{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T11:29:59Z","timestamp":1782127799756,"version":"3.54.5"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There are numerous non-biologic and biologic disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA). Typical sequences of bDMARDs are not clear. Future treatment policies and trials should be informed by quantitative estimates of current treatment practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from Corrona, a large real-world RA registry, to develop a method for quantifying sequential patterns in treatment with bDMARDs. As a proof of concept, we study patients who eventually use tocilizumab monotherapy (TCZm), an IL-6 antagonist with similar benefits used as monotherapy or in combination. Patients starting a bDMARD were included and were followed using a discrete-state Markov model, observing changes in treatments every 6\u00a0months and determining whether they used TCZm. A supervised machine learning algorithm was then employed to determine longitudinal patient factors associated with TCZm use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>7300 patients starting a bDMARD were followed for up to 5\u2009years. Their median age was 58\u2009years, 78% were female, median disease duration was 5\u2009years, and 57% were seropositive. During follow-up, 287 (3.9%) reported use of TCZm with median time until use of 25.6 (11.5, 56.0) months. Eighty-two percent of TCZm use began within 3\u00a0years of starting any bDMARD. Ninety-three percent of TCZm users switched from TCZ combination, a TNF inhibitor, or another bDMARD. Very few patients are given TCZm as their first DMARD (0.6%). Variables associated with the use of TCZm included prior use of TCZ combination therapy, older age, longer disease duration, seronegative, higher disease activity, and no prior use of a TNF inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Improved understanding of treatment sequences in RA may help personalize care. These methods may help optimize treatment decisions using large-scale real-world data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-020-02408-4","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T07:04:27Z","timestamp":1610607867000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The sequence of disease-modifying anti-rheumatic drugs: pathways to and predictors of tocilizumab monotherapy"],"prefix":"10.1186","volume":"23","author":[{"given":"Daniel H.","family":"Solomon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyoung C.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Losina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Yau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik D.","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"issue":"13","key":"2408_CR1","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2018.13103","volume":"320","author":"D Aletaha","year":"2018","unstructured":"Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320(13):1360\u201372.","journal-title":"JAMA."},{"issue":"4","key":"2408_CR2","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1136\/annrheumdis-2018-213678","volume":"78","author":"Y Okada","year":"2019","unstructured":"Okada Y, Eyre S, Suzuki A, Kochi Y, Yamamoto K. Genetics of rheumatoid arthritis: 2018 status. Ann Rheum Dis. 2019;78(4):446\u201353.","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"2408_CR3","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1136\/annrheumdis-2016-210711","volume":"76","author":"K Chatzidionysiou","year":"2017","unstructured":"Chatzidionysiou K, Emamikia S, Nam J, Ramiro S, Smolen J, van der Heijde D, et al. Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis. 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The Western IRB oversees ethical approval of the Corrona registry.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DHS received research grants from Abbvie, Amgen, Janssen, and Corrona. SCK received research grants from Pfizer, Roche, AbbVie, and Bristol-Myers Squibb to Brigham and Women\u2019s Hospital. VY is an employee of Genentech\/Roche.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}