{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:04:29Z","timestamp":1793898269942,"version":"4.8.0"},"reference-count":30,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"unspecified","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,8,1]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This 1-year long-term extension (LTE) study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04451772\">NCT04451772<\/jats:ext-link>\n                      ) followed the 48-week phase 2 SLEek study (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03978520\">NCT03978520<\/jats:ext-link>\n                      ) that evaluated upadacitinib (a Janus kinase inhibitor) alone or combined with elsubrutinib (a Bruton\u2019s tyrosine kinase inhibitor) in adults with moderately to severely active systemic lupus erythematosus (SLE). The objective was to evaluate the efficacy and safety of an additional 56 weeks of treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients randomised to upadacitinib 30\u2009mg one time per day (QD) or upadacitinib 30\u2009mg\/elsubrutinib 60\u2009mg QD (upadacitinib\/elsubrutinib) in the SLEek study continued their assigned treatment during the LTE. Patients originally receiving placebo switched to upadacitinib\/elsubrutinib in the LTE. Assessments through week 104 included SLE Responder Index-4 (SRI-4), British Isles Lupus Assessment Group-based Combined Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), change from baseline in glucocorticoid dose, flare events and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This LTE analysis included 127 patients. Efficacy responses for the groups receiving upadacitinib, upadacitinib\/elsubrutinib and placebo to upadacitinib\/elsubrutinib were maintained or increased from weeks 48 to 104 (week 104: SRI-4: 82.1%, 85.4% and 61.3%; BICLA: 69.2%, 78.0% and 54.8%; LLDAS: 60.0%, 78.0% and 34.4%). From weeks 48 through 104, the mean daily glucocorticoid dose was reduced, and the incidence of flares was maintained or further reduced in all treatment groups. Safety profiles were similar to those observed in the primary SLEek study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this LTE study, upadacitinib monotherapy and upadacitinib\/elsubrutinib combined were well tolerated and continued to demonstrate beneficial effects on SLE disease activity, glucocorticoid dose and flares through 104 weeks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005742","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:50:14Z","timestamp":1755589814000},"page":"e005742","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Efficacy and safety of upadacitinib as monotherapy or combined with elsubrutinib for the treatment of systemic lupus erythematosus: results through 104 weeks in a long-term extension study"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04451772","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03978520","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05843643","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03978520","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04451772","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05843643","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Joan T","family":"Merrill","sequence":"first","affiliation":[{"name":"Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Saxena","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, NYU Langone Health, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Aringer","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine III, University Medical Center and Faculty of Medicine, TU Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Cheng","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao T","family":"Doan","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"D\u2019Cruz","sequence":"additional","affiliation":[{"name":"The Louise Coote Lupus Unit, Guy's and St Thomas\u2019 Hospitals NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim R","family":"Masri","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M","family":"D\u2019Silva","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"2025081900500502000_11.3.e005742.1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223035"},{"key":"2025081900500502000_11.3.e005742.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30546-X"},{"key":"2025081900500502000_11.3.e005742.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1100359"},{"key":"2025081900500502000_11.3.e005742.4","doi-asserted-by":"publisher","DOI":"10.1002\/art.30613"},{"key":"2025081900500502000_11.3.e005742.5","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(19)30076-1"},{"key":"2025081900500502000_11.3.e005742.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912196"},{"key":"2025081900500502000_11.3.e005742.7","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)00578-x"},{"key":"2025081900500502000_11.3.e005742.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.42657"},{"key":"2025081900500502000_11.3.e005742.9","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41584-023-00948-y","article-title":"Precision medicine in systemic lupus erythematosus","volume":"19","author":"Fasano","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"2025081900500502000_11.3.e005742.10","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224762"},{"key":"2025081900500502000_11.3.e005742.11","doi-asserted-by":"crossref","first-page":"101814","DOI":"10.1016\/j.berh.2022.101814","article-title":"Systemic lupus erythematosus","volume":"36","author":"Tanaka","year":"2022","journal-title":"Best Practice & Research Clinical Rheumatology"},{"key":"2025081900500502000_11.3.e005742.12","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-222335"},{"key":"2025081900500502000_11.3.e005742.13","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1080\/14397595.2018.1484269","article-title":"ABBV-105, a selective and irreversible inhibitor of Bruton\u2019s tyrosine kinase, is efficacious in multiple preclinical models of inflammation","volume":"29","author":"Goess","year":"2019","journal-title":"Mod Rheumatol"},{"key":"2025081900500502000_11.3.e005742.14","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.662223","article-title":"Bruton\u2019s tyrosine kinase (BTK) inhibitors and autoimmune diseases: making sense of BTK inhibitor specificity profiles and recent clinical trial successes and failures","volume":"12","author":"Ringheim","year":"2021","journal-title":"Front Immunol"},{"key":"2025081900500502000_11.3.e005742.15","first-page":"1518","article-title":"Efficacy and safety of upadacitinib or elsubrutinib alone or in combination for patients with systemic lupus erythematosus: a phase 2 randomized controlled trial","volume":"76","author":"Merrill","year":"2024","journal-title":"Arthritis Rheumatol"},{"key":"2025081900500502000_11.3.e005742.16","doi-asserted-by":"crossref","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum"},{"key":"2025081900500502000_11.3.e005742.17","doi-asserted-by":"publisher","DOI":"10.1002\/art.34473"},{"key":"2025081900500502000_11.3.e005742.18","first-page":"288","article-title":"Systemic lupus erythematosus disease activity index 2000","volume":"29","author":"Gladman","year":"2002","journal-title":"J Rheumatol"},{"key":"2025081900500502000_11.3.e005742.19","first-page":"S885","article-title":"Evaluation of treatment success in systemic lupus erythematosus clinical trials: development of the British Isles Lupus Assessment Group-based Composite Lupus Assessment Endpoint","volume":"63","author":"Wallace","year":"2011","journal-title":"Arthritis Rheum"},{"key":"2025081900500502000_11.3.e005742.20","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207726"},{"key":"2025081900500502000_11.3.e005742.21","first-page":"685","article-title":"Classification and definition of major flares in SLE clinical trials","volume":"8","author":"Petri","year":"1999","journal-title":"Lupus (Los Angel)"},{"key":"2025081900500502000_11.3.e005742.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051135"},{"key":"2025081900500502000_11.3.e005742.23","doi-asserted-by":"publisher","DOI":"10.1002\/art.23130"},{"key":"2025081900500502000_11.3.e005742.24","doi-asserted-by":"publisher","DOI":"10.1002\/art.24698"},{"key":"2025081900500502000_11.3.e005742.25","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202760"},{"key":"2025081900500502000_11.3.e005742.26","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002735","article-title":"Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis","volume":"9","author":"Burmester","year":"2023","journal-title":"RMD Open"},{"key":"2025081900500502000_11.3.e005742.27","doi-asserted-by":"crossref","first-page":"e395","DOI":"10.1016\/S2665-9913(22)00092-3","article-title":"Safety and efficacy of elsubrutinib or upadacitinib alone or in combination (ABBV-599) in patients with rheumatoid arthritis and inadequate response or intolerance to biological therapies: a multicentre, double-blind, randomised, controlled, phase 2 trial","volume":"4","author":"Fleischmann","year":"2022","journal-title":"Lancet Rheumatol"},{"key":"2025081900500502000_11.3.e005742.28","doi-asserted-by":"crossref","DOI":"10.1186\/s12959-015-0043-3","article-title":"Systemic lupus erythematosus and thrombosis","volume":"13","author":"Bazzan","year":"2015","journal-title":"Thromb J"},{"key":"2025081900500502000_11.3.e005742.29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/joim.13557","article-title":"Systemic lupus erythematosus and cardiovascular disease","volume":"293","author":"Frosteg\u00e5rd","year":"2023","journal-title":"J Intern Med"},{"key":"2025081900500502000_11.3.e005742.30","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1111\/all.15261","article-title":"Bruton\u2019s tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions","volume":"77","author":"Mendes-Bastos","year":"2022","journal-title":"Allergy"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2025-005742","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:50:17Z","timestamp":1755589817000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2025-005742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,8,18]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/rmdopen-2025-005742"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2025-005742","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}