatorcontrib><creatorcontrib>Reece, R. J.</creatorcontrib><creatorcontrib>Quinn, M. A.</creatorcontrib><creatorcontrib>English, A.</creatorcontrib><creatorcontrib>Cunnane, G.</creatorcontrib><creatorcontrib>Henshaw, K.</creatorcontrib><creatorcontrib>Bingham, S. J.</creatorcontrib><creatorcontrib>Bejarano, V.</creatorcontrib><creatorcontrib>Isaacs, J.</creatorcontrib><creatorcontrib>Emery, P.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Buch, M. H.</au><au>Reece, R. J.</au><au>Quinn, M. A.</au><au>English, A.</au><au>Cunnane, G.</au><au>Henshaw, K.</au><au>Bingham, S. J.</au><au>Bejarano, V.</au><au>Isaacs, J.</au><au>Emery, P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2008-10-01</date><risdate>2008</risdate><volume>47</volume><issue>10</issue><spage>1469</spage><epage>1475</epage><pages>1469-1475</pages><issn>1462-0324</issn><eissn>1462-0332</eissn><coden>BJRHDF</coden><abstract>Objectives. Clinical response to TNF-α blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response. Methods. Fifty-one patients had arthroscopic biopsies of the knee joint prior to infliximab (3 mg/kg) treatment. Synovial tissue cell numbers (CD68 and CD3 positive) and cytokine expression (TNF-α, lymphotoxin-α, IL-1α, -β and receptor antagonist, and IL-6) pre-treatment was assessed using semi-quantitative immunohistochemistry. Changes in these parameters were assessed 16 weeks after infliximab in 32 patients who underwent repeat arthroscopic biopsy. Results. Of the total patients, 47% (n = 24) achieved an ACR20 response; 53% (n = 27) did not. Baseline synovial TNF-α, IL-1α and -β expression did not differ between the two groups. No differences in baseline TNF-α levels were observed with ACR levels of response (ACR20 and ACR50/70 groups). Post-treatment biopsies (17 ACR responders, 15 ACR non-responders) revealed significant reductions in sub-lining layer TNF-α expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders (<20% CRP suppression) demonstrated no reduction in any of the parameters. Conclusion. Pre-treatment synovial TNF-α or IL-1 expression does not predict TNF blockade response. Both ACR response and non-response was associated with reduction in synovial TNF-α-level expression. Suppression in TNF-α levels was not observed in the worst non-responders. The improvements (including in vascularity), independent of ACR clinical response, are compatible with the reduced structural damage documented in all groups of patients independent of response.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>18660510</pmid><doi>10.1093/rheumatology/ken261</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies, Monoclonal - therapeutic use Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - metabolism Arthritis, Rheumatoid - pathology Arthroscopy Biological and medical sciences Biomarkers - metabolism Biopsy Cytokine Cytokines - metabolism Diseases of the osteoarticular system Female Follow-Up Studies Humans Immunomodulators Inflammatory joint diseases Infliximab Male Medical sciences Middle Aged Pharmacology. Drug treatments Prognosis Rheumatoid arthritis Severity of Illness Index Synovial biopsy Synovial Membrane - metabolism Synovial Membrane - pathology Treatment Outcome Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - metabolism Tumour necrosis factor |
| title | The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab) |
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