title: Intermediate-dose versus high-dose prophylaxis for severe hemophilia: comparing outcome and costs since the 1970s.
abstract: Prophylactic treatment in severe hemophilia is very effective but is limited by cost issues. The implementation of 2 different prophylactic regimens in The Netherlands and Sweden since the 1970s may be considered a natural experiment. We compared the costs and outcomes of Dutch intermediate- and Swedish high-dose prophylactic regimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970 and 1994, using prospective standardized outcome assessment and retrospective collection of cost data. Seventy-eight Dutch and 50 Swedish patients, median age 24 years (range, 14-37 years), were included. Intermediate-dose prophylaxis used less factor concentrate (median: Netherlands, 2100 IU/kg per year [interquartile range (IQR), 1400-2900 IU/kg per year] vs Sweden, 4000 IU/kg per year [IQR, 3000-4900 IU/kg per year]); (P < .01). Clinical outcome was slightly inferior for the intermediate-dose regimen (P < .01) for 5-year bleeding (median, 1.3 [IQR, 0.8-2.7] vs 0 [IQR, 0.0-2.0] joint bleeds/y) and joint health (Haemophilia Joint Health Score >10 of 144 points in 46% vs 11% of participants), although social participation and quality of life were similar. Annual total costs were 66% higher for high-dose prophylaxis (mean, 180 [95% confidence interval, 163 - 196] × US$1000 for Dutch vs 298 [95% confidence interval, 271-325]) × US$1000 for Swedish patients; (P < .01). At group level, the incremental benefits of high-dose prophylaxis appear limited. At the patient level, prophylaxis should be tailored individually, and many patients may do well receiving lower doses of concentrate without compromising safety.
authors.affiliation: Van Creveldkliniek, Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. k.fischer@umcutrecht.nl
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Fischer
authors.forename: Katarina
authors.initials: K
authors.lastname: Steen Carlsson
authors.forename: Pia
authors.initials: P
authors.lastname: Petrini
authors.forename: Margareta
authors.initials: M
authors.lastname: Holmström
authors.forename: Rolf
authors.initials: R
authors.lastname: Ljung
authors.forename: H Marijke
authors.initials: HM
authors.lastname: van den Berg
authors.forename: Erik
authors.initials: E
authors.lastname: Berntorp
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005164:Factor IX / Q000008:administration & dosage*; D005169:Factor VIII / Q000008:administration & dosage*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000191:economics*; D006801:Humans; D007223:Infant; D008297:Male; D009426:Netherlands; D011446:Prospective Studies; D011788:Quality of Life; D012189:Retrospective Studies; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; D005169:Factor VIII; D005164:Factor IX