Introduction: Emicizumab is a recombinant humanized bispecific antibody that bridges factor IXa and factor X to mimic the cofactor function of factor VIII. It is approved to prevent bleeding in patients with haemophilia A (HA). Outside of clinical trials, there is limited data on outcomes of patients treated with emicizumab, particularly in children without inhibitors. Aim: To report our experience treating patients with emicizumab, including (a) bleeding rates pre and postemicizumab, (b) peri-procedural management and outcomes and (c) serious drug-related adverse events. Methods: Multicentre observational study in patients with HA who started emicizumab prior to 15 May 2019. Data collection continued until 15 October 2019 and included demographics, disease history, bleeding events, invasive procedures, thrombotic events and death. Annualized bleeding rates (ABR) prior to emicizumab were compared to postemicizumab. Results: Ninety-three patients (including three females) met inclusion criteria, 19 with an active inhibitor. Median age was 8.6 years; patients <12 years without inhibitors (n = 49) accounted for the majority. ABR dropped from 4.4 (inhibitors) and 1.6 (non-inhibitors) to 0.4 (both groups) on emicizumab, P = .0012 and .0025, respectively. There were 28 minor (21 port removals) and two major procedures. Three patients received 1-2 doses of unplanned factor postoperatively to treat minor bleeding events. No patient discontinued therapy, and there were no thrombotic events or deaths.
Introduction Emicizumab is a recombinant humanized monoclonal antibody that bridges factor IXa and Factor X and is administered via subcutaneous injection. It provides protection against bleeding in patients with hemophilia A (HA) with and without inhibitors of all ages. Since licensure, the use of emicizumab has increased across hemophilia treatment centers (HTCs). Management of patients on this drug who require procedures has not been well established. The objective of this study was to report peri-procedural hemostasis management as well as bleeding and thrombotic outcomes in a heterogenous group of patients with HA on emicizumab requiring interventional procedures. Methods We conducted a multi-center observational study at 3 federally funded Hemophilia Treatment Centers: Children's Hospital of Philadelphia, Virginia Commonwealth University and Children's National Health System. Inclusion criteria included patients with HA initiated on emicizumab prior to May 15th 2019 that underwent a surgical, dental or interventional procedure prior to July 15, 2019. Data extraction included: demographics, diagnosis, inhibitor, emicizumab dosing data, surgery type, factor used during surgery, and bleeding or thrombotic complications during or after surgery. Results There were a total of 19 procedures in 19 subjects during the study period. 18 were male and all had severe HA. Age at initiation of emicizumab in this cohort ranged from 5 weeks to 27 years; median 5.7 (IQR) yrs. There were 6 patients with an active inhibitor at the time of emicizumab initiation. All patients received emicizumab 3.0 mg/kg weekly x 4 loading doses, followed by either weekly (8), every other week (10), or monthly (1) dosing. There were 18 minor procedures during the study period (14 port removals and one of each of the following: PE tube removal, laparoscopic inguinal hernia repair, arthroscopy, and dental extraction) and one major procedure (intracranial ventricular shunt revision )(Table 1). Of the 14 port removals, 5 patients (1 with inhibitor) did not receive pre-procedure factor replacement; the other 7 received rVIIa or factor VIII pre-procedure and 2 of these patients received a subsequent dose as part of their plan. Three of the 14 patients that underwent port removal (one with inhibitor) were noted to have swelling and hematoma at the surgical site 1-2 days post-op and received 1-2 doses of subsequent factor to treat these bleeding events; only one of these patients did not receive pre-procedure factor. The patient who underwent major surgery received multiple doses of FVIII (to keep FVIII levels >50% x 1 week) and did not have bleeding complications. There were no thrombotic complications. Conclusions In general, the 19 patients with HA who required procedures while on emicizumab did well. Port removal was the most common procedure, which was not surprising given the transition from intravenous to subcutaneous prophylaxis. There was variation in practice, particularly in regard to the need for clotting factor prior to port removal. Most patients did well with 0-1 treatments prior to minor procedures, and no additional replacement. Although 3 of the 14 patients required 1-2 unplanned infusions of clotting factor post port removal, there was no clear relationship between pre-procedure factor replacement and post-procedure port hematoma. This observational study provides useful information for providers who manage patients with HA on emicizumab, although larger studies are clearly needed to help determine best practice. Disclosures Guelcher: Takeda: Other: Advisory Board; Octapharma: Other: Advisory Board; Genetech: Other: Advisory Board; NovoNordisk: Other: Advisory Board. Butler:Hema-Biologics: Consultancy; pfizer: Other: Advisory board; genetech: Other: Advisory board. Guerrera:Bioverativ: Consultancy; Novo Nordisk: Consultancy; Pfizer: Other: Advisory Board; Bayer: Other: Advisory Board; Shire: Other: Advisory Board; Kendrion: Other: Advisory Board; Genetech: Other: Advisory Board. Raffini:Roche: Other: Advisory Board; CSL Behring: Other: Advisory Board; Bayer: Other: Advisory Board.
Introduction Emicizumab is a recombinant humanized monoclonal antibody that bridges factor IXa and Factor Xa and is administered via subcutaneous injection. After initial FDA approval for patients with hemophilia A (HA) and inhibitors, it was approved in October 2018 for prophylaxis in patients with HA without inhibitors of all ages. In clinical trials of subjects without inhibitors, emicizumab was studied only in those >12 years of age. The primary objective of this study was to report our "real-world", post-licensure experience with emicizumab across a more heterogenous patient population, comparing annualized bleeding rates prior to and after initiating emicizumab. Secondary objectives included evaluating for serious adverse events including death, thrombosis or drug discontinuation. Methods We conducted a multi-center observational study at 3 federally funded Hemophilia Treatment Centers: Children's Hospital of Philadelphia, Virginia Commonwealth University and Children's National Health System. Inclusion criteria included patients with HA initiated on emicizumab prior to May 15th 2019. Data extraction included: demographics, diagnosis, prior HA history (inhibitor, prophylaxis treatment regimen), emicizumab dosing data, bleeding events (all bleeds, treated bleeds, joint bleeds, traumatic bleeds) and thrombotic events from the 6 months prior to emicizumab until July 15th 2019. Annualized bleeding rates (ABR) were calculated to account for variable follow up. Wilcoxon Sign-Rank Difference Test was used to test the difference in number of bleeds and McNemar's test was used to test the difference in proportions of patients with ABR=0. Results Ninety-two patients met inclusion criteria: 89 male and 89 with severe HA (3 moderate HA) (Table 1). Age at initiation of emicizumab ranged from 5 weeks to 55 years; median 8.6 yrs (IQR 4.8-13.5 yrs). Nineteen patients had an active inhibitor at the time of starting emicizumab; the remaining 73 did not have an inhibitor, and most (86%) were on prophylaxis prior to emicizumab. Sixty-two patients were < 12 years of age (13 with inhibitors). Median duration of emicizumab therapy was 48 weeks (inhibitors) and 22 weeks (non-inhibitors), with a total follow up of 53.3 patient years. In patients with inhibitors, the ABR (treated bleeds) prior to emicizumab was 6.2 events (95% CI, 0.98 to 11.4) compared to 0.3 events (95% CI, 0 to 0.73) on emicizumab, p=0.002. In subjects without inhibitors, the ABR prior to emicizumab was 1.8 events (95% CI, 0.66 to 2.96) compared to 0.22 events (95% CI, 0.05 to 0.39) on emicizumab, p<0.001. Additional data on bleeding events is provided in Table 1. The proportion of patients with ABR=0 increased in both inhibitor (from 46% to 74%, p=0.06) and non-inhibitor subjects (from 60 to 78%, p=0.015). All patients received 1.5 mg/kg weekly x 4 loading doses, followed by either weekly (27%), every other week (70%), or monthly (3%) dosing; patients with inhibitors were more likely to receive weekly dosing. No patients who initiated emicizumab discontinued the drug or developed a neutralizing antibody to FVIII or emicizumab, although patients have not been consistently screened for these antibodies. No thrombotic or thrombotic microangiopathy events or death have occurred. Conclusions Our favorable clinical experience with emicizumab post-licensure in patients with HA is similar to that reported in the clinical trials. Although excluded from the clinical trials, patients with HA without inhibitors < 12 years accounted for the majority (67%) of our cohort. As anticipated, these younger patients appear to experience the same benefit as patients > 12. No serious drug-related adverse events were reported, although the overall study period is relatively short. Ongoing follow up of these patients, and others, will be important to assess the ongoing safety and efficacy profile of this novel therapy. Updated data on this cohort will be presented at the ASH meeting Disclosures Guelcher: NovoNordisk: Other: Advisory Board; Octapharma: Other: Advisory Board; Takeda: Other: Advisory Board; Genetech: Other: Advisory Board. Butler:pfizer: Other: Advisory board; Hema-Biologics: Consultancy; genetech: Other: Advisory board. Guerrera:Genetech: Other: Advisory Board; Kendrion: Other: Advisory Board; Shire: Other: Advisory Board; Bayer: Other: Advisory Board; Bioverativ: Consultancy; Pfizer: Other: Advisory Board; Novo Nordisk: Consultancy. Raffini:Roche: Other: Advisory Board; Bayer: Other: Advisory Board; CSL Behring: Other: Advisory Board.
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