Glaivy Batsuli1, Karen L Zimowski1, Kelly Tickle2, Shannon L Meeks1, Robert F Sidonio1. 1. Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Department of Pediatrics, Emory University, Atlanta, Georgia. 2. Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, Georgia.
Abstract
INTRODUCTION: The formation of neutralizing antifactor VIII (fVIII) antibodies, called inhibitors, is the most common complication in modern haemophilia A care. Novel non-factor replacement therapies, such as emicizumab, have sought to address the limitations of bypassing agents for bleeding management in patients with inhibitors. However, immune tolerance induction (ITI) remains the primary method for eradicating inhibitors and restoring the hemostatic response to fVIII. AIM: The aim of this study was to review a case series of paediatric patients with haemophilia A and inhibitors who have received ITI for inhibitor eradication concomitantly with emicizumab prophylaxis for bleeding prevention. METHODS: Single institution retrospective chart review of paediatric patients with severe haemophilia A receiving ITI and emicizumab. RESULTS: Seven patients were included in this cohort. Six patients used three different recombinant fVIII products at 100 IU/kg three times per week, and one patient used a plasma-derived fVIII product at an initial dose of 50 IU/kg three times per week. Three patients achieved a negative inhibitor titre <0.6 Chromogenic Bethesda Units per mL (CBU/mL), and two patients achieved a normal fVIII recovery ≥66%. There were nine bleeding events in four patients, but no thrombotic events. All patients remained on ITI and emicizumab. CONCLUSION: Immune tolerance induction while on emicizumab prophylaxis is a feasible approach in paediatric haemophilia A patients with inhibitors. This is the first report of the concomitant use of ITI in patients receiving emicizumab prophylaxis described as the 'Atlanta Protocol'.
INTRODUCTION: The formation of neutralizing antifactor VIII (fVIII) antibodies, called inhibitors, is the most common complication in modern haemophilia A care. Novel non-factor replacement therapies, such as emicizumab, have sought to address the limitations of bypassing agents for bleeding management in patients with inhibitors. However, immune tolerance induction (ITI) remains the primary method for eradicating inhibitors and restoring the hemostatic response to fVIII. AIM: The aim of this study was to review a case series of paediatric patients with haemophilia A and inhibitors who have received ITI for inhibitor eradication concomitantly with emicizumab prophylaxis for bleeding prevention. METHODS: Single institution retrospective chart review of paediatric patients with severe haemophilia A receiving ITI and emicizumab. RESULTS: Seven patients were included in this cohort. Six patients used three different recombinant fVIII products at 100 IU/kg three times per week, and one patient used a plasma-derived fVIII product at an initial dose of 50 IU/kg three times per week. Three patients achieved a negative inhibitor titre <0.6 Chromogenic Bethesda Units per mL (CBU/mL), and two patients achieved a normal fVIII recovery ≥66%. There were nine bleeding events in four patients, but no thrombotic events. All patients remained on ITI and emicizumab. CONCLUSION: Immune tolerance induction while on emicizumab prophylaxis is a feasible approach in paediatric haemophilia Apatients with inhibitors. This is the first report of the concomitant use of ITI in patients receiving emicizumab prophylaxis described as the 'Atlanta Protocol'.
Authors: Carmen Escuriola Ettingshausen; Vladimír Vdovin; Nadezhda Zozulya; Pavel Svirin; Tatiana Andreeva; Majda Benedik-Dolničar; Victor Jiménez-Yuste; Lidija Kitanovski; Silva Zupancic-Šalek; Anna Pavlova; Angelika Bátorová; Cesar Montaño Mejía; Gulnara Abdilova; Sigurd Knaub; Martina Jansen; Shannely Lowndes; Larisa Belyanskaya; Olaf Walter; Johannes Oldenburg Journal: TH Open Date: 2022-05-26
Authors: C Hermans; P L F Giangrande; B O'Mahony; P de Kleijn; M Bedford; A Batorova; J Blatný; K Jansone Journal: Orphanet J Rare Dis Date: 2020-08-24 Impact factor: 4.123