{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:40:26Z","timestamp":1792168826915,"version":"4.4.0"},"reference-count":82,"publisher":"National Institute for Health and Care Research","issue":"15","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["09\/51\/01"],"award-info":[{"award-number":["09\/51\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"crossref","award":["19612"],"award-info":[{"award-number":["19612"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006483","name":"AbbVie Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sharp Clinical Services"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"\n Background<\/jats:title>\n Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira\u00ae<\/jats:sup>; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n This was a randomised (applying a ratio of 2\u2009:\u20091 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost\u2013utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n The setting was tertiary care centres throughout the UK.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n Patients aged 2\u201318 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks).<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n All participants received a stable dose of MTX and either adalimumab (20\u2009mg\/0.8\u2009ml for patients weighing <\u200930\u2009kg or 40\u2009mg\/0.8\u2009ml for patients weighing \u2265\u200930\u2009kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8\u2009ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months.<\/jats:p>\n <\/jats:sec>\n \n Main outcome measures<\/jats:title>\n Primary outcome \u2013 time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome \u2013 incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 90 participants were randomised (adalimumab, n<\/jats:italic>\u2009=\u200960; placebo, n<\/jats:italic>\u2009=\u200930). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p<\/jats:italic>\u2009<\u20090.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was \u00a3129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is <\u20091% at the \u00a330,000-per-QALY threshold.<\/jats:p>\n <\/jats:sec>\n \n Future work<\/jats:title>\n A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified.<\/jats:p>\n <\/jats:sec>\n \n Trial registration<\/jats:title>\n Current Controlled Trials ISRCTN10065623 and European Clinical Trials Database number 2010-021141-41.<\/jats:p>\n <\/jats:sec>\n \n Funding<\/jats:title>\n This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment<\/jats:italic>; Vol. 23, No. 15. See the NIHR Journals Library website for further project information. This trial was also funded by Arthritis Research UK (grant reference number 19612). Two strengths of adalimumab (20\u2009mg\/0.8\u2009ml and 40\u2009mg\/0.8\u2009ml) and a matching placebo were manufactured by AbbVie Inc. (the Marketing Authorisation holder) and supplied in bulk to the contracted distributor (Sharp Clinical Services, Crickhowell, UK) for distribution to trial centres.<\/jats:p>\n <\/jats:sec>","DOI":"10.3310\/hta23150","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T07:55:17Z","timestamp":1554882917000},"page":"1-140","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT"],"prefix":"10.3310","volume":"23","clinical-trial-number":[{"clinical-trial-number":"isrctn10065623","registry":"10.18810\/isrctn","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8663-2401","authenticated-orcid":true,"given":"Athimalaipet V","family":"Ramanan","sequence":"first","affiliation":[{"name":"Department of Paediatric Rheumatology, University Hospitals Bristol NHS 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