{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:16:54Z","timestamp":1790342214387,"version":"4.1.0"},"reference-count":17,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"unspecified","delay-in-days":139,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004337","name":"F. Hoffmann-La Roche Ltd","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2025,4,5]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) and the Systemic Lupus Erythematosus Responder Index 4 (SRI4) responses are the most common primary endpoints in SLE clinical trials. We examined the concordance and the reasons for discordance in BICLA\/SRI4 responses in participants with SLE receiving placebo and standard of care (SOC) in two randomised controlled trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This post-hoc analysis included data from the placebo arm (participants treated with SOC) of the EXPLORER (n=87; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT00137969\">NCT00137969<\/jats:ext-link>) and ATHOS (n=80; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02908100\">NCT02908100<\/jats:ext-link>) trials. Disease activity was measured using BILAG and SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index) in the EXPLORER trial and BILAG-2004 and SLEDAI-2000K in the ATHOS trial. For this analysis, participants were classified as responders or non-responders based on BICLA and SRI4 and the presence of intercurrent events. Concordance and discordance frequencies between BICLA and SRI4 were determined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In EXPLORER, the BICLA response rates were lower than the SRI4 response rates (29.9% vs 41.4% at week 52, respectively), whereas in ATHOS the BICLA and SRI4 response rates were similar (41.2% vs 43.8% at week 48, respectively). The overall BICLA\/SRI4 concordance (Cohen\u2019s \u03ba score) was moderate (0.46 in EXPLORER and 0.54 in ATHOS at weeks 52 and 48, respectively). At weeks 52 and 48, BICLA+\/SRI4\u2212 and BICLA\u2212\/SRI4+ discordance, respectively, was 6.9% and 18.4% in EXPLORER and 10.0% and 12.5% in ATHOS. In an analysis of ATHOS subgroups based on the presence or absence of rash at baseline, BICLA response was higher at week 48 in participants with arthritis only than in those with arthritis and mucocutaneous comanifestations (63.2% vs 33.9%, respectively). BICLA\u2212\/SRI4+ and BICLA+\/SRI4\u2212 discordance was lower in participants with low compared with normal complement at baseline.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>BICLA and SRI4 may be discordant in SLE trials. Arthritis and rash were the primary drivers of the discordance, and serology influenced BICLA and SRI4 response, suggesting the need for evaluation of multiple efficacy endpoints rather than a single measure.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/lupus-2024-001483","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T04:58:08Z","timestamp":1747717088000},"page":"e001483","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluating the concordance between BICLA and SRI4 in patients with systemic lupus erythematosus from the placebo arms of the EXPLORER and ATHOS trials"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct00137969","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02908100","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00137969","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02908100","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-5023","authenticated-orcid":false,"given":"Anca D","family":"Askanase","sequence":"first","affiliation":[{"name":"Columbia University Irving Medical Center, New York University, New York City, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Vital","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Meier","sequence":"additional","affiliation":[{"name":"F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Turchetta","sequence":"additional","affiliation":[{"name":"Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan (Ashley)","family":"Mao","sequence":"additional","affiliation":[{"name":"Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Maller","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A","family":"Ross Terres","sequence":"additional","affiliation":[{"name":"Genentech, Inc, South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dall\u2019Era","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"2025091515191058000_12.1.e001483.1","doi-asserted-by":"crossref","DOI":"10.1136\/lupus-2018-000266","article-title":"Evaluating duration of response to treatment in systemic lupus erythematosus clinical trials","volume":"5","author":"Kim","year":"2018","journal-title":"Lupus Sci Med"},{"key":"2025091515191058000_12.1.e001483.2","unstructured":"Aguirre A , Kim M , Goteti K , et al . SRI-4 and BICLA: How Well Do They Agree Across Trials of Active Systemic Lupus Erythematosus? [abstract]. Arthritis Rheumatol 2022;74. Available: https:\/\/acrabstracts.org\/abstract\/sri-4-and-bicla-how-well-do-they-agree-across-trials-of-active-systemic-lupus-erythematosus\/"},{"key":"2025091515191058000_12.1.e001483.3","doi-asserted-by":"publisher","DOI":"10.1002\/art.27233"},{"key":"2025091515191058000_12.1.e001483.4","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1002\/art.41811","article-title":"Efficacy, Safety, and Pharmacodynamic Effects of the Bruton\u2019s Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial","volume":"73","author":"Isenberg","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"2025091515191058000_12.1.e001483.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23889.x"},{"key":"2025091515191058000_12.1.e001483.6","first-page":"S40","article-title":"The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis","volume":"34","author":"van Riel","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"2025091515191058000_12.1.e001483.7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh624"},{"key":"2025091515191058000_12.1.e001483.8","first-page":"447","article-title":"The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus","volume":"86","author":"Hay","year":"1993","journal-title":"Q J Med"},{"key":"2025091515191058000_12.1.e001483.9","first-page":"S37","article-title":"Measures of adult systemic lupus erythematosus: updated version of British Isles Lupus Assessment Group (BILAG 2004), European Consensus Lupus Activity Measurements (ECLAM), Systemic Lupus Activity Measure, Revised (SLAM-R), Systemic Lupus Activity Questionnaire for Population Studies (SLAQ), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Systemic Lupus International Collaborating Clinics\/American College of Rheumatology Damage Index (SDI)","volume":"63 Suppl 11","author":"Romero-Diaz","year":"2011","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2025091515191058000_12.1.e001483.10","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"2025091515191058000_12.1.e001483.11","doi-asserted-by":"publisher","DOI":"10.1191\/096120399680411281"},{"key":"2025091515191058000_12.1.e001483.12","first-page":"288","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman","year":"2002","journal-title":"J Rheumatol"},{"key":"2025091515191058000_12.1.e001483.13","doi-asserted-by":"crossref","DOI":"10.1136\/lupus-2013-000005","article-title":"Which outcome measures in SLE clinical trials best reflect medical judgment?","volume":"1","author":"Thanou","year":"2014","journal-title":"Lupus Sci Med"},{"key":"2025091515191058000_12.1.e001483.14","doi-asserted-by":"crossref","unstructured":"Mahmoud K , Md Yusof MY , Teh LS , et al . Improving the arthritis component of the SLEDAI-2K. Rheumatology (Oxford) 2024.:keae695. doi:10.1093\/rheumatology\/keae695","DOI":"10.1093\/rheumatology\/keae695"},{"key":"2025091515191058000_12.1.e001483.15","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-eular.702"},{"key":"2025091515191058000_12.1.e001483.16","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1136\/annrheumdis-2021-221847","article-title":"Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2\/3 trials","volume":"81","author":"Bruce","year":"2022","journal-title":"Ann Rheum Dis"},{"key":"2025091515191058000_12.1.e001483.17","doi-asserted-by":"crossref","DOI":"10.1136\/lupus-2020-000459","article-title":"Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme","volume":"8","author":"Maslen","year":"2021","journal-title":"Lupus Sci Med"}],"container-title":["Lupus Science &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/lupus-2024-001483","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:19:20Z","timestamp":1757974760000},"score":1,"resource":{"primary":{"URL":"https:\/\/lupus.bmj.com\/lookup\/doi\/10.1136\/lupus-2024-001483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,5,19]]},"published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1136\/lupus-2024-001483"],"URL":"https:\/\/doi.org\/10.1136\/lupus-2024-001483","relation":{},"ISSN":["2053-8790"],"issn-type":[{"value":"2053-8790","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]}}}