{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:38:19Z","timestamp":1762875499472},"reference-count":42,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2012,12,20]],"date-time":"2012-12-20T00:00:00Z","timestamp":1355961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Immune tolerance induction (<jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>) is recognized as the first choice treatment in haemophilic patients with inhibitors, with the aim of restoring safe and effective standard factor <jats:styled-content style=\"fixed-case\">VIII<\/jats:styled-content> replacement and, particularly, prophylaxis in children. For the latter, literature data and clinical practice support the optimal cost utility ratio of <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>. Indeed, the high success rate, the low incidence of inhibitor recurrence after successful <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> and the possibility of preventing joint deterioration, enable one to predict a considerable long\u2010term reduction of costs in the majority of treated patients. Therefore, in spite of high costs and open issues about optimal regimens, <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> is actually attempted in virtually all children with inhibitors. Few patients with long\u2010standing inhibitors presently undergo <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content>, particularly in the case of severe bleeding tendency. In this setting, uncertainties concerning management are amplified by the paucity of literature data and psychological reluctance by both patients and treaters due to the perceived poor prognosis and the demanding treatment (also in terms of costs). However, clinical data suggest that the role of age at <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> start and of time interval from inhibitor diagnosis, as predictors of <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> outcome, should be considered in a larger framework of proposed and more established prognostic factors. Moreover, optimising <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> management, particularly with respect to inhibitor titre at <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> start and avoidance of adverse events or interruption of treatment, may also contribute to improve outcomes. Although the economic constraints of the present era significantly affect resources for such a high\u2010cost treatment, the individual cost\u2010utility ratio (bleeding tendency and risk of fatal bleeding, arthropathy and need for orthopaedic surgery, comorbidities, quality of life) should be assessed carefully to determine whether <jats:styled-content style=\"fixed-case\">ITI<\/jats:styled-content> is a suitable option and thus not preclude adults from the opportunity of inhibitor eradication.<\/jats:p>","DOI":"10.1111\/hae.12052","type":"journal-article","created":{"date-parts":[[2012,12,21]],"date-time":"2012-12-21T23:16:43Z","timestamp":1356131803000},"page":"18-23","source":"Crossref","is-referenced-by-count":13,"title":["Management of patients with long\u2010term inhibitors: is immune tolerance an underestimated life\u2010long solution?"],"prefix":"10.1111","volume":"19","author":[{"given":"G.","family":"Di Minno","sequence":"first","affiliation":[{"name":"Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine Federico II University Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Coppola","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine Federico II University Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08263.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0941"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2004.00710.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01518.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2005.01161.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06087.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01296.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01497.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.1995.tb00036.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.3.983.983"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2000.00379.x"},{"key":"e_1_2_7_13_1","first-page":"558","article-title":"Immune tolerance induction with recombinant factor VIII in hemophilia A patients with high responding inhibitors","volume":"91","author":"Rocino A","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_7_14_1","first-page":"1186","article-title":"Immune tolerance in hemophilia with inhibitors: predictors of success","volume":"86","author":"Mariani G","year":"2001","journal-title":"Haematologica"},{"key":"e_1_2_7_15_1","first-page":"45","article-title":"The German registry of immune tolerance treatment in hemophilia \u2013 1999 update","volume":"85","author":"Lenk H","year":"2000","journal-title":"Haematologica"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1612943"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03615.x"},{"issue":"3","key":"e_1_2_7_18_1","first-page":"88","article-title":"How many patients with high\u2010responding inhibitors did\/did not undergo immune tolerance induction in Italy? 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