Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia

Marilyn J. Manco-Johnson, Thomas C. Abshire, Amy D. Shapiro, Brenda Riske, Michele R. Hacker, Ray Kilcoyne, J. David Ingram, Michael L. Manco-Johnson, Sharon Funk, Linda Jacobson, Leonard A. Valentino, W. Keith Hoots, George R. Buchanan, Donna Dimichele, Michael Recht, Deborah Brown, Cindy Leissinger, Shirley Bleak, Alan Cohen, Prasad MathewAlison Matsunaga, Desiree Medeiros, Diane Nugent, Gregory A. Thomas, Alexis A. Thompson, Kevin McRedmond, J. Michael Soucie, Harlan Austin, Bruce L. Evatt

Research output: Contribution to journalArticle

1116 Citations (Scopus)

Abstract

BACKGROUND: Effective ways to prevent arthropathy in severe hemophilia are unknown. METHODS: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). RESULTS: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. CONCLUSIONS: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalNew England Journal of Medicine
Volume357
Issue number6
DOIs
StatePublished - Aug 9 2007

Fingerprint

Joint Diseases
Hemophilia A
Joints
Factor VIII
Group Psychotherapy
Hemorrhage
Magnetic Resonance Imaging
Therapeutics
Elbow Joint
Ankle Joint
Knee Joint
Radiography
Cartilage
Appointments and Schedules
Hospitalization
Catheters
Body Weight
Confidence Intervals
Bone and Bones
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Manco-Johnson, M. J., Abshire, T. C., Shapiro, A. D., Riske, B., Hacker, M. R., Kilcoyne, R., ... Evatt, B. L. (2007). Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. New England Journal of Medicine, 357(6), 535-544. https://doi.org/10.1056/NEJMoa067659

Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. / Manco-Johnson, Marilyn J.; Abshire, Thomas C.; Shapiro, Amy D.; Riske, Brenda; Hacker, Michele R.; Kilcoyne, Ray; Ingram, J. David; Manco-Johnson, Michael L.; Funk, Sharon; Jacobson, Linda; Valentino, Leonard A.; Hoots, W. Keith; Buchanan, George R.; Dimichele, Donna; Recht, Michael; Brown, Deborah; Leissinger, Cindy; Bleak, Shirley; Cohen, Alan; Mathew, Prasad; Matsunaga, Alison; Medeiros, Desiree; Nugent, Diane; Thomas, Gregory A.; Thompson, Alexis A.; McRedmond, Kevin; Soucie, J. Michael; Austin, Harlan; Evatt, Bruce L.

In: New England Journal of Medicine, Vol. 357, No. 6, 09.08.2007, p. 535-544.

Research output: Contribution to journalArticle

Manco-Johnson, MJ, Abshire, TC, Shapiro, AD, Riske, B, Hacker, MR, Kilcoyne, R, Ingram, JD, Manco-Johnson, ML, Funk, S, Jacobson, L, Valentino, LA, Hoots, WK, Buchanan, GR, Dimichele, D, Recht, M, Brown, D, Leissinger, C, Bleak, S, Cohen, A, Mathew, P, Matsunaga, A, Medeiros, D, Nugent, D, Thomas, GA, Thompson, AA, McRedmond, K, Soucie, JM, Austin, H & Evatt, BL 2007, 'Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia', New England Journal of Medicine, vol. 357, no. 6, pp. 535-544. https://doi.org/10.1056/NEJMoa067659
Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. New England Journal of Medicine. 2007 Aug 9;357(6):535-544. https://doi.org/10.1056/NEJMoa067659
Manco-Johnson, Marilyn J. ; Abshire, Thomas C. ; Shapiro, Amy D. ; Riske, Brenda ; Hacker, Michele R. ; Kilcoyne, Ray ; Ingram, J. David ; Manco-Johnson, Michael L. ; Funk, Sharon ; Jacobson, Linda ; Valentino, Leonard A. ; Hoots, W. Keith ; Buchanan, George R. ; Dimichele, Donna ; Recht, Michael ; Brown, Deborah ; Leissinger, Cindy ; Bleak, Shirley ; Cohen, Alan ; Mathew, Prasad ; Matsunaga, Alison ; Medeiros, Desiree ; Nugent, Diane ; Thomas, Gregory A. ; Thompson, Alexis A. ; McRedmond, Kevin ; Soucie, J. Michael ; Austin, Harlan ; Evatt, Bruce L. / Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. In: New England Journal of Medicine. 2007 ; Vol. 357, No. 6. pp. 535-544.
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abstract = "BACKGROUND: Effective ways to prevent arthropathy in severe hemophilia are unknown. METHODS: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). RESULTS: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93{\%} of those in the prophylaxis group and 55{\%} of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95{\%} confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. CONCLUSIONS: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)",
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T1 - Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia

AU - Manco-Johnson, Marilyn J.

AU - Abshire, Thomas C.

AU - Shapiro, Amy D.

AU - Riske, Brenda

AU - Hacker, Michele R.

AU - Kilcoyne, Ray

AU - Ingram, J. David

AU - Manco-Johnson, Michael L.

AU - Funk, Sharon

AU - Jacobson, Linda

AU - Valentino, Leonard A.

AU - Hoots, W. Keith

AU - Buchanan, George R.

AU - Dimichele, Donna

AU - Recht, Michael

AU - Brown, Deborah

AU - Leissinger, Cindy

AU - Bleak, Shirley

AU - Cohen, Alan

AU - Mathew, Prasad

AU - Matsunaga, Alison

AU - Medeiros, Desiree

AU - Nugent, Diane

AU - Thomas, Gregory A.

AU - Thompson, Alexis A.

AU - McRedmond, Kevin

AU - Soucie, J. Michael

AU - Austin, Harlan

AU - Evatt, Bruce L.

PY - 2007/8/9

Y1 - 2007/8/9

N2 - BACKGROUND: Effective ways to prevent arthropathy in severe hemophilia are unknown. METHODS: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). RESULTS: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. CONCLUSIONS: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)

AB - BACKGROUND: Effective ways to prevent arthropathy in severe hemophilia are unknown. METHODS: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). RESULTS: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P = 0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. CONCLUSIONS: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597.)

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