A contemporary look at FVIII inhibitor development: still a great influence on the evolution of hemophilia therapies

References

• Peyvandi F, Mannucci PM, Garagiola I, et al. A randomized trial of factor VIII and neutralizing antibodies in hemophilia A. N Engl J Med. 2016;374(21):2054–2064.
   PubMed Web of Science ®Google Scholar
• Rosner F. Moses maimonides (1135 to 1204). Ann Intern Med. 1965;62:372–375.
   PubMed Web of Science ®Google Scholar
• Farr AD. Treatment of haemophilia by transfusion: the first recorded case. J R Soc Med. 1981;74(4):301–305.
   PubMed Web of Science ®Google Scholar
• Wright AE. On a method of determining the condition of blood coagulability for clinical and experimental purposes, and on the effect of the administration of calcium salts in haemophilia and actual or threatened haemorrhage: preliminary communication. Br Med J. 1893;2(1700):223–225.
   PubMedGoogle Scholar
• Patek AJ, Taylor FH, Hemophilia II. Some properties of a substance obtained from normal human plasma effective in acceleration the coagulation of hemophilic blood. J Clin Invest. 1937;16(1):113–124.
   PubMedGoogle Scholar
• Pool JG, Shannon AE. Production of high-potency concentrates of antihemophilic globulin in a closed-bag system. N Engl J Med. 1965;273(27):1443–1447.
   PubMed Web of Science ®Google Scholar
• Morbidity and Mortality Weekly Report (MMWR). Pneumocystis carinii pneumonia among persons with hemophilia A. MMWR. 1982;31(27):365–367.
   PubMedGoogle Scholar
• Rouzioux C, Chamaret S, Montagnier L, et al. Absence of antibodies to AIDS virus in haemophiliacs treated with heat-treated factor VIII concentrate. Lancet. 1985;325(8423):271–272.
   Google Scholar
• Wood WI, Capon DJ, Simonsen CC, et al. Expression of active human factor VIII from recombinant DNA clones. Nature. 1984;312(5992):330–337.
   PubMed Web of Science ®Google Scholar
• Bray GL, Gomperts ED, Courter S, et al. A multicenter study of recombinant factor VIII (recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The Recombinate Study Group. Blood. 1994;83(9):2428–2435.
   PubMed Web of Science ®Google Scholar
• Fischer K, van der Bom JG, Molho P, et al. Prophylactic versus on-demand treatment strategies for severe haemophilia: a comparison of costs and long-term outcome. Haemophilia. 2002;8(6):745–752.
   PubMed Web of Science ®Google Scholar
• Gringeri A, Lundin B, von Mackensen S, et al. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT study). J Thromb Haemost. 2011;9(4):700–710.
   PubMed Web of Science ®Google Scholar
• Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535–544.
   PubMed Web of Science ®Google Scholar
• Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood. 2015;125(13):2038–2044.
   PubMed Web of Science ®Google Scholar
• Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe haemophilia. Blood. 2014;123(3):317–325.
   PubMed Web of Science ®Google Scholar
• Tiede A, Brand B, Fischer R, et al. Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with haemophilia A. J Thromb Haemost. 2013;11(4):670–678.
   PubMed Web of Science ®Google Scholar
• Coyle TE, Reding MT, Lin JC, et al. Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. J Thromb Haemost. 2014;12(4):488–496.
   PubMed Web of Science ®Google Scholar
• Konkle BA, Stasyshyn O, Chowdary P, et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015;126(9):1078–1085.
   PubMed Web of Science ®Google Scholar
• Powell JS, Pasi KJ, Ragni MV, et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med. 2013;369(24):2313–2323.
   PubMed Web of Science ®Google Scholar
• Negrier C, Knobe K, Tiede A, et al. Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B. Blood. 2011;118(10):2695–2701.
   PubMed Web of Science ®Google Scholar
• Collins PW, Møss J, Knobe K, et al. Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. J Thromb Haemost. 2012;10(11):2305–2312.
   PubMed Web of Science ®Google Scholar
• Santagostino E, Negrier C, Klamroth R, et al. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood. 2012;120(12):2405–2411.
   PubMed Web of Science ®Google Scholar
• Kitazawa T, Igawa T, Sampei Z, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med. 2012;18(10):1570–1574.
   PubMed Web of Science ®Google Scholar
• Sampei Z, Igawa T, Soeda T, et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One. 2013;8(2):e57479.
   PubMed Web of Science ®Google Scholar
• Shima M, Hanabusa H, Taki M, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 2016;374(21):2044–2053.
   PubMed Web of Science ®Google Scholar
• Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809–818.
   PubMed Web of Science ®Google Scholar
• Lenting PJ, Denis CV, Christophe OD. Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII? Blood. 2017 Oct 17;130:2463–2468.
   PubMed Web of Science ®Google Scholar
• Agersø H, Overgaard RV, Petersen MB, et al. Pharmacokinetics of an anti-TFPI monoclonal antibody (concizumab) blocking the TFPI interaction with the active site of FXa in Cynomolgus monkeys after iv and sc administration. Eur J Pharm Sci. 2014;56:65–69.
   PubMed Web of Science ®Google Scholar
• Chowdary P, Lethagen S, Friedrich U, et al. Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial. J Thromb Haemost. 2015;13(5):743–754.
   PubMed Web of Science ®Google Scholar
• Waters EK, Sigh J, Friedrich U, et al. Concizumab, an anti-tissue factor pathway inhibitor antibody, induces increased thrombin generation in plasma from haemophilia patients and healthy subjects measured by the thrombin generation assay. Haemophilia. 2017;23(5):769–776.
   PubMed Web of Science ®Google Scholar
• Pasi KJ, Rangarajan S, Georgiev P, et al. Targeting of antithrombin in hemophilia A or B with RNAi therapy. N Engl J Med. 2017;377(9):819–828.
   PubMed Web of Science ®Google Scholar
• Alnylam Pharmaceuticals Inc. Alnylam announces successful outcome following FDA type A meeting to discuss fitusiran program in hemophilia. 2017 Nov 9 [cited 2017 Nov 27]. Available from: http://investors.alnylam.com/releasedetail.cfm?ReleaseID=1048138
   Google Scholar
• Carr ME, Tortella BJ. Emerging and future therapies for hemophilia. J Blood Med. 2015;6:245–255.
   PubMed Web of Science ®Google Scholar
• Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365(25):2357–2365.
   PubMed Web of Science ®Google Scholar
• Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004.
   PubMed Web of Science ®Google Scholar
• George LA, Sullivan SK, Giermasz A, et al. SPK-9001: adeno-associated virus mediated gene transfer for hemophilia B achieves sustained mean factor IX activity levels of >30% without immunosuppression [abstract #91358]. Blood. 2016;128(22):3.
   Web of Science ®Google Scholar
• Rangarajan S, Walsh L, Lester W, et al. AAV5–factor VIII gene transfer in severe hemophilia A. N Engl J Med. 2017;377(26):2519–2530.
   Web of Science ®Google Scholar
• DiMichele DM. Hemophilia therapy–navigating speed bumps on the innovation highway. N Engl J Med. 2016;374(21):2087–2089.
   PubMed Web of Science ®Google Scholar
• Iorio A. Research and policy implications of a recently published controlled study in previously untreated haemophilia patients at high risk of inhibitor development. Haemophilia. 2017;23(3):350–352.
   PubMed Web of Science ®Google Scholar
• Peyvandi F, Mannucci PM, Palla R, et al. SIPPET: methodology, analysis and generalizability. Haemophilia. 2017;23(3):353–361.
   PubMed Web of Science ®Google Scholar
• Mannucci PM, Peyvandi F, Rosendaal FR. Reply to the letter by Iorio. Haemophilia. 2017;23(3):e248–e249.
   PubMedGoogle Scholar
• Marcucci M, Mancuso ME, Santagostino E, et al. Type and intensity of FVIII exposure on inhibitor development in PUPs with haemophilia A. A patient-level meta-analysis. Thromb Haemost. 2015;113(5):958–967.
   PubMed Web of Science ®Google Scholar
• Rosendaal FR, Palla R, Garagiola I, et al. Genetic risk stratification to reduce inhibitor development in the early treatment of hemophilia A: a SIPPET analysis. Blood. 2017;130(15):1757–1759.
   PubMed Web of Science ®Google Scholar
• Gouw SC, van der Bom JG, Ljung R, et al. Factor VIII products and inhibitor development in severe hemophilia A. N Engl J Med. 2013;368(3):231–239.
   PubMed Web of Science ®Google Scholar
• Calvez T, Chambost H, d’Oiron R, et al. Analyses of the FranceCoag cohort support immunogenicity differences among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A. Haematologica. 2017 Oct 12. [Epub ahead of print]. PII:haematol.2017.174706. DOI:10.3324/haematol.2017.174706
   PubMed Web of Science ®Google Scholar
• Chalmers EA, Brown SA, Keeling D, et al. Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. Haemophilia. 2007;13(2):149–155.
   PubMed Web of Science ®Google Scholar
• Mancuso ME, Mannucci PM, Rocino A, et al. Source and purity of factor VIII products as risk factors for inhibitor development in patients with hemophilia A. J Thromb Haemost. 2012;10(5):781–790.
   PubMed Web of Science ®Google Scholar
• Goudemand J, Rothschild C, Demiguel V, et al. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006;107(1):46–51.
   PubMed Web of Science ®Google Scholar
• Mannucci PM, Mancuso ME, Santagostino E. How we choose factor VIII to treat hemophilia. Blood. 2012;119(18):4108–4114.
   PubMed Web of Science ®Google Scholar
• Gouw SC, van der Bom JG, Marijke van den Berg H. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood. 2007;109(11):4648–4654.
   PubMed Web of Science ®Google Scholar
• Kurnik K, Bidlingmaier C, Engl W, et al. New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development. Haemophilia. 2010;16(2):256–262.
   PubMed Web of Science ®Google Scholar
• Messori A, Peyvandi F, Trippoli S, et al. High-titre inhibitors in previously untreated patients with severe haemophilia A receiving recombinant or plasma-derived factor VIII: a budget-impact analysis. Blood Transfus. 2017 May 15:1–7. [Epub ahead of print]. DOI:10.2450/2017.0352-16
   PubMedGoogle Scholar
• Wali B, Halimeh S, Male C. Economic considerations on the use of recombinant vs. plasmatic factor VIII in the treatment of previously untreated haemophilia A patients [abstract PSY50]. Value Health. 2016;19:A583.
   Web of Science ®Google Scholar
• Brackmann HH, Gormsen J. Massive factor-VIII infusion in Haemophiliac with factor-VIII inhibitor, high responder. 1977. Haemophilia. 2010;16(102):2–3.
   PubMedGoogle Scholar
• Brackmann HH, Oldenburg J, Schwaab R. Immune tolerance for the treatment of factor VIII inhibitors–twenty years’ ‘bonn protocol’. Vox Sang. 1996;70(Suppl 1):30–35.
   PubMedGoogle Scholar
• O’Day K, Runken C, Meyer K, et al. Economic impact of treating severe hemophilia A patients with plasma-derived factor VIII/VWF vs. recombinant factor VIII in the United States [abstract/poster PSY46]. Value Health. 2017;20(5):A216.
   Google Scholar
• Peyvandi F, Cannavò A, Garagiola I, et al. Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: a SIPPET analysis. J Thromb Haemost. 2017 Oct 28. [Epub ahead of print]. DOI:10.1111/jth.13888
   Web of Science ®Google Scholar
• Collins PW, Palmer BP, Chalmers E, et al. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000–2011. Blood. 2014;124(23):3389–3397.
   PubMed Web of Science ®Google Scholar
• Calvez T, Chambost H, Claeyssens-Donadel S, et al. Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A. Blood. 2014;124(23):3398–3408.
   PubMed Web of Science ®Google Scholar
• Fischer K, Lassila R, Peyvandi F, et al. Inhibitor development in haemophilia according to concentrate. Four-year results from the European HAemophilia Safety Surveillance (EUHASS) project. Thromb Haemost. 2015;113(5):968–975.
   PubMed Web of Science ®Google Scholar
• Gouw SC, van den Berg HM, Oldenburg J, et al. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis. Blood. 2012;119(12):2922–2934.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency. Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products. 2015 May 21 [cited 2017 Nov 27]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/06/WC500187409.pdf
   Google Scholar
• Kempton CL, Soucie JM, Abshire TC. Incidence of inhibitors in a cohort of 838 males with hemophilia A previously treated with factor VIII concentrates. J Thromb Haemost. 2006;4(12):2576–2581.
   PubMed Web of Science ®Google Scholar
• Blanchette VS, Key NS, Ljung LR, et al. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014;12(11):1935–1939.
   PubMed Web of Science ®Google Scholar
• Peyvandi F, Ettingshausen CE, Goudemand J, et al. New findings on inhibitor development: from registries to clinical studies. Haemophilia. 2017;23(Suppl 1):4–13.
   PubMedGoogle Scholar
• Kempton CL. Inhibitors in previously treated patients: a review of the literature. Haemophilia. 2010;16(102):61–65.
   PubMedGoogle Scholar
• White GC, DiMichele D, Mertens K, et al. Utilization of previously treated patients (PTPs), noninfected patients (NIPs), and previously untreated patients (PIPs) in the evaluation of new factor VIII and factor IX concentrates. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the international society on thrombosis and haemostasis. Thromb Haemost. 1999;81(3):462.
   PubMed Web of Science ®Google Scholar
• van den Berg HM. Epidemiological aspects of inhibitor development redefine the clinical importance of inhibitors. Haemophilia. 2014;20(Suppl 4):76–79.
   PubMedGoogle Scholar
• Xi M, Makris M, Marcucci M, et al. Inhibitor development in previously treated hemophilia A patients: a systematic review, meta-analysis, and meta-regression. J Thromb Haemost. 2013;11(9):1655–1662.
   PubMed Web of Science ®Google Scholar
• McMillan CW, Shapiro SS, Whitehurst D, et al. The natural history of factor VIII:C inhibitors in patients with hemophilia A: a national cooperative study. II. Observations on the initial development of factor VIII:C inhibitors. Blood. 1988;71(2):344–348.
   PubMed Web of Science ®Google Scholar
• Darby SC, Keeling DM, Spooner RJD, et al. The incidence of factor VIII and factor IX inhibitors in the hemophilia population of the UK and their effect on subsequent mortality, 1977–99. J Thromb Haemost. 2004;2(7):1047–1054.
   PubMed Web of Science ®Google Scholar
• Iorio A, Barbara AM, Makris M, et al. Natural history and clinical characteristics of inhibitors in previously treated haemophilia A patients: a case series. Haemophilia. 2017;23(2):255–263.
   PubMed Web of Science ®Google Scholar
• Collins PW, Chalmers E, Hart DP, et al. Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition). UK Haemophilia Centre Doctors Organization. Br J Haematol. 2013;160(2):153–170.
   PubMed Web of Science ®Google Scholar
• Ozelo M, Misgav M, Abdul Karim F, et al. Long-term patterns of safety and efficacy of bleeding prophylaxis with turoctocog alfa (NovoEight®) in previously treated patients with severe haemophilia A: interim results of the guardian™ 2 extension trial. Haemophilia. 2015;21(5):e436–e439.
   PubMed Web of Science ®Google Scholar
• Tiede A, Oldenburg J, Lissitchkov T, et al. Prophylaxis vs. on-demand treatment with Nuwiq® (Human-cl rhFVIII) in adults with severe haemophilia A. Haemophilia. 2016;22(3):374–380.
   PubMed Web of Science ®Google Scholar
• Rosendaal FR, Nieuwenhuis HK, van den Berg HM, et al. A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in The Netherlands. Dutch Hemophilia Study Group. Blood. 1993;81(8):2180–2186.
   PubMed Web of Science ®Google Scholar
• Peerlinck K, Arnout J, Gilles JG, et al. A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate. Thromb Haemost. 1993;69(2):115–118.
   PubMed Web of Science ®Google Scholar
• Matino D, Lillicrap D, Astermark J, et al. Switching clotting factor concentrates: considerations in estimating the risk of immunogenicity. Haemophilia. 2014;20(2):200–206.
   PubMed Web of Science ®Google Scholar
• Iorio A, Puccetti P, Makris M. Clotting factor concentrate switching and inhibitor development in hemophilia A. Blood. 2012;120(4):720–727.
   PubMed Web of Science ®Google Scholar
• US National Hemophilia Foundation, Medical and Scientific Advisory Council (MASAC). MASAC recommendations on standardized testing and surveillance for inhibitors in patients with hemophilia A and B (MASAC document #236). 2015 Aug 15 [Accessed 2017 Nov 27]. Available from: https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/MASAC-Recommendations/MASAC-Recommendations-on-Standardized-Testing-and-Surveillance-for-Inhibitors-in-Patients-with-Hemophilia-A-and-B
   Google Scholar