{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:55:20Z","timestamp":1787838920715,"version":"build-2784847793"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T00:00:00Z","timestamp":1467072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["152002004"],"award-info":[{"award-number":["152002004"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Lifelong prophylactic replacement therapy with clotting factor concentrates is recommended for severe haemophilia. The prophylactic dose determines both clinical outcome and treatment cost. In the absence of clinical studies, computer simulation was used to explore lifelong effects and clotting factor consumption for various prophylactic dose levels, and optimize strategies for switching between prophylactic and on\u2010demand treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Methods<\/jats:title><jats:p>Individual patients\u2019 lifetime joint bleeds, radiological arthropathy (Pettersson score, 0\u201378) and consumption were simulated for each treatment strategy. Treatment effectiveness (expressed as % of patients maintaining a lifetime Pettersson score \u226414) and clotting factor consumption were modelled for lifelong prophylaxis at dose levels 1000\u20134500 IU kg<jats:sup>\u22121<\/jats:sup> year<jats:sup>\u22121<\/jats:sup>, for on\u2010demand treatment and for switching strategies. Treatment efficiency (consumption per unit of effectiveness) was used to compare strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to lifelong on\u2010demand treatment, lifelong prophylaxis at 1000 IU kg<jats:sup>\u22121<\/jats:sup> year<jats:sup>\u22121<\/jats:sup> increased effectiveness from 21 to 36%, at an additional consumption of 0.9 \u00d7 10<jats:sup>6<\/jats:sup> IU kg<jats:sup>\u22121<\/jats:sup>. For lifelong prophylaxis, each additional 1000 IU kg<jats:sup>\u22121<\/jats:sup> year<jats:sup>\u22121<\/jats:sup> resulted in a proportional increase in consumption by \u00b15 \u00d7 10<jats:sup>6<\/jats:sup> IU kg<jats:sup>\u22121<\/jats:sup> but a less than proportional reduction in arthropathy by \u00b150%; consequently, increasing consumption progressively diminished treatment efficiency. Switching strategies slightly reduce effectiveness and consumption. Optimum switching criteria were similar across prophylactic dose levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>According to the simulation model, low\u2010dose prophylaxis (1000 IU kg<jats:sup>\u22121<\/jats:sup> year<jats:sup>\u22121<\/jats:sup>) improved outcome at a limited increase in consumption compared to on\u2010demand treatment. Increasing prophylactic dose further improved health outcomes, but at decreasing efficiency. Optimal prophylactic dose should therefore be selected balancing acceptable health impact and available budget.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13019","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T15:58:47Z","timestamp":1467215927000},"source":"Crossref","is-referenced-by-count":11,"title":["Modelling lifelong effects of different prophylactic treatment strategies for severe haemophilia A"],"prefix":"10.1111","volume":"22","author":[{"given":"K.","family":"Fischer","sequence":"first","affiliation":[{"name":"Julius Center for Health Sciences and Primary care University Medical Center Utrecht Utrecht The Netherlands"},{"name":"Van Creveldkliniek University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary care University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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