{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:43:37Z","timestamp":1784634217211,"version":"3.55.0"},"reference-count":174,"publisher":"National Institute for Health and Care Research","issue":"34","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"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":["14\/64\/01"],"award-info":[{"award-number":["14\/64\/01"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objective<\/jats:title><jats:p>To assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs [etanercept (Enbrel<jats:sup>\u00ae<\/jats:sup>, Pfizer), abatacept (Orencia<jats:sup>\u00ae<\/jats:sup>, Bristol-Myers Squibb), adalimumab (Humira<jats:sup>\u00ae<\/jats:sup>, AbbVie) and tocilizumab (RoActemra<jats:sup>\u00ae<\/jats:sup>, Roche) \u2013 with or without methotrexate where indicated] for the treatment of JIA (systemic or oligoarticular JIA are excluded).<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Data sources<\/jats:title><jats:p>Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Review methods<\/jats:title><jats:p>Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost\u2013utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Results<\/jats:title><jats:p>Four placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost\u2013utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were \u00a338,127, \u00a332,526 and \u00a338,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was \u00a339,536 per QALY.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Limitations<\/jats:title><jats:p>The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Conclusions<\/jats:title><jats:p>Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Study registration<\/jats:title><jats:p>This study is registered as PROSPERO CRD42015016459.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Funding<\/jats:title><jats:p>The National Institute for Health Research Health Technology Assessment programme.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta20340","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T09:11:42Z","timestamp":1462439502000},"page":"1-222","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation"],"prefix":"10.3310","volume":"20","author":[{"given":"Jonathan","family":"Shepherd","sequence":"first","affiliation":[{"name":"Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Picot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2016,4]]},"reference":[{"key":"key20160429141245624_ref1-bib1","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1016\/S0140-6736(11)60244-4","article-title":"Juvenile idiopathic arthritis","volume":"377","author":"Prakken","year":"2011","journal-title":"Lancet"},{"key":"key20160429141245624_ref1-bib2","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/S0140-6736(07)60363-8","article-title":"Juvenile idiopathic arthritis","volume":"369","author":"Ravelli","year":"2007","journal-title":"Lancet"},{"key":"key20160429141245624_ref1-bib3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s12016-014-8460-9","article-title":"The etiology of juvenile idiopathic arthritis","volume":"49","author":"Rigante","year":"2015","journal-title":"Clin Rev Allergy Immunol"},{"key":"key20160429141245624_ref1-bib4","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1002\/art.20815","article-title":"Nomenclature and classification in chronic childhood arthritis: time for a change?","volume":"52","author":"Duffy","year":"2005","journal-title":"Arthritis Rheum"},{"key":"key20160429141245624_ref1-bib5","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1546-0096-8-20","article-title":"Burden of childhood-onset arthritis","volume":"8","author":"Moorthy","year":"2010","journal-title":"Pediatr Rheumatol Online J"},{"key":"key20160429141245624_ref1-bib6","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty","year":"2004","journal-title":"J Rheumatol"},{"key":"key20160429141245624_ref1-bib7","volume-title":"What are the Different Types of JIA?","author":"Arthritis Research UK","year":"2014"},{"key":"key20160429141245624_ref1-bib8","volume-title":"Arthritis in Children","author":"Arthritis Care"},{"key":"key20160429141245624_ref1-bib9","volume-title":"My Child has Oligoarticular JIA. 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