PO24 | Emicizumab prophylaxis and bleeding outcomes: a single center clinical experience

A. Taglietti¹, S. Ligia¹, F. Paoletti¹, R. Mormile¹, E. Baldacci², A. Chistolini¹, C. Santoro^1,2 | ¹Hematology, Department of Translational and Precision Medicine, Sapienza University of Roma; ²Hematology, Azienda Ospedaliera Universitaria Policlinico Umberto I, Roma, Italy

Background and Aims: Emicizumab for hemophilia A (HA) has been increasingly employed in clinical practice. The aim is describing our real-world experience and clinical outcomes in severe HA patients (pts).

Methods: Retrospective, single-center study including severe HA pts, with/without inhibitors, with 6-month minimum follow-up (FU) since emicizumab start. Clinical data were collected from clinical charts and all participants signed an informed consent form.

Results: We enrolled 29 severe HA pts who switched to emicizumab prophylaxis (EP). The only adverse event we recorded was a local skin reaction in 1 pt after his 1st emicizumab dose. Non-Inhibitor patients: 24 pts (82.8%), whose median age at switch was 14.1 years (7.43-38.33; min 0.65-max 55.33) and median FU is 16.97 months (9.6-27.2). Before EP, 3 (12.5%) were therapy naive, 2 (8.3%) treated on-demand, 19 (79.2%) were on recombinant factor VIII (rFVIII) prophylaxis. The main reasons for switching were achieving better bleeding control, avoiding intravenous infusion, and improving compliance. During EP, 1 pediatric pt, who had previously received few rFVIII infusions, developed an inhibitor following a traumatic injury that required rFVIII treatment. Patients with inhibitors (PwI): 5 pts (17.2%), whose median age at switch was 58.1 years (37.95-67.7) and median FU is 51.7 months (37.63- 73.75). All were treated with on-demand recombinant activated factor VII (rFVIIa). Procedures: during EP, 11 procedures were performed in 7 (13.8%) pts (4 PwI, 3 non-inhibitor): 4 major surgeries, 3 minor ones, 4 dental extractions. Major surgeries were managed with rFVIII/FVIIa, yet 1 PwI presented postoperative bleeding complications (melena after pancreatic biopsy) that required transfusions and large amounts of rFVIIa. Bleedings: During the 2 years prior to switch, 25 (85.2%) pts experienced at least one bleeding episode (5 PwI and 20 non-inhibitor). Comparing the mean annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR), PwI had significantly higher rates (p=0.0116 and p=0.0092). During EP, 14/29 (48.3%) pts never experienced a bleeding episode. 11 non-inhibitor pts experienced 19 mild-moderate bleeds: 17 traumatic and 2 spontaneous hematuria (same pt), all managed with rFVIII therapy. 4 PwI experienced a total of 5 mild-moderate bleeds: 4 traumatic (managed with rFVIIa) and 1 small spontaneous hematoma. Comparing pre-vs-post emicizumab ABR and AJBR, we observed a reduction by 63.78% (p=0.0114) and 56.52% (p=0.17) in the non-inhibitor group and a reduction by 96.17% (p=0.0079) and 98.57% (p=0.0476) in PwI. No significant difference was found in ABR and AJBR between PwI and non-inhibitor during EP (p=0.69 and p=0.63, respectively). During EP, ABR and AJBR did not differ between pediatric (age<12 years, 11 pts) and adult pts (age>12 years, 18 pts).

Conclusions: Despite our small cohort, we confirmed emicizumab efficacy and safety in severe HA pts with/without inhibitor. The different age and FU between the pt groups depend on timelines of regulatory indications for prescription. Only 2 pts had mild spontaneous bleeds and traumas were all easily managed. 1 PwI had severe bleeding after a high-risk procedure, despite additional rFVIIa. We found no significant differences in bleeding rates between pt groups during EP. We believe that the smaller AJBR reduction in the non-inhibitor group may be explained by a more confident approach to physical activity by pediatric pts.