In the phase 3 B-LONG (Recombinant Factor IX Fc Fusion Protein [rFIXFc] in Subjects With Haemophilia B) study, rFIXFc demonstrated a prolonged half-life compared with recombinant factor IX (rFIX), and safety and efficacy for prophylaxis and treatment of bleeding in subjects with moderately-severe to severe haemophilia B. In this B-LONG sub-analysis, rFIXFc was evaluated for efficacy in subjects requiring major surgery. Dosing was investigator-determined. Assessments included dosing, consumption, bleeding, transfusions and haemostatic response. A population pharmacokinetics model of rFIXFc was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXFc prophylaxis before surgery (range, ~2 weeks-12 months). Investigators/surgeons rated haemostatic responses as excellent (n = 13) or good (n = 1). In most surgeries (85·7%), haemostasis from the pre-surgical dose until the end of surgery was maintained with a single rFIXFc infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation (R2 = 0·9586, P < 0·001) between observed and population pharmacokinetic model-predicted FIX activity suggests surgery did not impact rFIXFc pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXFc was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXFc pharmacokinetics.1681124134Collins, P.W., Moss, J., Knobe, K., Groth, A., Colberg, T., Watson, E., Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX (2012) Journal of Thrombosis and Haemostasis, 10, pp. 2305-2312Diao, L., Li, S., Ludden, T., Gobburu, J., Nestorov, I., Jiang, H., Population Pharmacokinetic Modelling of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Patients with Haemophilia B (2014) Clinical Pharmacokinetics, 53, pp. 467-477Hermans, C., Altisent, C., Batorova, A., Chambost, H., De Moerloose, P., Karafoulidou, A., Klamroth, R., Dolan, G., Replacement therapy for invasive procedures in patients with haemophilia: literature review, European survey and recommendations (2009) Haemophilia, 15, pp. 639-658Klitgaard, T., Nielsen, T.G., Overview of the human pharmacokinetics of recombinant activated factor VII (2008) British Journal of Clinical Pharmacology, 65, pp. 3-11Longo, G., Messori, A., Morfini, M., Baudo, F., Ciavarella, N., Cinotti, S., Filimberti, E., Ferrini, P.R., Evaluation of factor VIII pharmacokinetics in hemophilia-A subjects undergoing surgery and description of a nomogram for dosing calculations (1989) American Journal of Hematology, 30, pp. 140-149(2007), https://www.hemophilia.org/sites/default/files/document/files/masac179.pdf, MASAC Recommendation Concerning Prophylaxis (Regular Administration of Clotting Factor Concentrate to Prevent Bleeding). MASAC Document #179. Accessed 8-19-2013Powell, J.S., Pasi, J., Ragni, M.V., Ozelo, M.C., Valentino, L.A., Mahlangu, J.N., Josephson, N.C., Pierce, G.F., Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B (2013) New England Journal of Medicine, 369, pp. 2313-2323Powell, J., Shapiro, A., Ragni, M., Negrier, C., Windyga, J., Ozelo, M., Pasi, J., Robinson, B., Switching to recombinant factor IX Fc fusion protein prophylaxis results in fewer infusions, decreased factor IX consumption and lower bleeding rates (2014) British Journal of HaematologyPrasad, N., Padmanabhan, V., Mullaji, A., Blood loss in total knee arthroplasty: an analysis of risk factors (2007) International Orthopaedics, 31, pp. 39-44Quon, D.V., Logan, L., Safety and efficacy of plasma-derived coagulation factor IX concentrate (AlphaNine(R) SD) in patients with haemophilia B undergoing surgical intervention: a single institution retrospective analysis (2011) Haemophilia, 17, pp. e196-e201Ragni, M.V., Pasi, K.J., White, G.C., Giangrande, P.L., Courter, S.G., Tubridy, K.L., Use of recombinant factor IX in subjects with haemophilia B undergoing surgery (2002) Haemophilia, 8, pp. 91-97Rudowski, W.J., Scharf, R., Ziemski, J.M., Is major surgery in hemophiliac patients safe? (1987) World Journal of Surgery, 11, pp. 378-386Sommer, J., Buyue, Y., Bardan, S., Peters, R.T., Jiang, H., Kamphaus, G.D., Gray, E., Pierce, G.F., Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity (2014) Thrombosis and Haemostasis, , [Epub ahead of print]Srivastava, A., Brewer, A.K., Mauser-Bunschoten, E.P., Key, N.S., Kitchen, S., Llinas, A., Ludlam, C.A., Street, A., Guidelines for the management of hemophilia (2013) Haemophilia, 19, pp. e1-e47White, G.C., Beebe, A., Nielsen, B., Recombinant factor IX (1997) Thrombosis and Haemostasis, 78, pp. 261-265Windyga, J., Rusen, L., Gruppo, R., O'Brien, A.C., Kelly, P., Roth, D.A., Arkin, S., BDDrFVIII (Moroctocog alfa [AF-CC]) for surgical haemostasis in patients with haemophilia A: results of a pivotal study (2010) Haemophilia, 16, pp. 731-739Windyga, J., Lissitchkov, T., Stasyshyn, O., Mamonov, V., Ghandehari, H., Chapman, M., Fritsch, S., Abbuehl, B.E., Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study (2014) Haemophilia, , [Epub ahead of print]