High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients
Summary Background Antibodies to infliximab (ATI) can complicate infliximab (IFX) treatment of inflammatory bowel disease (IBD) patients. Aims To identify a clinically relevant threshold for ATI using a drug‐tolerant assay and to clarify factors for ATI development and their relation to clinical out...
Gespeichert in:
| Veröffentlicht in: | GastroHep 2019-09, Vol.1 (5), p.214-222 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 222 |
|---|---|
| container_issue | 5 |
| container_start_page | 214 |
| container_title | GastroHep |
| container_volume | 1 |
| creator | Tun, Gloria S. Z. Downey, Robert Robinson, Kerry Wright, Alison Marshall, Laura Emsell, Kristina Swallow, Kirsty Wild, Graeme Brooks, Alenka J. Chew, Thean S. Hale, Melissa F. Sargur, Ravishankar Lobo, Alan J. |
| description | Summary
Background
Antibodies to infliximab (ATI) can complicate infliximab (IFX) treatment of inflammatory bowel disease (IBD) patients.
Aims
To identify a clinically relevant threshold for ATI using a drug‐tolerant assay and to clarify factors for ATI development and their relation to clinical outcomes.
Methods
A cohort study of all IBD patients receiving IFX from May 2016 to April 2017 at a tertiary referral centre. Clinical data and serial therapeutic drug monitoring (at every infusion after the first) were collected.
Results
Over 12 months follow‐up, 113/214 (53%) patients had positive ATI, 94/214 (44%) had negative ATI and 7/214 (3%) had transient ATI. Concomitant immunosuppression was negatively associated with ATI positivity: thiopurines OR 0.48, methotrexate OR 0.36. ATI formation was more likely to be preceded by subtherapeutic IFX levels (57%) than vice versa (9%). Positive ATI were significantly associated with infusion reactions, loss of clinical remission and a reduction in IFX levels. In patients positive for ATI at first maintenance dose, 71% were treatment failures by second maintenance dose compared to 28% in those with negative ATI (P |
| doi_str_mv | 10.1002/ygh2.363 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_ygh2_363</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>YGH2363</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1443-2391cfc1d43a3782fb56032d6ac1f224076087b52f5ca9d6e5cc9d8390250afb3</originalsourceid><addsrcrecordid>eNp1kE1LAzEQhoMoWGrBn5Cjl6352M-jFG2Fghc9eFqyyaSNZJOSrNb115u1Hrx4moF53mHmQeiakiUlhN2Ouz1b8pKfoRnNqzqjjDfnf_pLtIjxjSSUUUYKMkNfG7Pb40OAD2HBScBeY-EG03llIOLBY-O0NZ-mF10aKDzswQQcwIrBeDcB0hpnpLDYvw_S9yll3E9K9L0YfBhx549gsTIRRAR8SElwQ7xCF1rYCIvfOkcvD_fPq022fVo_ru62maR5zrN0NpVaUpVzwaua6a4oCWeqFJJqxnJSlaSuuoLpQopGlVBI2aiaN4QVROiOz9HNaa8MPsYAuj2E9E4YW0raSVs7aWuTtoRmJ_RoLIz_cu3resMm_hvJVnCS</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients</title><source>Access via Wiley Online Library</source><creator>Tun, Gloria S. Z. ; Downey, Robert ; Robinson, Kerry ; Wright, Alison ; Marshall, Laura ; Emsell, Kristina ; Swallow, Kirsty ; Wild, Graeme ; Brooks, Alenka J. ; Chew, Thean S. ; Hale, Melissa F. ; Sargur, Ravishankar ; Lobo, Alan J.</creator><creatorcontrib>Tun, Gloria S. Z. ; Downey, Robert ; Robinson, Kerry ; Wright, Alison ; Marshall, Laura ; Emsell, Kristina ; Swallow, Kirsty ; Wild, Graeme ; Brooks, Alenka J. ; Chew, Thean S. ; Hale, Melissa F. ; Sargur, Ravishankar ; Lobo, Alan J.</creatorcontrib><description>Summary
Background
Antibodies to infliximab (ATI) can complicate infliximab (IFX) treatment of inflammatory bowel disease (IBD) patients.
Aims
To identify a clinically relevant threshold for ATI using a drug‐tolerant assay and to clarify factors for ATI development and their relation to clinical outcomes.
Methods
A cohort study of all IBD patients receiving IFX from May 2016 to April 2017 at a tertiary referral centre. Clinical data and serial therapeutic drug monitoring (at every infusion after the first) were collected.
Results
Over 12 months follow‐up, 113/214 (53%) patients had positive ATI, 94/214 (44%) had negative ATI and 7/214 (3%) had transient ATI. Concomitant immunosuppression was negatively associated with ATI positivity: thiopurines OR 0.48, methotrexate OR 0.36. ATI formation was more likely to be preceded by subtherapeutic IFX levels (57%) than vice versa (9%). Positive ATI were significantly associated with infusion reactions, loss of clinical remission and a reduction in IFX levels. In patients positive for ATI at first maintenance dose, 71% were treatment failures by second maintenance dose compared to 28% in those with negative ATI (P < .01). An ATI threshold of 2.5 mg/L had a sensitivity of 0.78 and a specificity of 0.63 in detecting loss of clinical remission ≤8 weeks.
Conclusions
There is a high prevalence of positive ATI and subtherapeutic IFX in IBD patients. Early ATI post induction is associated with a high rate of rapid treatment failure. ATI are significantly associated with loss of clinical remission. A lower ATI threshold of 2.5 mg/L has high sensitivity for loss of clinical remission.</description><identifier>ISSN: 1478-1239</identifier><identifier>EISSN: 1478-1239</identifier><identifier>DOI: 10.1002/ygh2.363</identifier><language>eng</language><subject>Crohn's disease ; inflammatory bowel disease ; infliximab ; ulcerative colitis</subject><ispartof>GastroHep, 2019-09, Vol.1 (5), p.214-222</ispartof><rights>2019 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1443-2391cfc1d43a3782fb56032d6ac1f224076087b52f5ca9d6e5cc9d8390250afb3</citedby><cites>FETCH-LOGICAL-c1443-2391cfc1d43a3782fb56032d6ac1f224076087b52f5ca9d6e5cc9d8390250afb3</cites><orcidid>0000-0003-1551-9174</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fygh2.363$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fygh2.363$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,782,786,1419,27931,27932,45581,45582</link.rule.ids></links><search><creatorcontrib>Tun, Gloria S. Z.</creatorcontrib><creatorcontrib>Downey, Robert</creatorcontrib><creatorcontrib>Robinson, Kerry</creatorcontrib><creatorcontrib>Wright, Alison</creatorcontrib><creatorcontrib>Marshall, Laura</creatorcontrib><creatorcontrib>Emsell, Kristina</creatorcontrib><creatorcontrib>Swallow, Kirsty</creatorcontrib><creatorcontrib>Wild, Graeme</creatorcontrib><creatorcontrib>Brooks, Alenka J.</creatorcontrib><creatorcontrib>Chew, Thean S.</creatorcontrib><creatorcontrib>Hale, Melissa F.</creatorcontrib><creatorcontrib>Sargur, Ravishankar</creatorcontrib><creatorcontrib>Lobo, Alan J.</creatorcontrib><title>High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients</title><title>GastroHep</title><description>Summary
Background
Antibodies to infliximab (ATI) can complicate infliximab (IFX) treatment of inflammatory bowel disease (IBD) patients.
Aims
To identify a clinically relevant threshold for ATI using a drug‐tolerant assay and to clarify factors for ATI development and their relation to clinical outcomes.
Methods
A cohort study of all IBD patients receiving IFX from May 2016 to April 2017 at a tertiary referral centre. Clinical data and serial therapeutic drug monitoring (at every infusion after the first) were collected.
Results
Over 12 months follow‐up, 113/214 (53%) patients had positive ATI, 94/214 (44%) had negative ATI and 7/214 (3%) had transient ATI. Concomitant immunosuppression was negatively associated with ATI positivity: thiopurines OR 0.48, methotrexate OR 0.36. ATI formation was more likely to be preceded by subtherapeutic IFX levels (57%) than vice versa (9%). Positive ATI were significantly associated with infusion reactions, loss of clinical remission and a reduction in IFX levels. In patients positive for ATI at first maintenance dose, 71% were treatment failures by second maintenance dose compared to 28% in those with negative ATI (P < .01). An ATI threshold of 2.5 mg/L had a sensitivity of 0.78 and a specificity of 0.63 in detecting loss of clinical remission ≤8 weeks.
Conclusions
There is a high prevalence of positive ATI and subtherapeutic IFX in IBD patients. Early ATI post induction is associated with a high rate of rapid treatment failure. ATI are significantly associated with loss of clinical remission. A lower ATI threshold of 2.5 mg/L has high sensitivity for loss of clinical remission.</description><subject>Crohn's disease</subject><subject>inflammatory bowel disease</subject><subject>infliximab</subject><subject>ulcerative colitis</subject><issn>1478-1239</issn><issn>1478-1239</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kE1LAzEQhoMoWGrBn5Cjl6352M-jFG2Fghc9eFqyyaSNZJOSrNb115u1Hrx4moF53mHmQeiakiUlhN2Ouz1b8pKfoRnNqzqjjDfnf_pLtIjxjSSUUUYKMkNfG7Pb40OAD2HBScBeY-EG03llIOLBY-O0NZ-mF10aKDzswQQcwIrBeDcB0hpnpLDYvw_S9yll3E9K9L0YfBhx549gsTIRRAR8SElwQ7xCF1rYCIvfOkcvD_fPq022fVo_ru62maR5zrN0NpVaUpVzwaua6a4oCWeqFJJqxnJSlaSuuoLpQopGlVBI2aiaN4QVROiOz9HNaa8MPsYAuj2E9E4YW0raSVs7aWuTtoRmJ_RoLIz_cu3resMm_hvJVnCS</recordid><startdate>201909</startdate><enddate>201909</enddate><creator>Tun, Gloria S. Z.</creator><creator>Downey, Robert</creator><creator>Robinson, Kerry</creator><creator>Wright, Alison</creator><creator>Marshall, Laura</creator><creator>Emsell, Kristina</creator><creator>Swallow, Kirsty</creator><creator>Wild, Graeme</creator><creator>Brooks, Alenka J.</creator><creator>Chew, Thean S.</creator><creator>Hale, Melissa F.</creator><creator>Sargur, Ravishankar</creator><creator>Lobo, Alan J.</creator><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-1551-9174</orcidid></search><sort><creationdate>201909</creationdate><title>High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients</title><author>Tun, Gloria S. Z. ; Downey, Robert ; Robinson, Kerry ; Wright, Alison ; Marshall, Laura ; Emsell, Kristina ; Swallow, Kirsty ; Wild, Graeme ; Brooks, Alenka J. ; Chew, Thean S. ; Hale, Melissa F. ; Sargur, Ravishankar ; Lobo, Alan J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1443-2391cfc1d43a3782fb56032d6ac1f224076087b52f5ca9d6e5cc9d8390250afb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Crohn's disease</topic><topic>inflammatory bowel disease</topic><topic>infliximab</topic><topic>ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tun, Gloria S. Z.</creatorcontrib><creatorcontrib>Downey, Robert</creatorcontrib><creatorcontrib>Robinson, Kerry</creatorcontrib><creatorcontrib>Wright, Alison</creatorcontrib><creatorcontrib>Marshall, Laura</creatorcontrib><creatorcontrib>Emsell, Kristina</creatorcontrib><creatorcontrib>Swallow, Kirsty</creatorcontrib><creatorcontrib>Wild, Graeme</creatorcontrib><creatorcontrib>Brooks, Alenka J.</creatorcontrib><creatorcontrib>Chew, Thean S.</creatorcontrib><creatorcontrib>Hale, Melissa F.</creatorcontrib><creatorcontrib>Sargur, Ravishankar</creatorcontrib><creatorcontrib>Lobo, Alan J.</creatorcontrib><collection>CrossRef</collection><jtitle>GastroHep</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tun, Gloria S. Z.</au><au>Downey, Robert</au><au>Robinson, Kerry</au><au>Wright, Alison</au><au>Marshall, Laura</au><au>Emsell, Kristina</au><au>Swallow, Kirsty</au><au>Wild, Graeme</au><au>Brooks, Alenka J.</au><au>Chew, Thean S.</au><au>Hale, Melissa F.</au><au>Sargur, Ravishankar</au><au>Lobo, Alan J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients</atitle><jtitle>GastroHep</jtitle><date>2019-09</date><risdate>2019</risdate><volume>1</volume><issue>5</issue><spage>214</spage><epage>222</epage><pages>214-222</pages><issn>1478-1239</issn><eissn>1478-1239</eissn><abstract>Summary
Background
Antibodies to infliximab (ATI) can complicate infliximab (IFX) treatment of inflammatory bowel disease (IBD) patients.
Aims
To identify a clinically relevant threshold for ATI using a drug‐tolerant assay and to clarify factors for ATI development and their relation to clinical outcomes.
Methods
A cohort study of all IBD patients receiving IFX from May 2016 to April 2017 at a tertiary referral centre. Clinical data and serial therapeutic drug monitoring (at every infusion after the first) were collected.
Results
Over 12 months follow‐up, 113/214 (53%) patients had positive ATI, 94/214 (44%) had negative ATI and 7/214 (3%) had transient ATI. Concomitant immunosuppression was negatively associated with ATI positivity: thiopurines OR 0.48, methotrexate OR 0.36. ATI formation was more likely to be preceded by subtherapeutic IFX levels (57%) than vice versa (9%). Positive ATI were significantly associated with infusion reactions, loss of clinical remission and a reduction in IFX levels. In patients positive for ATI at first maintenance dose, 71% were treatment failures by second maintenance dose compared to 28% in those with negative ATI (P < .01). An ATI threshold of 2.5 mg/L had a sensitivity of 0.78 and a specificity of 0.63 in detecting loss of clinical remission ≤8 weeks.
Conclusions
There is a high prevalence of positive ATI and subtherapeutic IFX in IBD patients. Early ATI post induction is associated with a high rate of rapid treatment failure. ATI are significantly associated with loss of clinical remission. A lower ATI threshold of 2.5 mg/L has high sensitivity for loss of clinical remission.</abstract><doi>10.1002/ygh2.363</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1551-9174</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1478-1239 |
| ispartof | GastroHep, 2019-09, Vol.1 (5), p.214-222 |
| issn | 1478-1239 1478-1239 |
| language | eng |
| recordid | cdi_crossref_primary_10_1002_ygh2_363 |
| source | Access via Wiley Online Library |
| subjects | Crohn's disease inflammatory bowel disease infliximab ulcerative colitis |
| title | High prevalence of antibodies to infliximab and their relation to clinical outcomes in inflammatory bowel disease patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T11%3A47%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20prevalence%20of%20antibodies%20to%20infliximab%20and%20their%20relation%20to%20clinical%20outcomes%20in%20inflammatory%20bowel%20disease%20patients&rft.jtitle=GastroHep&rft.au=Tun,%20Gloria%20S.%20Z.&rft.date=2019-09&rft.volume=1&rft.issue=5&rft.spage=214&rft.epage=222&rft.pages=214-222&rft.issn=1478-1239&rft.eissn=1478-1239&rft_id=info:doi/10.1002/ygh2.363&rft_dat=%3Cwiley_cross%3EYGH2363%3C/wiley_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |