{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:06:45Z","timestamp":1784002005072,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Canadian Institutes of Health Research New Investigator Salary Award"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp;amp; Research"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Randomized controlled trials (<jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s) exist along a spectrum, from explanatory, designed to evaluate interventions under ideal conditions, to pragmatic, designed to reflect usual care. This study assessed the pragmatism of <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s of advanced therapeutics in rheumatoid arthritis (<jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review was conducted to identify <jats:styled-content style=\"fixed-case\">RA RCT<\/jats:styled-content>s comparing biologic or targeted synthetic therapy in combination with methotrexate, to placebo or any other disease\u2010modifying antirheumatic drugs (<jats:styled-content style=\"fixed-case\">DMARD<\/jats:styled-content>s). Trials were rated using the Pragmatic Explanatory Continuum Indicator Summary\u20102 (<jats:styled-content style=\"fixed-case\">PRECIS<\/jats:styled-content>\u20102) tool in 9 domains, each rated from 1 (very explanatory) to 5 (very pragmatic). Latent class and regression analyses examined the heterogeneity in <jats:styled-content style=\"fixed-case\">PRECIS<\/jats:styled-content>\u20102 scores and the relationship to trial characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 96 trials were included. Eligibility, follow\u2010up, and flexibility of delivery of the intervention were rated as explanatory, with mean \u00b1 <jats:styled-content style=\"fixed-case\">SD PRECIS<\/jats:styled-content>\u20102 scores of 2.0 \u00b1 0.7, 2.0 \u00b1 1.1, and 2.1 \u00b1 0.7, respectively, reflecting strict inclusion criteria, intensive follow\u2010up, and rigid protocols. Studies were rated as pragmatic in setting (3.6 \u00b1 1.5) because many were international, multicenter trials, and in primary analysis (4.1 \u00b1 1.3), because most used intent\u2010to\u2010treat analyses. In latent class analyses, 2 groups were identified; the majority (74%) were rated as explanatory for most domains assessed. These trials had larger sample sizes, were more likely to be industry\u2010funded, and enrolled patients with higher Disease Activity Score in 28 joints and Health Assessment Questionnaire disability index scores, but were less likely to be at high risk of bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s of biologic <jats:styled-content style=\"fixed-case\">DMARD<\/jats:styled-content> treatment in combination with methotrexate for <jats:styled-content style=\"fixed-case\">RA<\/jats:styled-content> were rated as predominantly explanatory, which may affect the generalizability of trial results to clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.23620","type":"journal-article","created":{"date-parts":[[2018,6,15]],"date-time":"2018-06-15T22:34:41Z","timestamp":1529102081000},"page":"620-628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pragmaticism of Randomized Controlled Trials of Biologic Treatment With Methotrexate in Rheumatoid Arthritis: A\u00a0Systematic Review"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3760-2737","authenticated-orcid":false,"given":"May Y.","family":"Choi","sequence":"first","affiliation":[{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3761-237X","authenticated-orcid":false,"given":"Cheryl","family":"Barnabe","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine University of Calgary, 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