PO043 | MULTICENTRE REAL‑WORLD EXPERIENCE OF EMICIZUMAB PROPHYLAXIS IN AN ITALIAN COHORT OF 49 CHILDREN WITH SEVERE HEMOPHILIA A - EMIPED STUDY

L. Pieri¹, B. Pollio², P. Giordano³, G. Lassandro⁴, S. Linari¹, R. Pasquino¹, E. Piellucci¹, MC. Di Stefano¹, F. Demartis¹, R. Fjerza¹, G. Castaman¹ | ¹Center for Bleeding Disorders, Careggi University Hospital, Firenze, Italy; ²Center for Inherited Bleeding and Thrombotic Disorders, Transfusion Medicine, "Regina Margherita" Children Hospital, Torino, Italy; ³Department of Interdisciplinary of Medicine, University of Bari 'Aldo Moro', Bari, Italy; ⁴General and Specialised Pediatrics Unit, "Giovanni XXIII" Hospital, University of Bari, Bari, Italy

Background. Emicizumab prophylaxis is approved for people of all ages with hemophilia A (HA) with and without inhibitors. Efficacy and tolerability of emicizumab have been evaluated in children and adolescents in phase III studies and the HAVEN 7 phase IIIb clinical trial evaluating infants is ongoing. However, real-world data on emicizumab use in children and infants are limited.
Aims. We aim to evaluate the clinical impact in transitioning from substitutive therapy/bypassing agents to emicizumab in HA paediatric Italian population.
Methods. Using a retro-prospective medical record chart review, we conducted a self-control analysis of 49 patients less than 18 years of age from Haemophilia Centers of Turin, Florence and Bari, during equivalent periods of 12 months of factor replacement therapy versus emicizumab prophylaxis. The study was approved by the Ethical Committees of the Centers involved. Statistical comparisons between different groups were made using one-way ANOVA at a significance level of 0.05.
Results. We evaluated 49 male patients (pts) affected by severe HA, 9 with inhibitors (PWI) and 40 without inhibitors (PWoI). Among PWI, 6 pts developed inhibitors in the 12 months before emicizumab, 1 pt was in aPCC prophylaxis and 2 on demand treatment with rFVIIa. Among PWoI, 4 (8.7%) were never treated with substitutive therapy, 12 (26%) were treated on demand and 30 (65.3%), including the ones who developed inhibitors, were on different prophylaxis regimens. Standard half-life FVIII concentrate were used by 33/46 pts (71.7%) and extended half-life by 13/46 pts (28.3%). The median age at the initiation of emicizumab was 4.5 years (range: 2 months–17 years). 9 pts were younger than 1 year. Emicizumab was used to initiate prophylaxis in 16 PWoI, including 4 PUPs, with a median age of 1 year, range 2-12 months. The chosen regimen for prophylaxis after the loading phase was 1.5 mg/kg/7days for 23 pts, 3 mg/kg/14days for 21 pts and 6 mg/kg/28 days for 5 pts. No pts discontinued emicizumab in the first 12 months of therapy. Data about FVIII concentrate consumption were available for 14 PWoI: in the 12 months before emicizumab median consumption was 75.500 U, range 0-316.000 U, mean 102.464 ± 104.473 U; in the 12 months after emicizumab median was 750 U per pt, range 0-14.000 U, mean 3.643 ± 5.059 U. 31/49 pts (63.3%) had at least one bleeding episode in the 12 months before emicizumab versus 17/49 pts (28.6%) in the 12 months after emicizumab (p=0.004). 17/49 pts (34.7%) had at least one access to emergency department and 11/49 pts (22.5%) at least one hospitalization due to bleeding episodes and/or trauma in the 12 months before emicizumab versus 9/49 pts (28.6%, p=0.05) and 1/49 pts (2%, p=0.002), respectively, in the 12 months after emicizumab start. 6/49 pts (12%) had at least one target joint in the 12 months before emicizumab versus 0/49 pts in the 12 months after emicizumab (p=0.01).
Conclusions. In this population of pediatric HA pts with and without inhibitors, emicizumab prophylaxis was safe and effective in reducing bleeding episodes, including joint bleeds, resolving all the target joints. Likewise, hospitalization due to bleeds and trauma was significantly reduced. No adverse events requiring emicizumab discontinuation occurred, including the 9 pts younger than 1 year at emicizumab start.