{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:15:18Z","timestamp":1765779318713,"version":"3.48.0"},"reference-count":21,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,9,28]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This post hoc analysis compared the immunogenicity of the biosimilar adalimumab-adbm (Cyltezo) with the adalimumab reference product (RP; Humira) across indications, including rheumatoid arthritis (RA), Crohn\u2019s disease (CD) and plaque psoriasis (PsO), and by patient sex in the VOLTAIRE trials programme.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In each active-comparator randomised controlled trial (RCT), immunogenicity was assessed at various time points by the proportion of patients with antidrug antibodies (ADAs) and neutralising antibodies (nAbs), using acid dissociation followed by electrochemiluminescence assay. Assay sensitivity was 50\u2009ng\/mL, and drug tolerance was \u226530\u2009\u00b5g\/mL (free drug) at the low positive control level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Minor differences in immunogenicity parameters (ADAs, ADA titres and nAbs) were evident between adalimumab-adbm and adalimumab RP across these three immune-mediated inflammatory diseases (IMIDs). The proportion of ADA-positive and nAb-positive patients increased from baseline over time in all three RCTs, as expected, and was similar in the RA and CD RCTs but with higher numbers of ADA-positive and nAb-positive patients reported in the PsO trial. Subgroup analysis by patient sex showed the same trend.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Differences among the RCTs may partially be explained by concomitant background therapy (methotrexate) in the RA trial, stable doses of azathioprine, 6-mercaptopurine or methotrexate in 36% of patients with CD and absence of background therapy in the PsO RCT. The analyses further confirm the biosimilarity of adalimumab-adbm with the adalimumab RP across IMIDs and provide supporting evidence that adalimumab-adbm is an interchangeable biosimilar with consistent clinical results in patients originally treated with the RP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration numbers<\/jats:title>\n                    <jats:p>\n                      VOLTAIRE-RA (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02137226\">NCT02137226<\/jats:ext-link>\n                      ; EudraCT 2012-002945-40); VOLTAIRE-CD (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02871635\">NCT02871635<\/jats:ext-link>\n                      ; EudraCT 2016-000612-14); VOLTAIRE-PsO (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02850965\">NCT02850965<\/jats:ext-link>\n                      ; EudraCT 2016-000613-79).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-081687","type":"journal-article","created":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T21:55:20Z","timestamp":1731880520000},"page":"e081687","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Immunogenicity of adalimumab reference product and adalimumab-adbm in patients with rheumatoid arthritis, Crohn\u2019s disease and chronic plaque psoriasis: a pooled analysis of the VOLTAIRE trials"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct02137226","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02871635","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02850965","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02137226","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02871635","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02850965","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02640612","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-4072","authenticated-orcid":false,"given":"Vibeke","family":"Strand","sequence":"first","affiliation":[{"name":"Division of Immunology\/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy","family":"McCabe","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun","family":"Bender","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA"},{"name":"Alnylam Pharmaceuticals Inc, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"2025121422114694000_14.11.e081687.1","unstructured":"CYLTEZO (adalimumab-adbm) injection for subcutaneous use I. Full prescribing information. Boehringer Ingelheim International GmbH, Ridgefield, CT, USA, 2017. Available: https:\/\/docs.boehringer-ingelheim.com\/Prescribing%20Information\/PIs\/Cyltezo\/Cyltezo.pdf?DMW_FORMAT=pdf"},{"key":"2025121422114694000_14.11.e081687.2","unstructured":"US Food and Drug Administration . FDA news release. FDA approves Cyltezo, the first interchangeable biosimilar to Humira second interchangeable biosimilar product approved by agency, Available: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-cyltezo-firstinterchangeable-biosimilar-humira"},{"key":"2025121422114694000_14.11.e081687.3","unstructured":"HUMIRA\u00ae (adalimumab) injection for subcutaneous use. Full prescribing information. AbbVie Inc. Chicago, IL, USA, 2002. Available: https:\/\/www.rxabbvie.com\/pdf\/humira.pdf"},{"key":"2025121422114694000_14.11.e081687.4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s40744-020-00259-8","article-title":"Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity","volume":"8","author":"Huizinga","year":"2021","journal-title":"Rheumatol Ther"},{"key":"2025121422114694000_14.11.e081687.5","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1080\/13543784.2016.1255724","article-title":"Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE\u00ae-PK) in healthy subjects","volume":"25","author":"Wynne","year":"2016","journal-title":"Expert Opin Investig Drugs"},{"key":"2025121422114694000_14.11.e081687.6","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212245"},{"key":"2025121422114694000_14.11.e081687.7","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S2468-1253(21)00252-1","article-title":"Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn\u2019s disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial","volume":"6","author":"Hanauer","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2025121422114694000_14.11.e081687.8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/14712598.2021.1851362","article-title":"Similar efficacy, safety, and immunogenicity of the biosimilar BI 695501 and adalimumab reference product in patients with moderate-to-severe chronic plaque psoriasis: results from the randomized Phase III VOLTAIRE-PSO study","volume":"21","author":"Menter","year":"2021","journal-title":"Expert Opin Biol Ther"},{"key":"2025121422114694000_14.11.e081687.9","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01365","article-title":"Drug Tolerant Anti-drug Antibody Assay for Infliximab Treatment in Clinical Practice Identifies Positive Cases Earlier","volume":"11","author":"Kharlamova","year":"2020","journal-title":"Front Immunol"},{"key":"2025121422114694000_14.11.e081687.10","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202220"},{"key":"2025121422114694000_14.11.e081687.11","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2016.00021","article-title":"Immunogenicity to Biotherapeutics - The Role of Anti-drug Immune Complexes","volume":"7","author":"Krishna","year":"2016","journal-title":"Front Immunol"},{"key":"2025121422114694000_14.11.e081687.12","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1093\/rheumatology\/kex434","article-title":"Drug safety and immunogenicity of tumour necrosis factor inhibitors: the story so far","volume":"57","author":"Jani","year":"2018","journal-title":"Rheumatology (Oxford)"},{"key":"2025121422114694000_14.11.e081687.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(02)80075-3"},{"key":"2025121422114694000_14.11.e081687.14","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3974"},{"key":"2025121422114694000_14.11.e081687.15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/sji.12572","article-title":"Assays for Infliximab Drug Levels and Antibodies: A Matter of Scales and Categories","volume":"86","author":"Bader","year":"2017","journal-title":"Scand J Immunol"},{"key":"2025121422114694000_14.11.e081687.16","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3283521c4e"},{"key":"2025121422114694000_14.11.e081687.17","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.4"},{"key":"2025121422114694000_14.11.e081687.18","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.4155\/bio-2018-0091","article-title":"Sensitivity and Drug Tolerance of Antidrug Antibody Assays in Relation to Positive Control Characteristics","volume":"10","author":"Egging","year":"2018","journal-title":"Bioanalysis"},{"key":"2025121422114694000_14.11.e081687.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2012.03.016"},{"key":"2025121422114694000_14.11.e081687.20","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.801532","article-title":"Relationship Between Patient Sex and Serum Tumor Necrosis Factor Antagonist Drug and Anti-drug Antibody Concentrations in Inflammatory Bowel Disease; 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