Efficacy, safety and cost of emicizumab prophylaxis in haemophilia A patients with inhibitors: A nationwide observational study in Taiwan.

INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis. METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors. RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years. CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

Does Hemophilia Increase Risk of Adverse Outcomes Following Total Hip and Knee Arthroplasty? A Propensity Score-Matched Analysis of a Nationwide, Population-Based Study.

BACKGROUND: End-stage hemophilic arthropathy is the result of recurrent joint hemarthrosis. Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) can reduce severe joint pain and improve functional activity, controversy remains regarding outcomes after THA and TKA among patients with hemophilia. This study evaluated the risk of adverse outcomes of hemophilia patients who underwent THA and TKA. METHODS: This retrospective cohort study was conducted using data from the National Health Insurance Research Database. Patients who had hemophilia and underwent THA and TKA between 2000 and 2015 were identified. A total of 121 patients with hemophilia and 194,026 patients without hemophilia were included. Through propensity score matching, patients with hemophilia were matched at a 1:4 ratio to patients without hemophilia. Multivariable regression analysis was used to control for confounding variables and compare the risk of postoperative complications and mortality, differences in length of stay, and cost of care for the hospital. RESULTS: After propensity score matching and multivariate regression analysis, the adjusted hazard ratio of postoperative transfusion for hemophilia patients was 5.262 (95% confidence interval [CI] = 3.044-26.565, P < .001) in THA group and 6.279 (95% CI = 3.246-28.903, P < .001) in TKA group, when compared with the control group. Patients with hemophilia had longer length of hospital stay (THA group: 95% CI, 1.541-2.669, P < .001; TKA group: 95% CI, 1.568-2.786; P < .001) and higher total hospital charges (THA group: 95% CI, 3.518-8.293, P < .001; TKA group: 95% CI, 3.584-8.842; P < .001) compared to patients without hemophilia. Hemophiliacs had a higher yet nonsignificant 1-year infection rate (8.11% vs 3.38%, P = .206) in the THA group. There were no differences between the rates of 30-day and 90-day complications, 1-year infection, reoperation and mortality between the hemophilia and nonhemophilia groups. CONCLUSION: Hemophilia patients have higher rates of postoperative transfusion, hospital costs, and increased length of stay. There is an appreciable clinical difference in 1-year infection rates following THA but our analysis was limited by the small sample size. Other postoperative complications and mortality rates were comparable. Patients with hemophilia should be counseled that infection rate maybe as high as 8% following THA. Further investigation is needed to develop prophylactic and effective methods to decrease the rates of transfusions and associated adverse outcomes in hemophilia patients undergoing THA and TKA.