Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs
Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF...
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Veröffentlicht in: | International journal of molecular sciences 2023-05, Vol.24 (10), p.8695 |
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creator | Medina-Medina, Rosario Iglesias-Flores, Eva Benítez, Jose M Marín-Pedrosa, Sandra Salgueiro-Rodríguez, Isabel Linares, Clara I González-Rubio, Sandra Soto-Escribano, Pilar Gros, Beatriz Rodríguez-Perálvarez, Manuel L Cabriada, José L Chaparro, María Gisbert, Javier P Chicano-Gálvez, Eduardo Ortea, Ignacio Ferrín, Gustavo García-Sánchez, Valle Aguilar-Melero, Patricia |
description | Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (
≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (
< 0.001), whose differential expression was confirmed by ELISA (
= 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR. |
doi_str_mv | 10.3390/ijms24108695 |
format | Article |
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≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (
< 0.001), whose differential expression was confirmed by ELISA (
= 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24108695</identifier><identifier>PMID: 37240037</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adalimumab ; Antineoplastic Agents - therapeutic use ; Biological products ; Biomarkers ; Carbohydrate metabolism ; Carbohydrates ; Clinical medicine ; Comparative analysis ; Corticosteroids ; Crohn Disease - drug therapy ; Crohn's disease ; Cytokines ; Cytoskeleton ; Deregulation ; Drugs ; Gender ; Hemostasis ; Hemostatics ; Humans ; Immune response ; Immunosuppressive agents ; Immunotherapy ; Inflammatory bowel disease ; Infliximab - therapeutic use ; Microbiota ; Multivariate analysis ; Patients ; Physiological aspects ; Plasma ; Prediction models ; Prescription drugs ; Proteins ; Proteomics ; Quality of life ; Remission ; Remission (Medicine) ; Remission Induction ; Steroids ; Tumor necrosis factor ; Tumor Necrosis Factor Inhibitors - therapeutic use ; Tumor Necrosis Factor-alpha - therapeutic use ; Tumor necrosis factor-TNF ; Vinculin</subject><ispartof>International journal of molecular sciences, 2023-05, Vol.24 (10), p.8695</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c437t-ebb0a4bf05e85407fdb9fcf61475907b8e19d1251728ddbe14d1ff5b7a8094f43</cites><orcidid>0000-0002-5628-313X ; 0000-0003-1396-5445 ; 0000-0002-9481-9628 ; 0000-0001-8898-3141 ; 0000-0002-1795-2919 ; 0000-0002-3068-5659 ; 0000-0002-9275-4242 ; 0000-0003-2090-3445</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217828/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217828/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37240037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Medina-Medina, Rosario</creatorcontrib><creatorcontrib>Iglesias-Flores, Eva</creatorcontrib><creatorcontrib>Benítez, Jose M</creatorcontrib><creatorcontrib>Marín-Pedrosa, Sandra</creatorcontrib><creatorcontrib>Salgueiro-Rodríguez, Isabel</creatorcontrib><creatorcontrib>Linares, Clara I</creatorcontrib><creatorcontrib>González-Rubio, Sandra</creatorcontrib><creatorcontrib>Soto-Escribano, Pilar</creatorcontrib><creatorcontrib>Gros, Beatriz</creatorcontrib><creatorcontrib>Rodríguez-Perálvarez, Manuel L</creatorcontrib><creatorcontrib>Cabriada, José L</creatorcontrib><creatorcontrib>Chaparro, María</creatorcontrib><creatorcontrib>Gisbert, Javier P</creatorcontrib><creatorcontrib>Chicano-Gálvez, Eduardo</creatorcontrib><creatorcontrib>Ortea, Ignacio</creatorcontrib><creatorcontrib>Ferrín, Gustavo</creatorcontrib><creatorcontrib>García-Sánchez, Valle</creatorcontrib><creatorcontrib>Aguilar-Melero, Patricia</creatorcontrib><title>Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (
≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (
< 0.001), whose differential expression was confirmed by ELISA (
= 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.</description><subject>Adalimumab</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological products</subject><subject>Biomarkers</subject><subject>Carbohydrate metabolism</subject><subject>Carbohydrates</subject><subject>Clinical medicine</subject><subject>Comparative analysis</subject><subject>Corticosteroids</subject><subject>Crohn Disease - drug therapy</subject><subject>Crohn's disease</subject><subject>Cytokines</subject><subject>Cytoskeleton</subject><subject>Deregulation</subject><subject>Drugs</subject><subject>Gender</subject><subject>Hemostasis</subject><subject>Hemostatics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunosuppressive agents</subject><subject>Immunotherapy</subject><subject>Inflammatory bowel disease</subject><subject>Infliximab - therapeutic use</subject><subject>Microbiota</subject><subject>Multivariate analysis</subject><subject>Patients</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Prediction models</subject><subject>Prescription drugs</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Quality of life</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Remission Induction</subject><subject>Steroids</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor Inhibitors - 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therapeutic use</topic><topic>Biological products</topic><topic>Biomarkers</topic><topic>Carbohydrate metabolism</topic><topic>Carbohydrates</topic><topic>Clinical medicine</topic><topic>Comparative analysis</topic><topic>Corticosteroids</topic><topic>Crohn Disease - drug therapy</topic><topic>Crohn's disease</topic><topic>Cytokines</topic><topic>Cytoskeleton</topic><topic>Deregulation</topic><topic>Drugs</topic><topic>Gender</topic><topic>Hemostasis</topic><topic>Hemostatics</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunosuppressive agents</topic><topic>Immunotherapy</topic><topic>Inflammatory bowel disease</topic><topic>Infliximab - therapeutic use</topic><topic>Microbiota</topic><topic>Multivariate analysis</topic><topic>Patients</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Prediction models</topic><topic>Prescription drugs</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Quality of life</topic><topic>Remission</topic><topic>Remission (Medicine)</topic><topic>Remission Induction</topic><topic>Steroids</topic><topic>Tumor necrosis factor</topic><topic>Tumor Necrosis Factor Inhibitors - 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However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (
≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (
< 0.001), whose differential expression was confirmed by ELISA (
= 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37240037</pmid><doi>10.3390/ijms24108695</doi><orcidid>https://orcid.org/0000-0002-5628-313X</orcidid><orcidid>https://orcid.org/0000-0003-1396-5445</orcidid><orcidid>https://orcid.org/0000-0002-9481-9628</orcidid><orcidid>https://orcid.org/0000-0001-8898-3141</orcidid><orcidid>https://orcid.org/0000-0002-1795-2919</orcidid><orcidid>https://orcid.org/0000-0002-3068-5659</orcidid><orcidid>https://orcid.org/0000-0002-9275-4242</orcidid><orcidid>https://orcid.org/0000-0003-2090-3445</orcidid><oa>free_for_read</oa></addata></record> |
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source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | Adalimumab Antineoplastic Agents - therapeutic use Biological products Biomarkers Carbohydrate metabolism Carbohydrates Clinical medicine Comparative analysis Corticosteroids Crohn Disease - drug therapy Crohn's disease Cytokines Cytoskeleton Deregulation Drugs Gender Hemostasis Hemostatics Humans Immune response Immunosuppressive agents Immunotherapy Inflammatory bowel disease Infliximab - therapeutic use Microbiota Multivariate analysis Patients Physiological aspects Plasma Prediction models Prescription drugs Proteins Proteomics Quality of life Remission Remission (Medicine) Remission Induction Steroids Tumor necrosis factor Tumor Necrosis Factor Inhibitors - therapeutic use Tumor Necrosis Factor-alpha - therapeutic use Tumor necrosis factor-TNF Vinculin |
title | Development of a Prediction Model for Short-Term Remission of Patients with Crohn's Disease Treated with Anti-TNF Drugs |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T16%3A59%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20of%20a%20Prediction%20Model%20for%20Short-Term%20Remission%20of%20Patients%20with%20Crohn's%20Disease%20Treated%20with%20Anti-TNF%20Drugs&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Medina-Medina,%20Rosario&rft.date=2023-05-12&rft.volume=24&rft.issue=10&rft.spage=8695&rft.pages=8695-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms24108695&rft_dat=%3Cgale_pubme%3EA752423356%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2819453440&rft_id=info:pmid/37240037&rft_galeid=A752423356&rfr_iscdi=true |