{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:22:20Z","timestamp":1787008940981,"version":"build-2736575974"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["137137"],"award-info":[{"award-number":["137137"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ontario Ministry of Health and Long-term Care Drug Innovation","award":["2010-001"],"award-info":[{"award-number":["2010-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anti\u2013tumor necrosis factor\u2013\u03b1 (anti-TNF-\u03b1) treatments are increasingly used to treat pediatric Crohn\u2019s disease, even without a prior trial of immunomodulators, but the cost-effectiveness of such treatment algorithms has not been formally examined. Drug plan decision-makers require evidence of cost-effectiveness to inform funding decisions. The objective was to assess the incremental cost-effectiveness of early intervention with anti-TNF-\u03b1 treatment vs a conventional step-up strategy per steroid-free remission-week gained from public health care and societal payer perspectives over 3 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A probabilistic microsimulation model was constructed for children with newly diagnosed moderate to severe Crohn\u2019s disease receiving anti-TNF-\u03b1 treatment and concomitant treatments within the first 3 months of diagnosis compared with children receiving standard care consisting of steroids and\/or immunomodulators with the possibility of anti-TNF-\u03b1 treatment after 3 months of diagnosis. A North American multicenter observational study with 360 patients provided input into clinical outcomes and health care resource use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Early intervention with anti-TNF-\u03b1 treatment was more costly, with an incremental cost of CAD$31,112 (95% confidence interval [CI], $2939\u2013$91,715), and more effective, with 11.3 more weeks in steroid-free remission (95% CI, 10.6\u201311.6) compared with standard care, resulting in an incremental cost per steroid-free remission-week gained of CAD$2756 from an Ontario public health care perspective and CAD$2968 from a societal perspective. The incremental cost-effectiveness ratio was sensitive to the price of infliximab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results suggest that although early anti-TNF-\u03b1 was not cost-effective, it was clinically beneficial. These findings, along with other randomized controlled trial evidence, may inform formulary decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izz267","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T20:50:40Z","timestamp":1573764640000},"page":"1239-1250","source":"Crossref","is-referenced-by-count":11,"title":["Cost-effectiveness and Clinical Outcomes of Early Anti\u2013Tumor Necrosis Factor\u2013\u03b1 Intervention in Pediatric Crohn\u2019s Disease"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-6189","authenticated-orcid":false,"given":"Naazish S","family":"Bashir","sequence":"first","affiliation":[{"name":"Program of Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada"},{"name":"The Institute of Health Policy, Management and Evaluation, The University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D","family":"Walters","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada"},{"name":"Division of Clinical Pharmacology, Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy J","family":"Ungar","sequence":"additional","affiliation":[{"name":"Program of Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada"},{"name":"The Institute of Health Policy, Management and Evaluation, The University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"2020071623321212800_CIT0001","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/ibd.21349","article-title":"Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends","volume":"17","author":"Benchimol","year":"2011","journal-title":"Inflamm Bowel Dis."},{"key":"2020071623321212800_CIT0002","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1097\/MOP.0b013e3283574154","article-title":"The use of biologic agents in pediatric inflammatory bowel disease","volume":"24","author":"Yang","year":"2012","journal-title":"Curr Opin Pediatr."},{"key":"2020071623321212800_CIT0003","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1053\/j.gastro.2016.09.046","article-title":"Management strategies to improve outcomes of patients with inflammatory bowel diseases","volume":"152","author":"Colombel","year":"2017","journal-title":"Gastroenterology."},{"key":"2020071623321212800_CIT0004","article-title":"Guidelines for the medical management of pediatric luminal Crohn\u2019s disease from the Canadian children inflammatory bowel disease network and the Canadian Association of Gastroenterology Toronto Consensus","author":"Mack","journal-title":"Gastroenterology."},{"key":"2020071623321212800_CIT0005","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1053\/j.gastro.2013.10.027","article-title":"Increased effectiveness of early therapy with anti-tumor necrosis factor-\u03b1 vs an immunomodulator in children with Crohn\u2019s disease","volume":"146","author":"Walters","year":"2014","journal-title":"Gastroenterology."},{"key":"2020071623321212800_CIT0006","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1097\/MIB.0000000000000083","article-title":"Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn\u2019s disease","volume":"20","author":"Church","year":"2014","journal-title":"Inflamm Bowel Dis."},{"key":"2020071623321212800_CIT0007","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/S0140-6736(08)60304-9","article-title":"Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn\u2019s disease: an open randomised trial","volume":"371","author":"D\u2019Haens","year":"2008","journal-title":"Lancet."},{"key":"2020071623321212800_CIT0008","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1053\/j.gastro.2009.09.056","article-title":"Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn\u2019s disease","volume":"138","author":"Baert","year":"2010","journal-title":"Gastroenterology."},{"key":"2020071623321212800_CIT0009","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/S0140-6736(15)00068-9","article-title":"Early combined immunosuppression for the management of Crohn\u2019s disease (REACT): a cluster randomised controlled trial","volume":"386","author":"Khanna","year":"2015","journal-title":"Lancet."},{"key":"2020071623321212800_CIT0010","first-page":"67","article-title":"Early treatment in Crohn\u2019s disease: do we have enough evidence to reverse the therapeutic pyramid?","volume":"21","author":"Spurio","year":"2012","journal-title":"J Gastrointestin Liver Dis."},{"key":"2020071623321212800_CIT0011","first-page":"413","article-title":"Is top-down therapy a more effective alternative to conventional step-up therapy for Crohn\u2019s disease?","volume":"31","author":"Tsui","year":"2018","journal-title":"Ann Gastroenterol."},{"key":"2020071623321212800_CIT0012","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1097\/MIB.0b013e3182916046","article-title":"A systematic review of economic studies on biological agents used to treat Crohn\u2019s disease","volume":"19","author":"Tang","year":"2013","journal-title":"Inflamm Bowel Dis."},{"key":"2020071623321212800_CIT0013","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/jcag\/gwy008.104","article-title":"A103 early initiation of anti-TNF therapy is cost-saving compared to late initiation for patients with Crohn\u2019s disease","volume":"1","author":"Beilman","year":"2018","journal-title":"J Can Assoc Gastroenterol."},{"key":"2020071623321212800_CIT0014","volume-title":"Guidelines for the Economic Evaluation of Health Technologies: Canada","author":"Canadian Agency for Drugs and Technologies in Health (CADTH)","year":"2017","edition":"4th ed"},{"key":"2020071623321212800_CIT0015","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/acprof:oso\/9780190492939.003.0003","article-title":"Recommendations on perspectives for the reference case.","volume-title":"Cost-Effectiveness in Health and Medicine","author":"Neumann","year":"2016"},{"key":"2020071623321212800_CIT0016","volume-title":"Guide to the Methods of Technology Appraisal 2013","author":"National Institute of Health and Care Excellence (NICE)","year":"2013"},{"key":"2020071623321212800_CIT0017","first-page":"3","article-title":"The uniqueness of child health and challenges to measuring costs and consequences.","volume-title":"Economic Evaluation in Child Health","author":"Ungar","year":"2010"},{"key":"2020071623321212800_CIT0018","author":"Kugathasan"},{"key":"2020071623321212800_CIT0019","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1136\/archdischild-2013-305214","article-title":"Surgery for children with Crohn\u2019s disease: indications, complications and outcome","volume":"99","author":"Blackburn","year":"2014","journal-title":"Arch Dis Child."},{"key":"2020071623321212800_CIT0020"},{"key":"2020071623321212800_CIT0021","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198529446.001.0001","volume-title":"Methods for the Economic Evaluation of Health Care Programmes","author":"Drummond","year":"2005"},{"key":"2020071623321212800_CIT0022","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1177\/0272989X0002000308","article-title":"Representing both first- and second-order uncertainties by Monte Carlo simulation for groups of patients","volume":"20","author":"Halpern","year":"2000","journal-title":"Med Decis Making."},{"key":"2020071623321212800_CIT0023","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/hec.1199","article-title":"Monte Carlo probabilistic sensitivity analysis for patient level simulation models: efficient estimation of mean and variance using ANOVA","volume":"16","author":"O\u2019Hagan","year":"2007","journal-title":"Health Econ."},{"key":"2020071623321212800_CIT0024","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.cgh.2014.01.021","article-title":"Risks of serious infection or lymphoma with anti-tumor necrosis factor therapy for pediatric inflammatory bowel disease: a systematic review","volume":"12","author":"Dulai","year":"2014","journal-title":"Clin Gastroenterol Hepatol."},{"key":"2020071623321212800_CIT0025","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1185\/03007995.2010.547575","article-title":"Safety and efficacy of maintenance infliximab therapy for moderate-to-severe Crohn\u2019s disease in children: REACH open-label extension","volume":"27","author":"Hyams","year":"2011","journal-title":"Curr Med Res Opin."},{"key":"2020071623321212800_CIT0026","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s00384-007-0281-3","article-title":"Surgical intervention in children with Crohn\u2019s disease","volume":"22","author":"Leonor","year":"2007","journal-title":"Int J Colorectal Dis."},{"key":"2020071623321212800_CIT0027","volume-title":"Canadian Cancer Statistics 2017","author":"Canadian Cancer Society\u2019s Advisory Committee on Cancer Statistics","year":"2017"},{"key":"2020071623321212800_CIT0028","first-page":"1","article-title":"CDC growth charts: United States","volume":"314","author":"Kuczmarski","year":"2000","journal-title":"Adv Data."},{"key":"2020071623321212800_CIT0029","volume-title":"Guidelines for the Administration of Enteral and Parenteral Nutrition in Paediatrics","author":"Aquilina","year":"2007","edition":"3rd ed"},{"key":"2020071623321212800_CIT0030","volume-title":"Table 14-10-0320-02 Average Usual Hours and Wages by Selected Characteristics, Monthly, Unadjusted for Seasonality (x 1000)","author":"Statistics Canada","year":"2014"},{"key":"2020071623321212800_CIT0031","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.crohns.2014.04.005","article-title":"Consensus guidelines of ECCO\/ESPGHAN on the medical management of pediatric Crohn\u2019s disease","volume":"8","author":"Ruemmele","year":"2014","journal-title":"J Crohns Colitis."},{"key":"2020071623321212800_CIT0032","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/MPG.0b013e31825959b8","article-title":"Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations","volume":"55","author":"Rufo","year":"2012","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"2020071623321212800_CIT0033","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1651-2227.2010.01938.x","article-title":"Infliximab therapy in children with Crohn\u2019s disease: a one-year evaluation of efficacy comparing \u2018top-down\u2019 and \u2018step-up\u2019 strategies","volume":"100","author":"Kim","year":"2011","journal-title":"Acta Paediatr."},{"key":"2020071623321212800_CIT0034","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1097\/MPG.0000000000000711","article-title":"Infliximab \u201ctop-down\u201d strategy is superior to \u201cstep-up\u201d in maintaining long-term remission in the treatment of pediatric Crohn disease","volume":"60","author":"Lee","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr."},{"key":"2020071623321212800_CIT0035","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1053\/j.gastro.2014.06.023","article-title":"Incidence, outcomes, and health services burden of very early onset inflammatory bowel disease","volume":"147","author":"Benchimol","year":"2014","journal-title":"Gastroenterology."},{"key":"2020071623321212800_CIT0036","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1136\/gutjnl-2014-307008","article-title":"Outcome measures for clinical trials in paediatric IBD: an evidence-based, expert-driven practical statement paper of the paediatric ECCO committee","volume":"64","author":"Ruemmele","year":"2015","journal-title":"Gut."},{"key":"2020071623321212800_CIT0037","doi-asserted-by":"crossref","first-page":"13219","DOI":"10.3748\/wjg.v20.i37.13219","article-title":"Crohn\u2019s disease and growth deficiency in children and adolescents","volume":"20","author":"Gasparetto","year":"2014","journal-title":"World J Gastroenterol."},{"key":"2020071623321212800_CIT0038","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1002\/ibd.20378","article-title":"Guidelines for the management of growth failure in childhood inflammatory bowel disease","volume":"14","author":"Heuschkel","year":"2008","journal-title":"Inflamm Bowel Dis."},{"key":"2020071623321212800_CIT0039","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1136\/gutjnl-2012-302830","article-title":"Mucosal healing in inflammatory bowel diseases: a systematic review","volume":"61","author":"Neurath","year":"2012","journal-title":"Gut."},{"key":"2020071623321212800_CIT0040","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1053\/j.gastro.2007.05.051","article-title":"Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort","volume":"133","author":"Fr\u00f8slie","year":"2007","journal-title":"Gastroenterology."},{"key":"2020071623321212800_CIT0041","first-page":"1","article-title":"Economic evaluations of treatments for inflammatory bowel diseases: a literature review","volume":"2018","author":"Lachaine","year":"2018","journal-title":"Can J Gastroenterol Hepatol."},{"key":"2020071623321212800_CIT0042","doi-asserted-by":"crossref","first-page":"e0145087","DOI":"10.1371\/journal.pone.0145087","article-title":"A Systematic review of the cost-effectiveness of biologics for the treatment of inflammatory bowel diseases","volume":"10","author":"Huoponen","year":"2015","journal-title":"PLoS One."},{"key":"2020071623321212800_CIT0043","doi-asserted-by":"crossref","first-page":"e0185500","DOI":"10.1371\/journal.pone.0185500","article-title":"A systematic review of cost-effectiveness studies comparing conventional, biological and surgical interventions for inflammatory bowel disease","volume":"12","author":"Pillai","year":"2017","journal-title":"PLoS One."},{"key":"2020071623321212800_CIT0044","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1524-4733.2009.00658.x","article-title":"Cost-effectiveness of scheduled maintenance treatment with infliximab for pediatric Crohn\u2019s disease","volume":"13","author":"Punekar","year":"2010","journal-title":"Value Health."},{"key":"2020071623321212800_CIT0045","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.crohns.2011.07.007","article-title":"Canadian cost-utility analysis of initiation and maintenance treatment with anti-TNF-\u03b1 drugs for refractory Crohn\u2019s disease","volume":"6","author":"Blackhouse","year":"2012","journal-title":"J Crohns Colitis."},{"key":"2020071623321212800_CIT0046","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1097\/00054725-200810001-00005","article-title":"Inflammatory bowel disease: the difference between children and adults","volume":"14","author":"Kelsen","year":"2008","journal-title":"Inflamm Bowel Dis."},{"key":"2020071623321212800_CIT0047","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2165\/11591570-000000000-00000","article-title":"Challenges in health state valuation in paediatric economic evaluation: are QALYs contraindicated?","volume":"29","author":"Ungar","year":"2011","journal-title":"Pharmacoeconomics."},{"key":"2020071623321212800_CIT0048","volume-title":"Ontario Public Drug Programs","author":"Office of the Auditor General of Ontario","year":"2017"}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ibdjournal\/article-pdf\/26\/8\/1239\/33505028\/izz267.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ibdjournal\/article-pdf\/26\/8\/1239\/33505028\/izz267.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T19:32:50Z","timestamp":1722022370000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/26\/8\/1239\/5625872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,15]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,11,15]]},"published-print":{"date-parts":[[2020,7,17]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izz267","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,8]]},"published":{"date-parts":[[2019,11,15]]}}}