Presentation Details
| Hemostatic outcome of surgical procedures in patients with hemophilia receiving concizumab prophylaxis: data from the phase 3 explorer7 and explorer8 trials Matthew Evans1, Anthony K.C.Chan2, Chris Barnes3, Mary Mathias4, Silvia Linari5, Francisco-José López-Jaime6, Lone Hvitfeldt Poulsen7, Julien Bovet8, Jan Odgaard-Jensen8, Tadashi Matsushita9, Emily K.Waters10. 1Penn State Health Milton S.Hershey Medical Center, Hershey, PA, USA.2McMaster Children’s Hospital, McMaster Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada.3Royal Children’s Hospital Melbourne, Victoria, Australia.4Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.5Center for Bleeding Disorders and Coagulation, Department of Oncology, Careggi University Hospital, Florence, Italy.6Hospital Regional Universitario de Málaga, Málaga, Spain.7The Haemophilia Centre, Department of Haematology, Aarhus University Hospital, Aarhus, Denmark.8Novo Nordisk A/S, Søborg, Denmark.9Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.10Novo Nordisk Inc., Plainsboro, NJ, USA |
Abstract
Background: Concizumab, a monoclonal antibody targeting the tissue factor pathway inhibitor, has been developed for once-daily subcutaneous prophylactic treatment of hemophilia A (HA) and hemophilia B (HB) with and without inhibitors. The safety and efficacy of concizumab prophylaxis was investigated in the phase 3 explorer7 (NCT04083781; patients with hemophilia A or B with inhibitors [HAwI/HBwI]) and explorer8 (NCT04082429; patients with HA or HB without inhibitors) trials. Objectives: To detail the hemostatic outcomes related to minor surgical procedures performed on patients with HA and HB with and without inhibitors who received concizumab prophylaxis in the explorer7 and explorer8 trials. Methods: Based on their prior treatment regimen, patients enrolled in explorer7 and explorer8 were exposed to no prophylaxis (arm 1) or concizumab prophylaxis (arms 2-4). After completing the main part of the trials, patients from any arm could continue in the trial extension, during which they received concizumab prophylaxis. Ethics committee approvals and informed consent were obtained where appropriate. Minor surgical procedures were permitted during both trials; these were defined as any invasive operative procedure in which only the skin, mucus membranes, or superficial connective tissue were manipulated. Planned major surgery was not permitted, and a concizumab pause was recommended for acute major surgery cases. Local or topical use of antifibrinolytics was permitted during surgical procedures, and patients undergoing minor surgical procedures continued to receive concizumab prophylaxis perioperatively with no change in dosage. Results: In total, 278 patients in the explorer7 and explorer8 trials received concizumab prophylaxis. Of these, 30 patients underwent a minor surgical procedure, including 6 adolescents (20.0%), aged 12 to 17 years, and 24 adults (80.0%), aged 18 to 64 years. Within this group, 9 (30.0%) had HA, 10 (33.3%) had HB, 7 (23.3%) had HAwI, and 4 (13.3%) had HBwI. The most common minor surgeries were dental procedures (n=24); other minor surgeries included port removal, colonoscopy, arthrodesis, and urethral augmentation. Fifteen bleeding episodes were reported in 14 of 38 minor surgical procedures; 8 episodes required hemostatic intervention. Fourteen of the 15 bleeding episodes were classified as mild or moderate. The median duration of minor surgery-related bleeding was 2 days, and the mean (SD) number of factor product injections required to treat these bleeds was 1.5 (0.8). Of the 14 reported bleeds, 12 were related to dental surgical procedures, 1 was related to port removal, and 1 was related to venesection. Conclusions: Approximately 11% of patients who received concizumab treatment during the explorer7 and explorer8 trials underwent minor surgical procedures. Most minor surgeries were dental procedures, and most surgery-related bleeding episodes were characterized as mild or moderate. These data indicate that minor surgeries can be conducted safely during treatment with concizumab.
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