{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:53:16Z","timestamp":1793083996406,"version":"4.5.0"},"reference-count":34,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"unspecified","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/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":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,12,11]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the impact of rheumatoid factor (RF) levels and previous inadequate responses\/intolerance to tumour necrosis factor inhibitors (TNFi-IR) on the efficacy of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) through a post hoc analysis of the RA Evaluation in Subjects Receiving TNF Inhibitor CZP (REALISTIC) trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the phase IIIb REALISTIC trial, patients with RA were randomised to CZP (400\u2009mg at weeks 0, 2 and 4, then 200\u2009mg every 2\u2009weeks) or placebo (PBO) for 12 weeks, followed by open-label CZP (minimum 16 weeks). Outcomes reported to week 36 include Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI) scores, rates of DAS28-CRP &lt;2.6\u2009and CDAI remission (CDAI \u22642.8) and components of each. Data were stratified by baseline RF level (\u22643rd quarter (\u2264Q3; &lt;180 kU\/L) vs 4th quarter (Q4; \u2018high RF\u2019; \u2265180 kU\/L)) and prior TNFi use (TNFina\u00efve vs TNFi-IR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 930 patients were included: 751 CZP-randomised and 179 PBO-randomised. At week 12, CZP-randomised patients experienced marked and similar improvements in disease activity, irrespective of RF level and prior TNFi use, while PBO-randomised patients did not. Responses generally improved through week 36 in CZP-treated patients (including PBO-randomised switchers), with similar efficacy across subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with high and low RF levels experienced similar clinical responses to CZP treatment, irrespective of previous inadequate responses or intolerance to TNFis. These findings expand previous observations, supporting CZP as an effective treatment for patients with RA who have high RF levels and prior inadequate responses to TNFis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT00717236\">NCT00717236<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-006094","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:25:20Z","timestamp":1769772320000},"page":"e006094","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Do high rheumatoid factor levels impact response to certolizumab pegol in patients with inadequately controlled rheumatoid arthritis? A post hoc analysis of the phase IIIb REALISTIC trial"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct00717236","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00717236","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-8877","authenticated-orcid":false,"given":"Josef S","family":"Smolen","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted R","family":"Mikuls","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-2781","authenticated-orcid":false,"given":"James","family":"Galloway","sequence":"additional","affiliation":[{"name":"Centre for Rheumatic Diseases, King\u2019s College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"M\u00fcller-Ladner","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R","family":"Curtis","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University, Tokyo, Japan"},{"name":"Department of Rheumatology and Allied Immunology, Saitama Medical University, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4459-8609","authenticated-orcid":false,"given":"Ernest","family":"Choy","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Molecular Targeted Therapeutics, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan"},{"name":"First Department of Internal Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cara","sequence":"additional","affiliation":[{"name":"UCB, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-6151","authenticated-orcid":false,"given":"Bernard","family":"Lauwerys","sequence":"additional","affiliation":[{"name":"UCB, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Tilt","sequence":"additional","affiliation":[{"name":"UCB, Slough, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baran","family":"Ufuktepe","sequence":"additional","affiliation":[{"name":"UCB, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7766-6167","authenticated-orcid":false,"given":"Peter C","family":"Taylor","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"2026013003251137000_12.1.e006094.1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12829"},{"key":"2026013003251137000_12.1.e006094.2","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/art.38307","article-title":"Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis","volume":"66","author":"Sokolove","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"2026013003251137000_12.1.e006094.3","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0597-374"},{"key":"2026013003251137000_12.1.e006094.4","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-017-1266-4","article-title":"Poor prognostic factors guiding treatment decisions in rheumatoid arthritis patients: a review of data from randomized clinical trials and cohort studies","volume":"19","author":"Albrecht","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"2026013003251137000_12.1.e006094.5","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1007\/s10067-014-2756-2","article-title":"Clinical parameters and biomarkers for anti-TNF treatment prognosis in rheumatoid arthritis patients","volume":"33","author":"Cuchacovich","year":"2014","journal-title":"Clin Rheumatol"},{"key":"2026013003251137000_12.1.e006094.6","doi-asserted-by":"crossref","DOI":"10.1177\/11795441211028751","article-title":"Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies","volume":"14","author":"Fazeli","year":"2021","journal-title":"Clin Med Insights Arthritis Musculoskelet Disord"},{"key":"2026013003251137000_12.1.e006094.7","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1093\/rheumatology\/keac586","article-title":"Development of a scoring model for the Sharp\/van der Heijde score using convolutional neural networks and its clinical application","volume":"62","author":"Honda","year":"2023","journal-title":"Rheumatology (Oxford)"},{"key":"2026013003251137000_12.1.e006094.8","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.090188"},{"key":"2026013003251137000_12.1.e006094.9","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.ejr.2022.04.004","article-title":"Disease characteristics in high versus low titers of rheumatoid factor or anti-citrullinated peptide antibody in rheumatoid arthritis patients","volume":"44","author":"Sobhy","year":"2022","journal-title":"The Egyptian Rheumatologist"},{"key":"2026013003251137000_12.1.e006094.10","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s13075-017-1401-2","article-title":"High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study","volume":"19","author":"Takeuchi","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"2026013003251137000_12.1.e006094.11","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep155"},{"key":"2026013003251137000_12.1.e006094.12","doi-asserted-by":"crossref","first-page":"ii15","DOI":"10.1093\/rheumatology\/keaf035","article-title":"Rheumatoid factors revisited in the age of biologic therapy","volume":"64","author":"Avci","year":"2025","journal-title":"Rheumatology (Oxford)"},{"key":"2026013003251137000_12.1.e006094.13","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-015-0736-9","article-title":"Rheumatoid factor, not antibodies against citrullinated proteins, is associated with baseline disease activity in rheumatoid arthritis clinical trials","volume":"17","author":"Aletaha","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2026013003251137000_12.1.e006094.14","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/annrheumdis-2024-eular.2568","article-title":"POS0722\u2005PURIFIED MONOCLONAL RHEUMATOID FACTORS BIND FC CONTAINING TNF INHIBITORS IN VITRO BUT NOT THE FC-FREE TNF INHIBITOR, CERTOLIZUMAB PEGOL","volume":"83","author":"Bidgood","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"2026013003251137000_12.1.e006094.15","unstructured":"Kanda-Satoh YM , Sonomoto K , Ufuktepe B , et al . Does rheumatoid factor level affect the pharmacodynamics of disease-modifying antirheumatic drugs and the efficacy of tumour necrosis factor inhibitors with different molecular structures? in vitro and clinical findings from the FIRST registry. Presented at JCR 2024, 33; 2024"},{"key":"2026013003251137000_12.1.e006094.16","doi-asserted-by":"crossref","first-page":"ii9","DOI":"10.1093\/rheumatology\/keaf003","article-title":"What is rheumatoid factor? From screening to personalized management","volume":"64","author":"Tanaka","year":"2025","journal-title":"Rheumatology (Oxford)"},{"key":"2026013003251137000_12.1.e006094.17","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1136\/annrheumdis-2022-eular.2486","article-title":"POS0647\u2005DOES TNF INHIBITOR MOLECULAR STRUCTURE MATTER? ANALYSIS OF IMPACT OF BASELINE RHEUMATOID FACTOR TITERS ON DRUG LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS","volume":"81","author":"Mart\u00ednez-Feito","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"2026013003251137000_12.1.e006094.18","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s00296-021-05086-w","article-title":"Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study","volume":"42","author":"Nakayama","year":"2022","journal-title":"Rheumatol Int"},{"key":"2026013003251137000_12.1.e006094.19","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq285"},{"key":"2026013003251137000_12.1.e006094.20","doi-asserted-by":"crossref","unstructured":"Takahiro Yamano KY , Iwao H , Sakai T , et al . W43-5: Usefulness of certolizumab pegol useful rheumatoid arthritis with high rheumatoid factor. Mod Rheumatol 2024;34. doi:10.1371\/journal.pone.0126582","DOI":"10.1371\/journal.pone.0126582"},{"key":"2026013003251137000_12.1.e006094.21","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/1756-185X.14699","article-title":"Efficacy of certolizumab pegol across baseline rheumatoid factor subgroups in patients with rheumatoid arthritis: Post-hoc analysis of clinical trials","volume":"26","author":"Tanaka","year":"2023","journal-title":"Int J Rheum Dis"},{"key":"2026013003251137000_12.1.e006094.22","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1093\/rheumatology\/keae435","article-title":"Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis","volume":"63","author":"Smolen","year":"2024","journal-title":"Rheumatology (Oxford)"},{"key":"2026013003251137000_12.1.e006094.23","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes150"},{"key":"2026013003251137000_12.1.e006094.24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1186\/s13075-015-0841-9","article-title":"Twenty-eight-week results from the REALISTIC phase IIIb randomized trial: efficacy, safety and predictability of response to certolizumab pegol in a diverse rheumatoid arthritis population","volume":"17","author":"Weinblatt","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"2026013003251137000_12.1.e006094.25","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"2026013003251137000_12.1.e006094.26","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223413"},{"key":"2026013003251137000_12.1.e006094.27","unstructured":"FDA . US humira prescribng information. Volume 2024. 2014. Available: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/125057s356lbl.pdf"},{"key":"2026013003251137000_12.1.e006094.28","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002817","article-title":"Rheumatoid factor isotypes in rheumatoid arthritis diagnosis and prognosis: a systematic review and meta-analysis","volume":"9","author":"Motta","year":"2023","journal-title":"RMD Open"},{"key":"2026013003251137000_12.1.e006094.29","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-020-2122-5","article-title":"Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study","volume":"22","author":"Ochi","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"2026013003251137000_12.1.e006094.30","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.00589","article-title":"What Is the Clinical Relevance of TNF Inhibitor Immunogenicity in the Management of Patients With Rheumatoid Arthritis?","volume":"11","author":"Mehta","year":"2020","journal-title":"Front Immunol"},{"key":"2026013003251137000_12.1.e006094.31","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1002\/acr.24596","article-title":"2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2026013003251137000_12.1.e006094.32","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216655"},{"key":"2026013003251137000_12.1.e006094.33","doi-asserted-by":"crossref","DOI":"10.1177\/1759720X221114101","article-title":"Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes","volume":"14","author":"Taylor","year":"2022","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"2026013003251137000_12.1.e006094.34","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203993"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2025-006094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:25:24Z","timestamp":1769772324000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2025-006094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,30]]},"published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1136\/rmdopen-2025-006094"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2025-006094","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]}}}