{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T10:15:53Z","timestamp":1750846553509,"version":"3.37.3"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011110","name":"UCB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Certolizumab pegol (CZP) is a PEGylated Fc-free tumor necrosis factor (TNF) inhibitor antibody approved for use in the treatment of rheumatoid arthritis (RA), Crohn\u2019s disease, psoriatic arthritis, axial spondyloarthritis and psoriasis. In a clinical trial of patients with severe RA, CZP improved disease symptoms in approximately half of patients. However, variability in CZP efficacy remains a problem for clinicians, thus, the aim of this study was to identify genetic variants predictive of CZP response. We performed a genome-wide association study (GWAS) of 302 RA patients treated with CZP in the REALISTIC trial to identify common single nucleotide polymorphisms (SNPs) associated with treatment response. Whole-exome sequencing was also performed for 74 CZP extreme responders and non-responders within the same population, as well as 1546 population controls. No common SNPs or rare functional variants were significantly associated with CZP response, though a non-significant enrichment in the RA-implicated <jats:italic>KCNK5<\/jats:italic> gene was observed. Two SNPs near spondin-1 and semaphorin-4G approached genome-wide significance. The results of the current study did not provide an unambiguous predictor of CZP response.<\/jats:p>","DOI":"10.1371\/journal.pone.0261165","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:25:02Z","timestamp":1649784302000},"page":"e0261165","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population"],"prefix":"10.1371","volume":"17","author":[{"given":"Ian R.","family":"White","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9714-5155","authenticated-orcid":true,"given":"Sarah E.","family":"Kleinstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Praet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Chamberlain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"McHale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Maia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingxing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Urban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-5131","authenticated-orcid":true,"given":"Patrick R.","family":"Shea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"issue":"9","key":"pone.0261165.ref001","first-page":"646","article-title":"Burden of major musculoskeletal conditions","volume":"81","author":"AD Woolf","year":"2003","journal-title":"Bull World Health Organ"},{"issue":"5","key":"pone.0261165.ref002","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/acr.21641","article-title":"2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis","volume":"64","author":"JA Singh","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"issue":"9194","key":"pone.0261165.ref003","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/S0140-6736(99)05246-0","article-title":"Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. 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