{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:41:04Z","timestamp":1791942064762,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We assess the clinical and structural impact at two years of progressively spacing tocilizumab (TCZ) or abatacept (ABA) injections versus maintenance at full dose in patients with rheumatoid arthritis in sustained remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter open\u2010label noninferiority (NI) randomized clinical trial included patients with established rheumatoid arthritis in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance (M) at full dose (M\u2010arm) or progressive injection spacing (S) driven by the Disease Activity Score in 28 joints every 3 months up to biologics discontinuation (S\u2010arm). The primary end point was the evolution of disease activity according to the Disease Activity Score in 44 joints during the 2\u2010year follow\u2010up analyzed per protocol with a linear mixed\u2010effects model, evaluated by an NI test based on the one\u2010sided 95% confidence interval (95% CI) of the slope difference (NI margin 0.25). Other end points were flare incidence and structural damage progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 202 of the 233 patients included were considered for per protocol analysis (90 in S\u2010arm and 112 in M\u2010arm). At the end of follow\u2010up, 16.2% of the patients in the S\u2010arm could discontinue their biologic disease\u2010modifying antirheumatic drug, 46.9% tapered the dose and 36.9% returned to a full dose. NI was not demonstrated for the primary outcome, with a slope difference of 0.10 (95% CI 0.10\u20130.31) between the two arms. NI was not demonstrated for flare incidence (difference 42.6%, 95% CI 30.0\u201355.1) or rate of structural damage progression at two years (difference 13.9%, 95% CI \u22126.7 to 34.4).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The Towards the Lowest Efficacious Dose trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42752","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T05:39:29Z","timestamp":1699508369000},"page":"541-552","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized\n                    <scp>Open\u2010Label<\/scp>\n                    Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-3183","authenticated-orcid":false,"given":"Joanna","family":"Kedra","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Institut Pierre Louis d'Epid\u00e9miologie et de Sant\u00e9 Publique, AP\u2010HP, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Dieud\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris Cit\u00e9, INSERM UMR 1152 and H\u00f4pital Bichat\u2010Claude Bernard, AP\u2010HP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Giboin","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Institut Pierre Louis d'Epid\u00e9miologie et de Sant\u00e9 Publique, AP\u2010HP, H\u00f4pital Piti\u00e9 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