HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy
IntroductionAnti-TNF treatment failure in patients with IBD is common. International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sou...
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| Veröffentlicht in: | Gut 2021-11, Vol.70 (Suppl 4), p.A31-A32 |
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| creator | Chanchlani, Neil Lin, Simeng Thomas, Amanda Hamilton, Ben Nice, Rachel Chee, Desmond Kennedy, Nick Goodhand, James Ahmad, Tariq |
| description | IntroductionAnti-TNF treatment failure in patients with IBD is common. International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sought to define the: 1) risk of immunogenicity to a second anti-TNF stratified by immunogenicity to first anti-TNF, 2) rates of drug persistence following failure to first anti-TNF drug and 3) strategies to mitigate development of immunogenicity.MethodsWe performed a retrospective cohort study across 38 UK hospitals. 1058 patients [532 (51%) male, 755 (71%) Crohn’s disease] had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to October 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug-tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgery, and patients were identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level |
| doi_str_mv | 10.1136/gutjnl-2021-BSG.56 |
| format | Article |
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International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sought to define the: 1) risk of immunogenicity to a second anti-TNF stratified by immunogenicity to first anti-TNF, 2) rates of drug persistence following failure to first anti-TNF drug and 3) strategies to mitigate development of immunogenicity.MethodsWe performed a retrospective cohort study across 38 UK hospitals. 1058 patients [532 (51%) male, 755 (71%) Crohn’s disease] had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to October 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug-tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgery, and patients were identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level <2 mg/L, adalimumab level <6 mg/L) with an antibody concentration ≥10 AU/ml. Pharmacodynamic (PD) failure was defined as treatment failure despite adequate drug levels.ResultsPatients who developed immunogenicity to adalimumab (first) were more likely to develop immunogenicity to infliximab (second) (64% vs 40%, p < 0.001), and patients who developed immunogenicity to infliximab (first) were more likely to develop immunogenicity to adalimumab (second) (34% vs 20%, p = 0.002). Patients who developed: antibodies and undetectable drug, low drug levels, or low drug levels with immunogenicity to infliximab (first), were more likely to develop these outcomes to adalimumab (second) (all p<0.001).There was no difference in drug persistence to second anti-TNF in patients with pharmacodynamic and immunogenic treatment failure to first anti-TNF (p = 0.86). In patients with immunogenic (but not pharmacodynamic) failure, commencing an immunomodulator at the time of switching to second anti-TNF drug was associated with longer drug persistence than in patients treated with an immunomodulator throughout or not all (Figure 1).Abastract HMO-4 Figure 1Drug persistence to second anti-TNF in patients stratified by immunomodulator useConclusionsImmunogenicity to the first anti-TNF was associated with immunogenicity to the second anti-TNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to second anti-TNF was associated with improved drug persistence in immunogenic, but not pharmacodynamic, failure. However, 50% of patients remained on second anti-TNF at 5 years in both groups, suggesting switching in-class may be appropriate, irrespective of the cause of treatment failure to first anti-TNF.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2021-BSG.56</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher><subject>Antibodies ; Crohn's disease ; Enzyme-linked immunosorbent assay ; GLP-1 receptor agonists ; Immunogenicity ; Immunomodulation ; Infliximab ; Monoclonal antibodies ; Patients ; Pharmacodynamics ; Posters – highly commended ; Therapeutic drug monitoring ; Tumor necrosis factor-α</subject><ispartof>Gut, 2021-11, Vol.70 (Suppl 4), p.A31-A32</ispartof><rights>Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Chanchlani, Neil</creatorcontrib><creatorcontrib>Lin, Simeng</creatorcontrib><creatorcontrib>Thomas, Amanda</creatorcontrib><creatorcontrib>Hamilton, Ben</creatorcontrib><creatorcontrib>Nice, Rachel</creatorcontrib><creatorcontrib>Chee, Desmond</creatorcontrib><creatorcontrib>Kennedy, Nick</creatorcontrib><creatorcontrib>Goodhand, James</creatorcontrib><creatorcontrib>Ahmad, Tariq</creatorcontrib><title>HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy</title><title>Gut</title><addtitle>Gut</addtitle><description>IntroductionAnti-TNF treatment failure in patients with IBD is common. International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sought to define the: 1) risk of immunogenicity to a second anti-TNF stratified by immunogenicity to first anti-TNF, 2) rates of drug persistence following failure to first anti-TNF drug and 3) strategies to mitigate development of immunogenicity.MethodsWe performed a retrospective cohort study across 38 UK hospitals. 1058 patients [532 (51%) male, 755 (71%) Crohn’s disease] had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to October 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug-tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgery, and patients were identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level <2 mg/L, adalimumab level <6 mg/L) with an antibody concentration ≥10 AU/ml. Pharmacodynamic (PD) failure was defined as treatment failure despite adequate drug levels.ResultsPatients who developed immunogenicity to adalimumab (first) were more likely to develop immunogenicity to infliximab (second) (64% vs 40%, p < 0.001), and patients who developed immunogenicity to infliximab (first) were more likely to develop immunogenicity to adalimumab (second) (34% vs 20%, p = 0.002). Patients who developed: antibodies and undetectable drug, low drug levels, or low drug levels with immunogenicity to infliximab (first), were more likely to develop these outcomes to adalimumab (second) (all p<0.001).There was no difference in drug persistence to second anti-TNF in patients with pharmacodynamic and immunogenic treatment failure to first anti-TNF (p = 0.86). In patients with immunogenic (but not pharmacodynamic) failure, commencing an immunomodulator at the time of switching to second anti-TNF drug was associated with longer drug persistence than in patients treated with an immunomodulator throughout or not all (Figure 1).Abastract HMO-4 Figure 1Drug persistence to second anti-TNF in patients stratified by immunomodulator useConclusionsImmunogenicity to the first anti-TNF was associated with immunogenicity to the second anti-TNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to second anti-TNF was associated with improved drug persistence in immunogenic, but not pharmacodynamic, failure. However, 50% of patients remained on second anti-TNF at 5 years in both groups, suggesting switching in-class may be appropriate, irrespective of the cause of treatment failure to first anti-TNF.</description><subject>Antibodies</subject><subject>Crohn's disease</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>GLP-1 receptor agonists</subject><subject>Immunogenicity</subject><subject>Immunomodulation</subject><subject>Infliximab</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Pharmacodynamics</subject><subject>Posters – highly commended</subject><subject>Therapeutic drug monitoring</subject><subject>Tumor necrosis factor-α</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpFkLtOwzAYhS0EEqXwAkyWWGBw8T02W6noRWrp0OxR4jrBUWKXXIZuLLwoT0JQQUz_8p3zH30A3BI8IYTJx6LvSl8hiilBz7vFRMgzMCJcKsSoUudghDGJkIi4vgRXbVtijJXSZATK5WaL-NfH56quex8K651x3RF2AbbWBL-Hqe8cil_nsHuzTXo4wvvVZjeNH56gqw-VM2nngm9hHpoh8d5bb5wvYMhh5kIVCmf-gtfgIk-r1t783jGI5y_xbInW28VqNl2jjBAikRRZbmTEMp5To_faCq41T7Wyw2aLJeacaYEjnMtcUSIyqwjfS2MZYZZqNgZ3p9pDE4Y5bZeUoW_88DGhQnMtoojSgZqcqKwu_wGCkx-dyUln8qMzGXQmQrJv-7BqDg</recordid><startdate>20211107</startdate><enddate>20211107</enddate><creator>Chanchlani, Neil</creator><creator>Lin, Simeng</creator><creator>Thomas, Amanda</creator><creator>Hamilton, Ben</creator><creator>Nice, Rachel</creator><creator>Chee, Desmond</creator><creator>Kennedy, Nick</creator><creator>Goodhand, James</creator><creator>Ahmad, Tariq</creator><general>BMJ Publishing Group Ltd and British Society of Gastroenterology</general><general>BMJ Publishing Group LTD</general><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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>20211107</creationdate><title>HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy</title><author>Chanchlani, Neil ; Lin, Simeng ; Thomas, Amanda ; Hamilton, Ben ; Nice, Rachel ; Chee, Desmond ; Kennedy, Nick ; Goodhand, James ; Ahmad, Tariq</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1116-65bfc673b4f2c9d9e54994a98e008e06044395070f6f8215be814d6ce313e293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Crohn's disease</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>GLP-1 receptor agonists</topic><topic>Immunogenicity</topic><topic>Immunomodulation</topic><topic>Infliximab</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Pharmacodynamics</topic><topic>Posters – highly commended</topic><topic>Therapeutic drug monitoring</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chanchlani, Neil</creatorcontrib><creatorcontrib>Lin, Simeng</creatorcontrib><creatorcontrib>Thomas, Amanda</creatorcontrib><creatorcontrib>Hamilton, Ben</creatorcontrib><creatorcontrib>Nice, Rachel</creatorcontrib><creatorcontrib>Chee, Desmond</creatorcontrib><creatorcontrib>Kennedy, Nick</creatorcontrib><creatorcontrib>Goodhand, James</creatorcontrib><creatorcontrib>Ahmad, Tariq</creatorcontrib><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>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><jtitle>Gut</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chanchlani, Neil</au><au>Lin, Simeng</au><au>Thomas, Amanda</au><au>Hamilton, Ben</au><au>Nice, Rachel</au><au>Chee, Desmond</au><au>Kennedy, Nick</au><au>Goodhand, James</au><au>Ahmad, Tariq</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy</atitle><jtitle>Gut</jtitle><stitle>Gut</stitle><date>2021-11-07</date><risdate>2021</risdate><volume>70</volume><issue>Suppl 4</issue><spage>A31</spage><epage>A32</epage><pages>A31-A32</pages><issn>0017-5749</issn><eissn>1468-3288</eissn><abstract>IntroductionAnti-TNF treatment failure in patients with IBD is common. International guidelines recommend switching out of class when anti-TNF drug levels are therapeutic and within class with an immunomodulator when anti-TNF drug levels are suboptimal and associated with antibody development.We sought to define the: 1) risk of immunogenicity to a second anti-TNF stratified by immunogenicity to first anti-TNF, 2) rates of drug persistence following failure to first anti-TNF drug and 3) strategies to mitigate development of immunogenicity.MethodsWe performed a retrospective cohort study across 38 UK hospitals. 1058 patients [532 (51%) male, 755 (71%) Crohn’s disease] had both infliximab and adalimumab therapeutic drug monitoring performed by our service from May 2013 to October 2020 were identified. Drug and antibody levels were measured using the IDKmonitor® drug-tolerant ELISA assays. Treatment failure included primary nonresponse, secondary loss of response, adverse drug reactions and IBD-related surgery, and patients were identified by case note review. Immunogenic failure was defined as treatment failure with suboptimal drug levels (infliximab level <2 mg/L, adalimumab level <6 mg/L) with an antibody concentration ≥10 AU/ml. Pharmacodynamic (PD) failure was defined as treatment failure despite adequate drug levels.ResultsPatients who developed immunogenicity to adalimumab (first) were more likely to develop immunogenicity to infliximab (second) (64% vs 40%, p < 0.001), and patients who developed immunogenicity to infliximab (first) were more likely to develop immunogenicity to adalimumab (second) (34% vs 20%, p = 0.002). Patients who developed: antibodies and undetectable drug, low drug levels, or low drug levels with immunogenicity to infliximab (first), were more likely to develop these outcomes to adalimumab (second) (all p<0.001).There was no difference in drug persistence to second anti-TNF in patients with pharmacodynamic and immunogenic treatment failure to first anti-TNF (p = 0.86). In patients with immunogenic (but not pharmacodynamic) failure, commencing an immunomodulator at the time of switching to second anti-TNF drug was associated with longer drug persistence than in patients treated with an immunomodulator throughout or not all (Figure 1).Abastract HMO-4 Figure 1Drug persistence to second anti-TNF in patients stratified by immunomodulator useConclusionsImmunogenicity to the first anti-TNF was associated with immunogenicity to the second anti-TNF, irrespective of drug sequence. Commencing an immunomodulator at the time of switching to second anti-TNF was associated with improved drug persistence in immunogenic, but not pharmacodynamic, failure. However, 50% of patients remained on second anti-TNF at 5 years in both groups, suggesting switching in-class may be appropriate, irrespective of the cause of treatment failure to first anti-TNF.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Society of Gastroenterology</pub><doi>10.1136/gutjnl-2021-BSG.56</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies Crohn's disease Enzyme-linked immunosorbent assay GLP-1 receptor agonists Immunogenicity Immunomodulation Infliximab Monoclonal antibodies Patients Pharmacodynamics Posters – highly commended Therapeutic drug monitoring Tumor necrosis factor-α |
| title | HMO-4 Immunogenicity to second anti-TNF therapy (IMSAT): implications for sequencing of biologic therapy |
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