{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:21:34Z","timestamp":1783480894583,"version":"3.55.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    The study aimed to explore the bioequivalence of a proposed biosimilar BAT1806 to its reference products marketed in the EU and US (RoActemra-EU and Actemra-US) among healthy Chinese men. The tolerance, immunogenicity, and pharmacokinetics (PK) of the three drugs were also investigated.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    In this randomized, double-blind, single-dose, three-arm, parallel study, a single-dose of 4\u00a0mg\/kg of the reference products, or the biosimilar was administered to the participants. The participants were followed up for 57 days, and PK, immunogenicity, and tolerance evaluations were completed during this period.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The PK parameters were similar in all three groups: BAT1806 (\n                    <jats:italic>n<\/jats:italic>\n                    = 45), RoActemra-EU (\n                    <jats:italic>n<\/jats:italic>\n                    = 42), and Actemra-US (\n                    <jats:italic>n<\/jats:italic>\n                    = 42). The 90% confidence intervals (CIs) for the ratios of C\n                    <jats:sub>\n                      <jats:italic>max<\/jats:italic>\n                    <\/jats:sub>\n                    , AUC\n                    <jats:sub>\n                      0\u2013\n                      <jats:italic>t<\/jats:italic>\n                    <\/jats:sub>\n                    and AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    were 86.90\u2013104.41% for BAT1806 vs. RoActemra-EU, 91.70\u2013106.15% for BAT1806 vs Actemra-US, and 90.04\u2013105.53% for Actemra-US vs RoActemra-EU. For all comparisons, the 90% CIs for the C\n                    <jats:sub>\n                      <jats:italic>max<\/jats:italic>\n                    <\/jats:sub>\n                    , AUC\n                    <jats:sub>\n                      0\u2013\n                      <jats:italic>t<\/jats:italic>\n                    <\/jats:sub>\n                    , and AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    were within the predefined bioequivalence limit of 80.00\u2013125.00%. The intersubject variability ranged from 14.5% to 21.5%, which was considerably low. Among the participants, 19 (42.2%), 10 (23.8%), and 12 (28.6%) from the BAT1806, RoActemra-EU, and Actemra-US groups were, respectively, found to be positive for anti-drug antibodies, while 14 (31.1%), nine (21.4%), and 12 (28.6%) were positive for neutralizing antibodies. Nevertheless, these antibodies did not affect the drug concentrations, and the outcomes in the bioequivalence tests were similar after sensitivity analysis. Treatment-related and treatment-emergent adverse events (TEAEs) were recorded in 27, 34, and 32 participants in the BAT1806, RoActemra-EU, and Actemra-US groups, respectively. The most common treatment-related adverse events observed were a decrease in neutrophil, and white blood cell counts.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The PK characteristics of BAT1806 were similar to those of the reference products, RoActemra-EU and Actemra-US. Both BAT1806 and the reference products exhibited low intersubject variability and similar safety profiles.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical trial registration number:<\/jats:bold>\n                    <jats:ext-link>http:\/\/www.chinadrugtrials.org.cn\/index.html<\/jats:ext-link>\n                    , CTR20180039;\n                    <jats:ext-link>https:\/\/clinicaltrials.gov\/NCT03606876<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.3389\/fphar.2020.609522","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T05:34:39Z","timestamp":1611552879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["A Phase I Clinical Study Comparing the Tolerance, Immunogenicity, and Pharmacokinetics of Proposed Biosimilar BAT1806 and Reference Tocilizumab in Healthy Chinese Men"],"prefix":"10.3389","volume":"11","author":[{"given":"Hong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinbo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/jcph.826","article-title":"Pharmacokinetic and pharmacodynamic analysis of subcutaneous tocilizumab in patients with rheumatoid arthritis from 2 randomized, controlled trials: SUMMACTA and BREVACTA","volume":"57","author":"Abdallah","year":"2017","journal-title":"J. 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