PRO8 PROPHYLAXIS IN HEMOPHILIC PATIENTS WITH INHIBITORS: IT IS POSSIBLE TO COMPARE PEARS WITH APPLES?

Abstract

First RCT of prophylaxis in hemophilia with inhibitors was published by Konkle (2007) and its objective was to evaluate rFVIIa prophylaxis efficacy phylaxis with rFVIIa in patients with high drug demand. Emicizumab was recently launched for a similar use (Oldenburg, 2017), the aim of this study is to identify population features of both RCTs to establish if it is possible to make an indirect comparison between both strategies. A review of population features of pivotal RCTs of rFVIIa and emicizumab was made to identify clinical characteristics of disease in each population. It is important to identify these features because the results depend not only on the effectiveness of every medication but also on frequency of bleeding of patients before receiving the medication. Patients in rFVIIa RCT had severe hemophilia with inhibitors and least four bleeding episodes one month before the trial. Patients were excluded if they had < 12 bleeding episodes last three months. Bleding frequency median was 6,3 (IQR= 4,8-8,5) and maximum value was 9,2. Patients in emicizumab RCT had severe and moderate hemophilia with inhibitors. Bleding frequency median was 1,0 (IQR= 0,55-1,7), minimum value was 0 and maximum value was 2,9. There were two outlier values: 3,7 and 4,8. In Konkle' RCT, patients received rFVIIa for 3 months and 16,44 bleeding episodes were avoided as average, for six months (including a 3 months post-prophylaxis period). In Oldenburg' RCT, patients received emicizumab for 6 months and avoided 6,18 bleeding episodes as average, for six months (there was not a post-prophylaxis period). Patients who do not stop bleeding with emicizumab, had to receive rFVIIa to stop the bleeding. Bleeding episodes frequency during pre-prophylaxis period of patients included in rFVIIa RCT was almost 5 times higher than that of patients included in emicizumab RCT, those patients are not comparable between them.