{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T12:39:06Z","timestamp":1775479146877,"version":"3.50.1"},"reference-count":123,"publisher":"National Institute for Health and Care Research","issue":"44","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"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":["06\/78\/03"],"award-info":[{"award-number":["06\/78\/03"]}],"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>The efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objective<\/jats:title><jats:p>To compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Method<\/jats:title><jats:p>Between May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5\u2009mg\/kg of intravenous infliximab at 0, 2 and 6 weeks or 2\u2009mg\/kg\/day of intravenous ciclosporin for 7 days followed by 5.5\u2009mg\/kg\/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn\u2019s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1\u20133 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Results<\/jats:title><jats:p>The 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC\/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) \u20130.0088 to 0.0682;<jats:italic>p<\/jats:italic>\u2009=\u20090.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI \u20130.032 to 0.096;<jats:italic>p<\/jats:italic>\u2009=\u20090.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI \u20130.0250 to 0.0353;<jats:italic>p<\/jats:italic>\u2009=\u20090.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;<jats:italic>p<\/jats:italic>\u2009=\u20090.223]; numbers of serious adverse reactions (event ratio\u2009=\u20090.938 favouring ciclosporin, 95% CI 0.590 to 1.493;<jats:italic>p<\/jats:italic>\u2009=\u20090.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;<jats:italic>p<\/jats:italic>\u2009=\u20090.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;<jats:italic>p<\/jats:italic>\u2009=\u20090.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;<jats:italic>p<\/jats:italic>\u2009=\u20090.998); deaths (all three who died received infliximab;<jats:italic>p<\/jats:italic>\u2009=\u20090.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference \u2013\u00a35632, 95% CI \u2013\u00a38305 to \u2013\u00a32773;<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Conclusions<\/jats:title><jats:p>Total cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1\u20133 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN22663589.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the NIHR Health Technology Assessment programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta20440","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T20:08:51Z","timestamp":1466712531000},"page":"1-320","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":51,"title":["Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: pragmatic randomised Trial and economic evaluation (CONSTRUCT)"],"prefix":"10.3310","volume":"20","clinical-trial-number":[{"clinical-trial-number":"isrctn22663589","registry":"10.18810\/isrctn","type":"results"}],"author":[{"given":"John G","family":"Williams","sequence":"first","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Fasihul","family":"Alam","sequence":"additional","affiliation":[{"name":"Swansea Centre for Health Economics, College of Human and Health Science, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laith","family":"Alrubaiy","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare","family":"Clement","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Cohen","sequence":"additional","affiliation":[{"name":"Faculty of Health Sport and Science, University of South Wales, Pontypridd, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Grey","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Hilton","sequence":"additional","affiliation":[{"name":"Patient representative"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayley A","family":"Hutchings","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirella","family":"Longo","sequence":"additional","affiliation":[{"name":"Swansea Centre for Health Economics, College of Human and Health Science, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayne M","family":"Morgan","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances L","family":"Rapport","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne C","family":"Seagrove","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Watkins","sequence":"additional","affiliation":[{"name":"Swansea University Medical School, Swansea University, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2016,6]]},"reference":[{"key":"key20160621143210206_ref1-bib1","doi-asserted-by":"publisher","first-page":"V1","DOI":"10.1136\/gut.2004.043372","article-title":"Guidelines for the management of inflammatory bowel disease in adults","volume":"53","author":"Carter","year":"2004","journal-title":"Gut"},{"key":"key20160621143210206_ref1-bib2","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.1046\/j.1365-2036.2000.00886.x","article-title":"Inflammatory bowel disease: epidemiology and management in an English general practice population","volume":"14","author":"Rubin","year":"2000","journal-title":"Aliment Pharmacol Ther"},{"key":"key20160621143210206_ref1-bib3","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.crohns.2010.02.001","article-title":"The pattern and outcome of acute severe colitis","volume":"4","author":"Dinesen","year":"2010","journal-title":"J Crohns Colitis"},{"key":"key20160621143210206_ref1-bib4","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1136\/bmj.2.4947.1041","article-title":"Cortisone in ulcerative colitis; 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