Factor VIII prophylaxis effects outweigh other hemostasis contributors in predicting severe haemophilia A joint outcomes
Beth Boulden Warren, Linda Jacobson, Christine Kempton, George R Buchanan, Michael Recht, Deborah Brown, Cindy Leissinger, Amy D Shapiro, Thomas C Abshire, Marilyn J Manco-Johnson, Joint Outcome Study Group Investigators, Brenda Riske, Michele R Hacker, Ray Kilcoyne, J David Ingram, Michael L Manco-Johnson, Sharon Funk, Leonard A Valentino, W Keith Hoots, Donna DiMichele, Shirley Bleak, Alan Cohen, Prasad Mathew, Alison Matsunaga, Desiree Medeiros, Diane Nugent, Gregory A Thomas, Alexis A Thompson, Kevin McRedmond, J Michael Soucie, Harlan Austin, Bruce L Evatt, Beth Boulden Warren, Linda Jacobson, Christine Kempton, George R Buchanan, Michael Recht, Deborah Brown, Cindy Leissinger, Amy D Shapiro, Thomas C Abshire, Marilyn J Manco-Johnson, Joint Outcome Study Group Investigators, Brenda Riske, Michele R Hacker, Ray Kilcoyne, J David Ingram, Michael L Manco-Johnson, Sharon Funk, Leonard A Valentino, W Keith Hoots, Donna DiMichele, Shirley Bleak, Alan Cohen, Prasad Mathew, Alison Matsunaga, Desiree Medeiros, Diane Nugent, Gregory A Thomas, Alexis A Thompson, Kevin McRedmond, J Michael Soucie, Harlan Austin, Bruce L Evatt
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.
Conflict of interest statement
Conflicts of Interest
The remaining authors have no conflicts of interest to declare.
© 2019 John Wiley & Sons Ltd.
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Source: PubMed