Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS)
Kathelijn Fischer, Riitta Lassila, Flora Peyvandi, A. Gatt, Samantha C. Gouw, Rob Hollingsworth, Thierry Lambert, Radek Kaczmarek, Diana Carbonero, Radek Kaczmarek, Diana Carbonero, Mike Makris, Cihan Ay, Christoph Male, Cedric Hermans, Peter Verhamme, Toshko Lissitchkov, Marios Antoniades, Miroslav Penka, Jan Blatny, Vladimir Komrska, Lone Hvitfeldt Poulsen, Peter Kampmann, Anna-Elina Lehtinen, Sophie Susen, Yesim Dargaud, Christine Biron, Roseline D'Oiron, Annie Harroche, Robert Klamroth, Johannes Oldenburg, Martina Buehrlen, Wolfgang Miesbach, Florian Langer, Patrick Spannag, Martin Oliveri, Helen Platokouki, Efrosyni Nomikou, Olga Katsarou, Vasileia Garypidou, Marina Economou, Laszlo Nemes, Beatrice Nolan, Niamh O'Connell, Radossi Paolo, Giancarlo Castaman, Flora Peyvandi, Flora Peyvandi, Angiola Rocino, Ezio Zanon, Annarita Tagliaferri, Giancarlo Agnelli, Raimondo De Crisotofaro, Piercarla Schinco, Alberto Tosetto, Sandra Lejniece, Neringa Gailiute, Alexander Gatt, Alexander Gatt, Anja Mäkelburg, Britta Laros-van Gorkom, Paul Brons, Frank W.G. Leebeek, Roger Schutgens, Jerzy Windyga, Cristina Catarino, Anabela Aires, Cristina Fraga, Sara Morais, Fernando Araújo, Margit Serban, Igor Davydkin, Angelika Batorova, Sasa Anzej Doma, Laura Segura Martinez, Angeles Palomo Bravo, Immaculada Soto Ortega, Santiago Bonanad, Fariba Baghaei, Jan Astermark, Margareta Holmström, Pierre Fontana, Markus Schmugge, Bulent Zulfikar, Kaan Kavakli, Mohammed Khan, Gary Benson, Will Lester, Page Andrew, Bagot Catherine, Fernando Pinto, Styliani Salta, Cathy Farrelly, Mary Matthias, Mike Laffan, Yee Thynn Thynn, Vickie Mcdonald, Steve Austin, Madan Bella, Charles Hay
Abstract
Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited. Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B. Methods: Inhibitor development in PTPs was collected since 2008 from 97 centers participating in European HAemophilia Safety Surveillance. Per concentrate, inhibitors were reported quarterly and the number of PTPs treated annually. Incidence rates (IRs)/1000 treatment years with 95% CIs were compared between concentrate types (plasma derived FVIII/FIX, standard half-life recombinant FVIII/FIX, and extended half-life recombinant (EHL-rFVIII/IX) concentrates using IR ratios with CI. Medians and IQRs were calculated for inhibitor characteristics. Results: < .01).For severe hemophilia B, inhibitor rate was 5/11,160 treatment years and IR was 0.45/1000 years (95% CI, 0.15-1.04), at median 3.7 years (95% CI, 2.1-42.4) and 260 EDs (95% CI, 130 to >1000). Data were insufficient to compare by type of FIX concentrates. Conclusion: Low inhibitor rates were observed for PTPs with severe hemophilia A and B. Data suggested reduced inhibitor development on EHL-rFVIII, but no significant difference between plasma-derived FVIII and standard half-life recombinant FVIII. FIX inhibitor rates were too low for robust statistical analysis.