{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:55:55Z","timestamp":1782496555928,"version":"3.54.5"},"reference-count":29,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031688","name":"Pfizer Pharma GmbH","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100031688","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,1,27]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify predictors of treatment changes and to evaluate the effectiveness and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) initiating tofacitinib in a real-world setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>The non-interventional study ESCALATE-RA included 1518 patients with RA from Germany. RA treatment, including all changes in therapy, was documented for 24 months starting from the initial intake of tofacitinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>All patients started with tofacitinib therapy, either as monotherapy or in combination with methotrexate (MTX).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary and secondary outcome measures<\/jats:title>\n                    <jats:p>The impact of several factors of interest on the number and timing of treatment changes was assessed as primary outcome using Cox proportional hazards models. Further outcomes were tofacitinib drug survival and the use of follow-up disease-modifying antirheumatic drugs after first treatment change. We also assessed the effectiveness, concomitant glucocorticoid (GC) use, PROs (such as functional ability, patient satisfaction, pain and quality of life) and safety. Analyses were based on observed data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\u2018Lack of efficacy\u2019 (HR 3.30) and \u2018intolerance\u2019 (HR 4.43) leading to termination of tofacitinib were key factors favouring therapy changes. Higher patient satisfaction was significantly associated with a reduced likelihood of treatment changes (HR 0.82). Increasing GC doses were associated with a higher probability of step-up\/switch changes (HR 1.21). The estimated tofacitinib drug survival was 48% at the end of study. Proportions of patients achieving low disease activity (both Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) \u039462%) and remission (SDAI \u039425%, CDAI \u039428%) increased from baseline under tofacitinib and were comparable between monotherapy and combination therapy with MTX. Mean concomitant GC dose decreased (2 mg\/day). PROs indicated reduced pain and fatigue, while functional ability and quality of life improved. 63.9% of the patients experienced a treatment-emergent adverse event (AE), 8.8% a treatment-emergent AE of special interest and deaths occurred in 0.5%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Key factors for therapy changes in patients with RA treated with tofacitinib were lack of efficacy and intolerance. Higher patient satisfaction was associated with a reduced probability of treatment changes, while increased GC doses led to a higher likelihood of step-ups\/switches. Patients demonstrated a marked reduction in disease activity for up to 24 months, along with improvements in functional ability, pain and quality of life. Observed AEs were consistent with the known safety profile of tofacitinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03387423\">NCT03387423<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-096952","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:40:52Z","timestamp":1770907252000},"page":"e096952","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Tofacitinib in rheumatoid arthritis: a German real-world study with focus on treatment changes, effectiveness and patient-reported outcomes (ESCALATE-RA)"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct03387423","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03387423","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00413699","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00661661","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7364-0605","authenticated-orcid":false,"given":"Klaus","family":"Krueger","sequence":"first","affiliation":[{"name":"Rheumatologisches Praxiszentrum, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8750-7186","authenticated-orcid":false,"given":"Frank","family":"Behrens","sequence":"additional","affiliation":[{"name":"Centrum f\u00fcr innovative Diagnostik und Therapie Rheumatologie\/Immunologie, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Brandt-Juergens","sequence":"additional","affiliation":[{"name":"Rheumatologische Schwerpunktpraxis, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Detert","sequence":"additional","affiliation":[{"name":"Rheumatologisch-immunologische Praxis, Templin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Feuchtenberger","sequence":"additional","affiliation":[{"name":"Rheumatology, MVZ MED BAYERN OST, Burghausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Prothmann","sequence":"additional","affiliation":[{"name":"Krankenhaus P\u00fcttlingen, Knappschaftsklinikum Saar GmbH, P\u00fcttlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Behmer","sequence":"additional","affiliation":[{"name":"Pfizer Pharma GmbH, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jean Marianne","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Pfizer Pharma GmbH, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Jobst","sequence":"additional","affiliation":[{"name":"Pfizer Pharma GmbH, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Klaus","sequence":"additional","affiliation":[{"name":"Pfizer Pharma GmbH, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meng","sequence":"additional","affiliation":[{"name":"Pfizer Pharma GmbH, Berlin, 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SmPC summary of product characteristics xeljanz inn-tofacitinib citrate. 2023."},{"key":"2026062610412590000_16.2.e096952.14","doi-asserted-by":"crossref","DOI":"10.1186\/s12874-015-0005-2","article-title":"Simulating recurrent event data with hazard functions defined on a total time scale","volume":"15","author":"Jahn-Eimermacher","year":"2015","journal-title":"BMC Med Res Methodol"},{"key":"2026062610412590000_16.2.e096952.15","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/68.2.373"},{"key":"2026062610412590000_16.2.e096952.16","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2020-001290","article-title":"Factors associated with treatment satisfaction in patients with rheumatoid arthritis: data from the biological register RABBIT","volume":"6","author":"Sch\u00e4fer","year":"2020","journal-title":"RMD Open"},{"key":"2026062610412590000_16.2.e096952.17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2147\/PPA.S289692","article-title":"Treatment Satisfaction, Patient Preferences, and the Impact of Suboptimal Disease Control in a Large International Rheumatoid Arthritis Cohort: SENSE Study","volume":"15","author":"Taylor","year":"2021","journal-title":"Patient Prefer Adherence"},{"key":"2026062610412590000_16.2.e096952.18","doi-asserted-by":"publisher","DOI":"10.1002\/art.22719"},{"key":"2026062610412590000_16.2.e096952.19","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/acr2.1010","article-title":"Persistence of Tofacitinib in the Treatment of Rheumatoid Arthritis in Open-Label, Long-Term Extension Studies up to 9.5 Years","volume":"1","author":"Pope","year":"2019","journal-title":"ACR Open Rheumatol"},{"key":"2026062610412590000_16.2.e096952.20","first-page":"568","article-title":"Experience with tofacitinib in Canada: patient characteristics and treatment patterns in rheumatoid arthritis over 3 years","volume":"59","author":"Pope","year":"2020","journal-title":"Rheumatology (Oxford)"},{"key":"2026062610412590000_16.2.e096952.21","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222835"},{"key":"2026062610412590000_16.2.e096952.22","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1007\/s10067-020-05021-7","article-title":"Real-world evaluation of effectiveness, persistence, and usage patterns of tofacitinib in treatment of rheumatoid arthritis in Australia","volume":"39","author":"Bird","year":"2020","journal-title":"Clin Rheumatol"},{"key":"2026062610412590000_16.2.e096952.23","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.2023-0752"},{"key":"2026062610412590000_16.2.e096952.24","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1241954","article-title":"Risk of herpes zoster associated with JAK inhibitors in immune-mediated inflammatory diseases: a systematic review and network meta-analysis","volume":"14","author":"Xu","year":"2023","journal-title":"Front Pharmacol"},{"key":"2026062610412590000_16.2.e096952.25","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1002\/art.38745","article-title":"Herpes Zoster and Tofacitinib Therapy in Patients With Rheumatoid Arthritis","volume":"66","author":"Winthrop","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"2026062610412590000_16.2.e096952.26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"2026062610412590000_16.2.e096952.27","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223715"},{"key":"2026062610412590000_16.2.e096952.28","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222259"},{"key":"2026062610412590000_16.2.e096952.29","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2023-003489","article-title":"Risk of major adverse cardiovascular events in patients with rheumatoid arthritis treated with conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs: observational data from the German RABBIT register","volume":"9","author":"Meissner","year":"2023","journal-title":"RMD Open"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-096952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:43:58Z","timestamp":1782495838000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-096952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,12]]},"published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1136\/bmjopen-2024-096952"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-096952","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]}}}