{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:13:38Z","timestamp":1789748018163,"version":"4.0.1"},"reference-count":33,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fresenius Kabi SwissBioSim GmbH"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,1,20]]},"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate the efficacy, immunogenicity and safety of the proposed biosimilar MSB11456 versus European Union (EU)-approved tocilizumab reference product in patients with rheumatoid arthritis (RA) in a multicentre, randomised, double-blind, multinational, parallel-group study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04512001\">NCT04512001<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult patients with moderate-to-severe active RA and inadequate clinical response to \u22651 disease-modifying antirheumatic drug (synthetic or biologic) receiving methotrexate were randomised to receive 24 weekly subcutaneous 162\u2009mg injections of either MSB11456 or EU-approved tocilizumab. Equivalence between treatments was considered if the 95% CI (European Medicines Agency)\/90%\u2009CI (US Food and Drug Administration) for the difference in mean change from baseline to week 24 in Disease Activity Score-28 Joint Count with erythrocyte sedimentation rate (DAS28-ESR) between treatments was entirely within prespecified equivalence intervals (\u22120.6 to 0.6 and \u22120.6 to 0.5, respectively). At week 24, patients were rerandomised to continued treatment or MSB11456. Secondary efficacy endpoints to week 52, and safety and immunogenicity to week 55 were also evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At week 24, the least squares mean difference in the change from baseline in DAS28-ESR between treatments was 0.01 (95% CI \u22120.19 to 0.22) in the 604 randomised patients. Similarity between treatments was shown for all other efficacy, safety and immunogenicity endpoints, including in patients who switched from EU-approved tocilizumab to MSB114466.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Therapeutic equivalence was demonstrated for efficacy endpoints, and safety and immunogenicity analyses support the similarity of the two treatments. The results of this study strengthen the evidence that the proposed biosimilar MSB11456 and EU-approved tocilizumab exert similar clinical effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2023-003596","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T12:25:45Z","timestamp":1707135945000},"page":"e003596","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04512001","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04512001","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Anna","family":"Zubrzycka-Sienkiewicz","sequence":"first","affiliation":[{"name":"'Reumatika - Centrum Reumatologil' NZOZ, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamilla","family":"Klama","sequence":"additional","affiliation":[{"name":"Solumed, Wielkopolskie, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ullmann","sequence":"additional","affiliation":[{"name":"Fresenius Kabi SwissBioSim GmbH, Eysins, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Petit-Frere","sequence":"additional","affiliation":[{"name":"Fresenius Kabi SwissBioSim GmbH, Eysins, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Baker","sequence":"additional","affiliation":[{"name":"Fresenius Kabi SwissBioSim GmbH, Eysins, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle","family":"Monnet","sequence":"additional","affiliation":[{"name":"Fresenius Kabi SwissBioSim GmbH, Eysins, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0346-8011","authenticated-orcid":false,"given":"Andras","family":"Illes","sequence":"additional","affiliation":[{"name":"Fresenius Kabi SwissBioSim GmbH, Eysins, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"2025090313012163000_10.1.e003596.1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S150580"},{"key":"2025090313012163000_10.1.e003596.2","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X10378372"},{"key":"2025090313012163000_10.1.e003596.3","unstructured":"Genentech, Inc . 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Scientific considerations in demonstrating biosimilarity to a reference product. guidance for industry. 2015a. Available: https:\/\/www.fda.gov\/media\/82647\/download [Accessed 31 Oct 2022]."},{"key":"2025090313012163000_10.1.e003596.9","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research . Quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. guidance for industry. 2015b. Available: https:\/\/www.fda.gov\/media\/135612\/download [Accessed 31 Oct 2022]."},{"key":"2025090313012163000_10.1.e003596.10","unstructured":"U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research . Quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. 2016. 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