{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:34:01Z","timestamp":1791531241028,"version":"4.3.4"},"reference-count":27,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment Programme","doi-asserted-by":"publisher","award":["16\/24\/09"],"award-info":[{"award-number":["16\/24\/09"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,12,21]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40\u2009mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>The trial received Research Ethics Committee (REC) approval from South Central \u2013 Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"isrctn\" xlink:href=\"ISRCTN31474800\">ISRCTN31474800<\/jats:ext-link>. Registered 14 April 2020.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-082246","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T04:05:11Z","timestamp":1706155511000},"page":"e082246","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness\u2014a protocol for a randomised controlled trial (ASTUTE trial)"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"isrctn31474800","registry":"10.18810\/isrctn"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9889-4641","authenticated-orcid":false,"given":"Mae","family":"Hazell","sequence":"first","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-9487","authenticated-orcid":false,"given":"Barnaby","family":"Reeves","sequence":"additional","affiliation":[{"name":"University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-2615","authenticated-orcid":false,"given":"Chris A","family":"Rogers","sequence":"additional","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Pike","sequence":"additional","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Culliford","sequence":"additional","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Baos","sequence":"additional","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy P Y","family":"Lui","sequence":"additional","affiliation":[{"name":"Bristol Trials Centre, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A V","family":"Beare","sequence":"additional","affiliation":[{"name":"University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Pavesio","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair K","family":"Denniston","sequence":"additional","affiliation":[{"name":"University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wordsworth","sequence":"additional","affiliation":[{"name":"University of Oxford, University of Oxford, Oxford, UK"},{"name":"NIHR Oxford Biomedical Research Centre, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearse A","family":"Keane","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wilson","sequence":"additional","affiliation":[{"name":"Midlands, NHS England, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Folkard","sequence":"additional","affiliation":[{"name":"Birdshot Uveitis Society, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-0381","authenticated-orcid":false,"given":"Tunde","family":"Peto","sequence":"additional","affiliation":[{"name":"Centre for Public Health, NetwORC UK, Queen\u2019s University Belfast, Belfast, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilakshmi M","family":"Sharma","sequence":"additional","affiliation":[{"name":"Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"},{"name":"NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Dick","sequence":"additional","affiliation":[{"name":"University of Bristol, Bristol, UK"},{"name":"NIHR Biomedical Research Centre, Moorfields and UCL Institute of Ophthalmology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,24]]},"reference":[{"key":"2025101811063539000_14.1.e082246.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2003.06.014"},{"key":"2025101811063539000_14.1.e082246.2","unstructured":"Organization WH . 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