Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes

for the Joint Outcome Study Group Investigators

Research output: Contribution to journalArticle

Abstract

Introduction: The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained. Aim: In this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS. Methods: We evaluated the influence of FVIII half-life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint-space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations. Results: Prophylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured. Conclusion: In the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half-life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).

Original languageEnglish (US)
JournalHaemophilia
DOIs
StatePublished - Jan 1 2019

Fingerprint

Factor VIII
Hemophilia A
Hemostasis
Joints
Outcome Assessment (Health Care)
Half-Life
Logistic Models
Therapeutics
Bone Cysts
Coagulants
Anticoagulants
Proteins
Regression Analysis
Hemorrhage

Keywords

  • blood coagulation factors
  • global assays
  • haemophilia
  • joints
  • paediatric
  • prophylaxis

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

@article{2f6a9879e4754965a5f9ada021b976c1,
title = "Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes",
abstract = "Introduction: The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained. Aim: In this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS. Methods: We evaluated the influence of FVIII half-life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint-space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations. Results: Prophylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured. Conclusion: In the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half-life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).",
keywords = "blood coagulation factors, global assays, haemophilia, joints, paediatric, prophylaxis",
author = "{for the Joint Outcome Study Group Investigators} and Warren, {Beth Boulden} and Linda Jacobson and Christine Kempton and Buchanan, {George R.} and Michael Recht and Deborah Brown and Cindy Leissinger and Shapiro, {Amy D.} and Abshire, {Thomas C.} and Manco-Johnson, {Marilyn J.} and Brenda Riske and Hacker, {Michele R.} and Ray Kilcoyne and Ingram, {J. David} and Manco-Johnson, {Michael L.} and Sharon Funk and Valentino, {Leonard A.} and Hoots, {W. Keith} and Donna DiMichele and Shirley Bleak and Alan Cohen and Prasad Mathew and Alison Matsunaga and Desiree Medeiros and Diane Nugent and Thomas, {Gregory A.} and Thompson, {Alexis A} and Kevin McRedmond and Soucie, {J. Michael} and Harlan Austin and Evatt, {Bruce L.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/hae.13778",
language = "English (US)",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell",

}

Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes. / for the Joint Outcome Study Group Investigators.

In: Haemophilia, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes

AU - for the Joint Outcome Study Group Investigators

AU - Warren, Beth Boulden

AU - Jacobson, Linda

AU - Kempton, Christine

AU - Buchanan, George R.

AU - Recht, Michael

AU - Brown, Deborah

AU - Leissinger, Cindy

AU - Shapiro, Amy D.

AU - Abshire, Thomas C.

AU - Manco-Johnson, Marilyn J.

AU - Riske, Brenda

AU - Hacker, Michele R.

AU - Kilcoyne, Ray

AU - Ingram, J. David

AU - Manco-Johnson, Michael L.

AU - Funk, Sharon

AU - Valentino, Leonard A.

AU - Hoots, W. Keith

AU - DiMichele, Donna

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 - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained. Aim: In this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS. Methods: We evaluated the influence of FVIII half-life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint-space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations. Results: Prophylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured. Conclusion: In the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half-life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).

AB - Introduction: The Joint Outcome Study (JOS) demonstrated that previously untreated children with severe haemophilia A treated with prophylactic factor VIII (FVIII) concentrate had superior joint outcomes at age 6 years compared to those children treated episodically for bleeding. However, variation in joint outcome within each treatment arm was not well explained. Aim: In this study, we sought to better understand variation in joint outcomes at age 6 years in participants of the JOS. Methods: We evaluated the influence of FVIII half-life, treatment adherence, constitutional coagulant and anticoagulant proteins, and global assays on joint outcomes (number of joint bleeds, total number of bleeds, total MRI score and joint physical exam score). Logistic regression was used to evaluate the association of variables with joint failure status on MRI, defined as presence of subchondral cyst, surface erosion or joint-space narrowing. Each parameter was also correlated with each joint outcome using Spearman correlations. Results: Prophylaxis treatment arm and FVIII trough were each found to reduce risk of joint failure on univariate logistic regression analysis. When controlling for treatment arm, FVIII trough was no longer significant, likely because of the high level of covariation between these variables. We found no consistent correlation between any laboratory assay performed and any joint outcome parameter measured. Conclusion: In the JOS, the effect of prescribed prophylactic FVIII infusions on joint outcome overshadowed the contribution of treatment adherence, FVIII half-life, global assays of coagulation and constitutional coagulation proteins. (ClinicalTrials.gov number, NCT00207597).

KW - blood coagulation factors

KW - global assays

KW - haemophilia

KW - joints

KW - paediatric

KW - prophylaxis

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JF - Haemophilia

SN - 1351-8216

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