PSY14 - A Comparison of Prophylactic Versus On-Demand Treatment Regimens of Coagulation Factor VIII for Bleeding and Joint Outcomes in Hemophilia a Patients Without Inhibitors: A Systematic Review and Meta-Analysis

Abstract

To conduct a systematic literature review and meta-analysis to examine differences in bleeding and joint outcomes between prophylaxis and on-demand treatment regimens of factor VIII concentrates in moderate to severe hemophilia A patients without inhibitors. A comprehensive search of the PubMed, EMBASE, and Cochrane databases was conducted through August 2017 for studies that compared bleeding and/or joint outcomes between patients using prophylaxis and on-demand regimens of factor VIII concentrates for hemophilia A without inhibitors. Qualitative synthesis of all included studies was performed. Pooled effect estimates were calculated using fixed and random effects model for studies that reported mean annualized bleeding rates (ABRs) for all bleeds and joint bleeds. Uncertainty was evaluated by conducting subgroup analyses. A total of 12 studies were identified for a qualitative review, of which 6 were eligible for meta-analysis. All studies reported varying measures of all bleeds and joint bleeds outcomes. Spontaneous and trauma bleeding outcomes were reported by 6 and 5 studies respectively. Joint health and damage outcomes were reported by 6 studies. Median ABRs in the on-demand groups were higher than the prophylaxis groups by 67-100% for all bleeds and 78-100% for joint bleeds. Pooled estimates for the standardized differences in mean (SDM) ABRs for all bleeds significantly favored prophylaxis compared to on-demand therapy (SDM = -2.61; 95% CI = -1.55, -3.67). Subgroup analyses showed that randomization, follow-up period greater than 1 year and specified age group were effect modifiers (p<0.001) significantly reducing heterogeneity in pooled effect estimates. Prophylaxis regimen was found to have significantly better bleeding outcomes than on-demand regimen in spite of heterogeneity in study design and populations. Joint outcomes were not reported uniformly but were found to be better for patients on the prophylaxis regimen than on-demand regimen.